<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04483011</url>
  </required_header>
  <id_info>
    <org_study_id>19RNHB(1918)</org_study_id>
    <nct_id>NCT04483011</nct_id>
  </id_info>
  <brief_title>The Safety and Efficacy Study of RiaGev in Healthy Adults</brief_title>
  <official_title>A Randomized, Double-blind, Comparator-controlled, Cross-over Study to Investigate the Safety and Efficacy of RiaGev™ in Healthy Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bioenergy Life Science, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>KGK Science Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Bioenergy Life Science, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This current randomized, double-blind, comparator-controlled, cross over study investigates&#xD;
      the efficacy and safety of RiaGev™ via evaluation of NAD+, ATP, glucose, insulin,&#xD;
      glutathione, and cortisol levels in healthy adults of ages 36-65.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Nicotinamide adenine dinucleotide (NAD+) is one of the essential cofactors required for the&#xD;
      proper function of living cells, and depletion in NAD has been correlated to aging&#xD;
      individuals as NAD is associated with oxidative stress and energy production. Per the&#xD;
      Population Reference Bureau (PRB), it is estimated that by the year 2060, the number of&#xD;
      Americans over the age of 65 will double to over 98 million. As well, over the years, there&#xD;
      has been a continuous rise in obesity within older Americans, reaching 44% for women and 36%&#xD;
      for men in the age range of 65-74. One of the most common chronic diseases that are&#xD;
      accompanied by aging and obesity diabetes. In 2016 the WHO reported that approximately 1.6&#xD;
      million deaths were attributed to diabetes. Half of these individuals had high blood glucose&#xD;
      before the age of 70. Hence it is crucial to actively control blood glucose and oxidative&#xD;
      stress during one's midlife stage.&#xD;
&#xD;
      The investigating product RiaGev™ is the first and only commercially available product that&#xD;
      contains Bioenergy Ribose® and vitamin B3. It increases NAD+ in the body efficiently to&#xD;
      promote healthy mitochondria, active immunity, and cholesterol reduction. As a result,&#xD;
      D-ribose is essential for healthy aging.&#xD;
&#xD;
      Bioenergy Ribose® is a 5-carbon carbohydrate (C5H10O5) called D-ribose designated as a&#xD;
      Generally Recognized as Safe (GRAS) substance by the US Food and Drug Administration (FDA).&#xD;
      It is produced via the pentose phosphate pathway (PPP), which is fundamental for adenosine&#xD;
      triphosphate (ATP) production. The PPP is a rate-limiting step that makes use of a short&#xD;
      supply enzyme called glucose-6-phosphate dehydrogenase (G-6-PDH). Supplementation of D-ribose&#xD;
      can bypass the PPP and directly contribute to ATP production. In addition, to its function&#xD;
      for ATP production D-ribose is a critical element of deoxyribonucleic acid (DNA), ribonucleic&#xD;
      acid (RNA), and acetyl coenzyme A. Provided there is a reduction in ATP production; aging is&#xD;
      frequently due to a decline in mitochondria function. Hence, cell function and integrity are&#xD;
      compromised, leading to chronic cardiovascular conditions and fatigue (6). With active&#xD;
      D-ribose supplementation, improvements have been noted in several pathological conditions&#xD;
      such as chronic fatigue syndrome, fibromyalgia, and myocardial dysfunction. Furthermore,&#xD;
      D-ribose demonstrated improvements in athletic performances by recovering ATP levels and&#xD;
      repairing cellular damage.&#xD;
&#xD;
      Vitamin B3 is an essential water-soluble vitamin known as either niacin, nicotinic acid, or&#xD;
      nicotinamide. It is found in foods such as chicken, beef, fish, nuts, legumes, and grains.&#xD;
      Also, vitamin B3 can be obtained from conversions of tryptophan in the body. Therefore, foods&#xD;
      with tryptophan such as milk, eggs, meat, and fish are another great source of vitamin B3.&#xD;
      Once vitamin B3 is consumed, it is converted into two different active forms called NAD+ or&#xD;
      nicotinamide adenine dinucleotide phosphate (NADP). NAD+ and NADP are essential for various&#xD;
      metabolic redox processes with oxidized or reduced substrates. Cellular functions like genome&#xD;
      integrity, gene expression, and cellular communication are carried out by NAD+ required&#xD;
      enzymes. These required enzymes are also crucial for the production of ATP via energy&#xD;
      transfer from carbohydrates, fats, and proteins. NADP is involved in fewer reactions than&#xD;
      NAD+ such as cholesterol and fatty acid synthesis along with antioxidation. Lack of NAD+ has&#xD;
      been associated with a variety of aging-related conditions such as metabolic syndrome,&#xD;
      cardiovascular health, and cancer.&#xD;
&#xD;
      This current randomized, double-blind, comparator-controlled, cross over study will&#xD;
      investigate the efficacy and safety of RiaGev™ via evaluation of NAD+, glucose, insulin,&#xD;
      glutathione, and cortisol levels in healthy adults of ages 36-65.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">October 25, 2019</start_date>
  <completion_date type="Anticipated">November 30, 2020</completion_date>
  <primary_completion_date type="Actual">July 30, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>randomized, double-blind, comparator-controlled, cross-over</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Whole Blood NAD+ Level Change Over Baseline After Supplementation</measure>
    <time_frame>Day 1 to Day 8</time_frame>
    <description>Whole blood NAD+ concentration are measured at Day 1, Day 3, Day 5, and Day 8. A NAD+ Level change over baseline (Day 1) is calculated by subtracting the NAD+ level at Day 1 ( e.g Day 5 over Day 1 = Day 5 - Day 1). The significance of change (p value) is calculated comparing within RiaGev or Comparator group, and between RiaGev and Comparator groups.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Whole Blood NADP+ Level Change Over Baseline After Supplementation</measure>
    <time_frame>Day 1 to Day 8</time_frame>
    <description>Whole blood NADP+ concentration are measured at Day 1, Day 3, Day 5, and Day 8. NADP+ level changes over baseline (Day 1) are calculated by substracting NADP+ level at Day 1. The significance of change (p values) are calculated comparing changes within and between RiaGev and Comparator groups.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Whole Blood NAD+ Plus NADP+ Level Change Over Baseline</measure>
    <time_frame>Day 1 to 8</time_frame>
    <description>The change in whole blood NAD+ plus NADP+ levels from Day 1 baseline to Day 8 when supplemented with RiaGev™ or comparator. The parameter is measured at Day 1, Day 3, Day 5, and Day 8. A change over baseline is calculated by subtracting Day 1 value. The significance of changes (p value) are calculated by comparing within and between RiaGev and Comparator groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum Glucose Change After RiaGev Supplementation Assessed by OGTT</measure>
    <time_frame>7 days</time_frame>
    <description>The serum glucose as assessed by a standard Oral Glucose Tolerance Test (OGTT) on Day 1 and on Day 8 after 7-day supplementation with either RiaGev™ or comparator. Incremental Area Under the Curve (iAUC) is used as overall blood glucose. Serum glucose change is calculated by subtracting iAUC on Day 1 from iAUC on Day 8. The significance of change (p value) is calculated by comparing values on Day 8 and Day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Insulin Change After RiaGev Supplementation Assessed by OGTT</measure>
    <time_frame>7 days</time_frame>
    <description>Serum insulin is assessed by a standard Oral Glucose Tolerance Test (OGTT) on Day 1 and Day 8 after 7-day supplementation with either RiaGev™ or comparator. Serum insulin change is calculated by substracting its level on Day 1 from Day 8. The significance of change (p value) is calculated by comparing Day 1 and Day 8.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Glutathione (GSH + GSSG) Change Over Baseline After RiaGev Supplementation</measure>
    <time_frame>7 days</time_frame>
    <description>Total serum Glutathione (GSH + GSSG) is measured on Day 1, Day 3, Day 5 and Day 8. after a 7-day supplementation with either RiaGev™ or comparator. A change over baseline is calculated by subtracting glutathione level on Day 1 baseline (e g Day 5 over Day 1 = Day 5 - Day 1). The significance of change (p value) is calculated within the RiaGev or Comparator group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum High Energy Phosphate (ATP + ADP) Concentration After RiaGev Supplementation</measure>
    <time_frame>7 days</time_frame>
    <description>Serum high energy phosphate (ATP + ADP) after a 7-day supplementation with either RiaGev™ or comparator. The measurement take place on Day 1, Day 3, Day 5, and Day 8. Comparison are made between the two groups. The significance (p value) is also calculated between the groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Waking Salivary Cortisol Level After RiaGev Supplementation</measure>
    <time_frame>7 days</time_frame>
    <description>The salivary cortisol level after a 7-day supplementation with either RiaGev™ or comparator. The measurement take place on Day 1, 3, 5, and 8. The salivary cortisol level as well as change of salivary cortisol level over baseline (Day 1) are reported. Comparisons are make both between the RiaGev and Comparison groups as well as within RiaGev group against its Day 1 baseline. The corresponding significance (p value) will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Change in Checklist Individual Strength (CIS) Questionnaire Outcome After a 7-day Supplementation With Either RiaGev™ or Comparator.</measure>
    <time_frame>7 days</time_frame>
    <description>Checklist Individual Strength (CIS) Questionnaire was designed by the Dutch research team of Vercoulen et el, to measure fatigues. A standard CIS Questionnaire contains 20 questions, each scoring 1 to 7, total score 20 - 140, with higher score indicating more tiredness. Thus, a negative value in changing score (such as Day 5 - Day 1 baseline) means reduction of tiredness and verse versa.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator</measure>
    <time_frame>7 days</time_frame>
    <description>The number of out-of-norm incidence (as indicator of safety) will be reported. Clinical chemistry parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, electrolytes (Na, K, Cl), fasting glucose. When a parameter is within normal limit, it will been reported as 0 out-of-norm.</description>
  </other_outcome>
  <other_outcome>
    <measure>The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator.</measure>
    <time_frame>7 days</time_frame>
    <description>The number of out-of-norm hematology parameter incidence (as indicator of safety) will be reported. Hematology parameters include white blood cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), red blood cell (RBC) count, hemoglobin, hematocrit, platelet count, RBC indices (mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW). When a parameter is within normal limits, it is reported as 0 out-of-norm.</description>
  </other_outcome>
  <other_outcome>
    <measure>The Number of Out-of-norm Vital Signs When Supplemented With RiaGev or Comparator</measure>
    <time_frame>7 days</time_frame>
    <description>Vital signs include blood pressure (BP) and heart rate (HR). The number of out-of-norm incidence will be reported. When a parameter is within normal limits, it is reported as 0 out-of-norm.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Metabolic Syndrome</condition>
  <condition>Premature Aging</condition>
  <arm_group>
    <arm_group_label>RiaGev</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RiaGev, 2000mg, BID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Comparator</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Comparator matched to RiaGev, BID</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>RiaGev</intervention_name>
    <description>Dietary supplementation</description>
    <arm_group_label>Comparator</arm_group_label>
    <arm_group_label>RiaGev</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy male and females between the ages of 35 and 65 years of age, inclusive&#xD;
&#xD;
          2. BMI between 18.5 to 29.9 kg/m2, inclusive&#xD;
&#xD;
          3. Female participant is not of child-bearing potential, defined as females who have&#xD;
             undergone a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy,&#xD;
             bilateral tubal ligation, complete endometrial ablation) or have been post-menopausal&#xD;
             (natural or surgically) for at least 1 year prior to screening&#xD;
&#xD;
             Or,&#xD;
&#xD;
             Females of child-bearing potential must have a negative urine pregnancy test at&#xD;
             screening and baseline and agree to use a medically approved method of birth control&#xD;
             for the duration of the study. All hormonal birth control must have been in use for a&#xD;
             minimum of three months. Acceptable methods of birth control include:&#xD;
&#xD;
               -  Hormonal contraceptives including oral contraceptives, hormone birth control&#xD;
                  patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable&#xD;
                  contraceptives (Depo-Provera, Lunelle), or hormone implant (Norplant System)&#xD;
&#xD;
               -  Double-barrier method&#xD;
&#xD;
               -  Intrauterine devices&#xD;
&#xD;
               -  Non-heterosexual lifestyle or agrees to use contraception if planning on changing&#xD;
                  to heterosexual partner(s)&#xD;
&#xD;
               -  Vasectomy of partner at least 6 months prior to screening&#xD;
&#xD;
          4. Healthy as determined by laboratory results, medical history, physical exam and EKG&#xD;
&#xD;
          5. Agrees to avoid supplementation with tryptophan and vitamin B3 or its derivatives&#xD;
             (niacin, nicotinic acid, niacinamide) one week prior to randomization and during the&#xD;
             study&#xD;
&#xD;
          6. Ability to complete maximal and submaximal exercise tests&#xD;
&#xD;
          7. Agrees to maintain current diet and activity level throughout the study&#xD;
&#xD;
          8. Agrees to comply to all study procedures&#xD;
&#xD;
          9. Has given voluntary, written, informed consent to participate in the study&#xD;
&#xD;
         10. Self-reported good sleeper at screening. Have a regular sleep cycle with a bedtime&#xD;
             between the approximate hours of 9:00pm and 12:00am and regularly receive between 7-9&#xD;
             hours of sleep, and agrees to maintain this sleep schedule throughout the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Women who are pregnant, breast feeding, or planning to become pregnant during the&#xD;
             trial&#xD;
&#xD;
          2. Allergy or sensitivity to investigational product's ingredients or standard meal&#xD;
             provided&#xD;
&#xD;
          3. Current or ex-smokers within the past year&#xD;
&#xD;
          4. Major surgery within the past 3 months which may impact the study outcomes to be&#xD;
             assessed by the QI.&#xD;
&#xD;
          5. Untreated/unresolved/uncontrolled cardiovascular disease. Participants with no&#xD;
             significant cardiovascular event in the past 1 year and on stable medication may be&#xD;
             included after assessment by the QI on a case by case basis&#xD;
&#xD;
          6. Self reported current or pre-existing thyroid condition. Treatment on a stable dose&#xD;
             medication for over 3 months will be reviewed on a case-by-case basis by the QI&#xD;
&#xD;
          7. Current or history of hypertension.&#xD;
&#xD;
          8. Type I or Type II diabetes&#xD;
&#xD;
          9. Cancer, except skin cancers completely excised with no chemotherapy or radiation with&#xD;
             a follow up that is negative. Volunteers with cancer in full remission for more than&#xD;
             five years after diagnosis are acceptable&#xD;
&#xD;
         10. Self reported of any autoimmune disease or immune-compromised&#xD;
&#xD;
         11. Self reported by subjects of being HIV or Hepatitis B/C positive&#xD;
&#xD;
         12. History or currently with kidney and liver diseases assessed by QI on a case by case&#xD;
             basis, with the exception of history of kidney stones symptom free for 1 year&#xD;
&#xD;
         13. Known medical or psychological condition that, in the qualified investigator's&#xD;
             opinion, could interfere with study participation&#xD;
&#xD;
         14. Significant gastrointestinal disease (examples include but are not limited to Celiac&#xD;
             disease and inflammatory bowel disease)&#xD;
&#xD;
         15. Self reported of bleeding disorders.&#xD;
&#xD;
         16. Current diagnosis of gout within past three months as per the QI's assessment&#xD;
&#xD;
         17. Clinically significant abnormal laboratory results at screening as assessed by QI&#xD;
&#xD;
         18. Current use of prescribed medications or over the counter supplements that may&#xD;
             interfere with the IP assessed by QI (See Section 7.3)&#xD;
&#xD;
         19. Alcohol consumption of &gt;2 standard drinks/day or &gt;14 drinks/week&#xD;
&#xD;
         20. Alcohol or drug abuse within the past 12 months&#xD;
&#xD;
         21. Use of medical marijuana&#xD;
&#xD;
         22. Frequent use of recreational drugs within 6 months of baseline assessed as per QI&#xD;
&#xD;
         23. Planned blood donation during or within 30 days following conclusion of clinical trial&#xD;
&#xD;
         24. Participation in other clinical research trials 30 days prior to baseline&#xD;
&#xD;
         25. Participants that are cognitively impaired and/or who are unable to give informed&#xD;
             consent&#xD;
&#xD;
         26. Any other active or unstable medical condition, that, in the opinion of the QI, may&#xD;
             adversely affect the participant's ability to complete the study or its measures or&#xD;
             pose significant risk to the participant.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>36 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Malkanthi Evans, Ph.D</last_name>
    <role>Study Chair</role>
    <affiliation>KGK Science Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Trisha Shamp, PA-C, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Prism Research, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Prism Research, Inc.</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>July 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <results_first_submitted>September 9, 2020</results_first_submitted>
  <results_first_submitted_qc>November 24, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 25, 2020</results_first_posted>
  <last_update_submitted>November 24, 2020</last_update_submitted>
  <last_update_submitted_qc>November 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NAD+</keyword>
  <keyword>ATP</keyword>
  <keyword>Glutathione</keyword>
  <keyword>Cortisol</keyword>
  <keyword>Exercise</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Aging, Premature</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 24, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/11/NCT04483011/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 7, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/11/NCT04483011/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Total of 42 subject screened, 18 enrolled into study and randomized into two groups with 9 subjects each.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>RiaGev, Then Comparator</title>
          <description>RiaGev, 2000mg, BID, in Intervention Period 1, then 7 day washout, then cross-over to Comparator in Intervention Period 2</description>
        </group>
        <group group_id="P2">
          <title>Comparator, Then RiaGev</title>
          <description>Comparator, BID, in Intervention Period 1, then 7 day washout, then cross-over to RiaGev 2000mg BID in Intervention Period 2</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Intervention Period 1 (8 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout (7 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Intervention Period 2 (8 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>RiaGev, Then Comarator</title>
          <description>RiaGev, 2000mg, BID, in Period 1, then cross-over to Comparator in Period 2, after 7-day washout.</description>
        </group>
        <group group_id="B2">
          <title>Comparator, Then RiaGev</title>
          <description>Comparator, BID, in Period 1, then cross-over to RiaGev 2000mg, BID, in Period 2 after 7-day washout.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="18"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50.11" spread="8.62"/>
                    <measurement group_id="B2" value="53.33" spread="7.31"/>
                    <measurement group_id="B3" value="51.72" spread="7.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>Kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="75.15" spread="14.60"/>
                    <measurement group_id="B2" value="79.06" spread="19.99"/>
                    <measurement group_id="B3" value="77.11" spread="17.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>CM</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="175.22" spread="8.12"/>
                    <measurement group_id="B2" value="172.67" spread="14.18"/>
                    <measurement group_id="B3" value="173.95" spread="11.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>Kg/cm^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24.29" spread="2.96"/>
                    <measurement group_id="B2" value="26.12" spread="2.75"/>
                    <measurement group_id="B3" value="25.21" spread="2.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Systolic Blood Pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="124.57" spread="13.01"/>
                    <measurement group_id="B2" value="124.26" spread="9.32"/>
                    <measurement group_id="B3" value="124.42" spread="11.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diastolic Blood Pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="78.33" spread="7.63"/>
                    <measurement group_id="B2" value="78.31" spread="5.01"/>
                    <measurement group_id="B3" value="78.32" spread="6.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Heart Rate</title>
          <units>bpm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.11" spread="19.62"/>
                    <measurement group_id="B2" value="66.33" spread="9.11"/>
                    <measurement group_id="B3" value="65.22" spread="14.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Whole Blood NAD+ Level Change Over Baseline After Supplementation</title>
        <description>Whole blood NAD+ concentration are measured at Day 1, Day 3, Day 5, and Day 8. A NAD+ Level change over baseline (Day 1) is calculated by subtracting the NAD+ level at Day 1 ( e.g Day 5 over Day 1 = Day 5 - Day 1). The significance of change (p value) is calculated comparing within RiaGev or Comparator group, and between RiaGev and Comparator groups.</description>
        <time_frame>Day 1 to Day 8</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>RiaGev</title>
            <description>RiaGev, 2000mg, BID&#xD;
RiaGev: Dietary supplementation</description>
          </group>
          <group group_id="O2">
            <title>Comparator</title>
            <description>Comparator matched to RiaGev, BID&#xD;
Comparator: Dietary ingredients</description>
          </group>
        </group_list>
        <measure>
          <title>Whole Blood NAD+ Level Change Over Baseline After Supplementation</title>
          <description>Whole blood NAD+ concentration are measured at Day 1, Day 3, Day 5, and Day 8. A NAD+ Level change over baseline (Day 1) is calculated by subtracting the NAD+ level at Day 1 ( e.g Day 5 over Day 1 = Day 5 - Day 1). The significance of change (p value) is calculated comparing within RiaGev or Comparator group, and between RiaGev and Comparator groups.</description>
          <population>ITT</population>
          <units>MicroMolar</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 3 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.23" spread="3.39"/>
                    <measurement group_id="O2" value="0.13" spread="4.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.12" spread="4.72"/>
                    <measurement group_id="O2" value="-0.20" spread="2.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.30" spread="3.20"/>
                    <measurement group_id="O2" value="-0.60" spread="2.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>A comparison between before and after RiaGev supplementation.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.034</p_value>
            <p_value_desc>&lt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>2.12</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>4.72</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value in RiaGev group at Day 5 over Dave 1 is reported.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A comparison between before and after supplementation of Comparator.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.265</p_value>
            <p_value_desc>p &gt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.20</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>2.79</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value in Comparator group at Day 5 over Day 1 is reported.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A comparison between RiaGev and Comparator groups.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.044</p_value>
            <p_value_desc>&lt; 0.05</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>2.12</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>4.72</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value between RiaGev and Comparator groups at Day 5 over Day 1 is reported.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Whole Blood NADP+ Level Change Over Baseline After Supplementation</title>
        <description>Whole blood NADP+ concentration are measured at Day 1, Day 3, Day 5, and Day 8. NADP+ level changes over baseline (Day 1) are calculated by substracting NADP+ level at Day 1. The significance of change (p values) are calculated comparing changes within and between RiaGev and Comparator groups.</description>
        <time_frame>Day 1 to Day 8</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>RiaGev</title>
            <description>RiaGev, 2000mg, BID&#xD;
RiaGev: Dietary supplementation</description>
          </group>
          <group group_id="O2">
            <title>Comparator</title>
            <description>Comparator matched to RiaGev, BID&#xD;
RiaGev: Dietary supplementation</description>
          </group>
        </group_list>
        <measure>
          <title>Whole Blood NADP+ Level Change Over Baseline After Supplementation</title>
          <description>Whole blood NADP+ concentration are measured at Day 1, Day 3, Day 5, and Day 8. NADP+ level changes over baseline (Day 1) are calculated by substracting NADP+ level at Day 1. The significance of change (p values) are calculated comparing changes within and between RiaGev and Comparator groups.</description>
          <population>ITT</population>
          <units>microMolar</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 3 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.30" spread="1.72"/>
                    <measurement group_id="O2" value="0.85" spread="2.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.88" spread="2.55"/>
                    <measurement group_id="O2" value="0.51" spread="1.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.33" spread="1.88"/>
                    <measurement group_id="O2" value="0.34" spread="1.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>A comparison between before and after supplementation of RiaGev.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.008</p_value>
            <p_value_desc>p &lt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>1.33</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>1.88</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value in RiaGev group at Day 5 over Day 1 is reported.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A comparison between before and after supplementation with Comparator.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.297</p_value>
            <p_value_desc>p &gt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.34</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>1.34</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value in Comparator group at Day 5 over Day 1 is reported.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A comparison between RiaGev and Comparator supplementation.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.04</p_value>
            <p_value_desc>p &lt; 0.05</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>1.33</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>1.88</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value between RiaGev and Comparator groups at Day 5 over Day 1 is reported.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Whole Blood NAD+ Plus NADP+ Level Change Over Baseline</title>
        <description>The change in whole blood NAD+ plus NADP+ levels from Day 1 baseline to Day 8 when supplemented with RiaGev™ or comparator. The parameter is measured at Day 1, Day 3, Day 5, and Day 8. A change over baseline is calculated by subtracting Day 1 value. The significance of changes (p value) are calculated by comparing within and between RiaGev and Comparator groups.</description>
        <time_frame>Day 1 to 8</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>RiaGev</title>
            <description>RiaGev, 2000mg, BID&#xD;
RiaGev: Dietary supplementation</description>
          </group>
          <group group_id="O2">
            <title>Comparator</title>
            <description>Comparator matched to RiaGev, BID&#xD;
Comparator: Dietary ingredient</description>
          </group>
        </group_list>
        <measure>
          <title>Whole Blood NAD+ Plus NADP+ Level Change Over Baseline</title>
          <description>The change in whole blood NAD+ plus NADP+ levels from Day 1 baseline to Day 8 when supplemented with RiaGev™ or comparator. The parameter is measured at Day 1, Day 3, Day 5, and Day 8. A change over baseline is calculated by subtracting Day 1 value. The significance of changes (p value) are calculated by comparing within and between RiaGev and Comparator groups.</description>
          <population>ITT population</population>
          <units>microMolar</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 3 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.54" spread="4.60"/>
                    <measurement group_id="O2" value="0.97" spread="7.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.01" spread="6.57"/>
                    <measurement group_id="O2" value="0.40" spread="3.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.63" spread="4.30"/>
                    <measurement group_id="O2" value="-0.24" spread="3.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>A comparison between before and after RiaGev supplementation.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.004</p_value>
            <p_value_desc>p &lt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>4.01</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>6.57</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value in the RiaGev group at Day 5 over Day 1 is reported.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A comparison between before and after supplementation with Comparator.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.640</p_value>
            <p_value_desc>p &gt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.40</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>3.88</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value in Comparator group at Day 5 over Day 1 is reported.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A comparison between RiaGev and Comparator supplementation.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.014</p_value>
            <p_value_desc>p &lt; 0.05</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>4.01</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>6.57</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value between RiaGev and Comparator groups at Day 5 over Day 1 is reported.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum Glucose Change After RiaGev Supplementation Assessed by OGTT</title>
        <description>The serum glucose as assessed by a standard Oral Glucose Tolerance Test (OGTT) on Day 1 and on Day 8 after 7-day supplementation with either RiaGev™ or comparator. Incremental Area Under the Curve (iAUC) is used as overall blood glucose. Serum glucose change is calculated by subtracting iAUC on Day 1 from iAUC on Day 8. The significance of change (p value) is calculated by comparing values on Day 8 and Day 1.</description>
        <time_frame>7 days</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>RiaGev</title>
            <description>RiaGev, 2000mg, BID&#xD;
RiaGev: Dietary supplementation</description>
          </group>
          <group group_id="O2">
            <title>Comparator</title>
            <description>Comparator matched to RiaGev, BID&#xD;
Comparator: Dietary ingredients</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Glucose Change After RiaGev Supplementation Assessed by OGTT</title>
          <description>The serum glucose as assessed by a standard Oral Glucose Tolerance Test (OGTT) on Day 1 and on Day 8 after 7-day supplementation with either RiaGev™ or comparator. Incremental Area Under the Curve (iAUC) is used as overall blood glucose. Serum glucose change is calculated by subtracting iAUC on Day 1 from iAUC on Day 8. The significance of change (p value) is calculated by comparing values on Day 8 and Day 1.</description>
          <population>ITT population</population>
          <units>(mg/dL)*min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17700.42" spread="2525.30"/>
                    <measurement group_id="O2" value="876.25" spread="1601.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="662.50" spread="2031.70"/>
                    <measurement group_id="O2" value="574.17" spread="1640.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Day 1 to Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1037.92" spread="1590.74"/>
                    <measurement group_id="O2" value="-302.08" spread="1427.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>A comparison before and after RiaGev supplementation.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.013</p_value>
            <p_value_desc>p &lt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-1037.92</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>1590.74</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value in RiaGev group at Day 8 over Day 1 is reported.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A comparison before before and after supplementation with Comparator.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.382</p_value>
            <p_value_desc>p &gt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-302.08</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>1427.42</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value in Comparator group at Day 8 over Day 1 is reported.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum Insulin Change After RiaGev Supplementation Assessed by OGTT</title>
        <description>Serum insulin is assessed by a standard Oral Glucose Tolerance Test (OGTT) on Day 1 and Day 8 after 7-day supplementation with either RiaGev™ or comparator. Serum insulin change is calculated by substracting its level on Day 1 from Day 8. The significance of change (p value) is calculated by comparing Day 1 and Day 8.</description>
        <time_frame>7 days</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>RiaGev</title>
            <description>RiaGev, 2000mg, BID&#xD;
RiaGev: Dietary supplementation</description>
          </group>
          <group group_id="O2">
            <title>Comparator</title>
            <description>Comparator matched to RiaGev, BID&#xD;
Comparator: Dietary ingredients</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Insulin Change After RiaGev Supplementation Assessed by OGTT</title>
          <description>Serum insulin is assessed by a standard Oral Glucose Tolerance Test (OGTT) on Day 1 and Day 8 after 7-day supplementation with either RiaGev™ or comparator. Serum insulin change is calculated by substracting its level on Day 1 from Day 8. The significance of change (p value) is calculated by comparing Day 1 and Day 8.</description>
          <population>ITT population</population>
          <units>(microUnit/mL)*min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4807.42" spread="2419.04"/>
                    <measurement group_id="O2" value="4545.67" spread="1915.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4672.29" spread="2427.27"/>
                    <measurement group_id="O2" value="4410.88" spread="1929.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Day 1 to Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-135.13" spread="2153.66"/>
                    <measurement group_id="O2" value="-134.79" spread="1830.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>A comparison between before and after RiaGev supplementation</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.793</p_value>
            <p_value_desc>p &gt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-135.13</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>2153.66</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value in RiaGev group at Day 8 over Day 1 baseline is reported.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A comparison between before and after supplementation with Comparator.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.758</p_value>
            <p_value_desc>p &gt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-134.79</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>1830.16</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value in Comparator group at Day 8 over Day 1 baseline is reported.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum Glutathione (GSH + GSSG) Change Over Baseline After RiaGev Supplementation</title>
        <description>Total serum Glutathione (GSH + GSSG) is measured on Day 1, Day 3, Day 5 and Day 8. after a 7-day supplementation with either RiaGev™ or comparator. A change over baseline is calculated by subtracting glutathione level on Day 1 baseline (e g Day 5 over Day 1 = Day 5 - Day 1). The significance of change (p value) is calculated within the RiaGev or Comparator group.</description>
        <time_frame>7 days</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>RiaGev</title>
            <description>RiaGev, 2000mg, BID&#xD;
RiaGev: Dietary supplementation</description>
          </group>
          <group group_id="O2">
            <title>Comparator</title>
            <description>Comparator matched to RiaGev, BID&#xD;
Comparator: Dietary ingredient</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Glutathione (GSH + GSSG) Change Over Baseline After RiaGev Supplementation</title>
          <description>Total serum Glutathione (GSH + GSSG) is measured on Day 1, Day 3, Day 5 and Day 8. after a 7-day supplementation with either RiaGev™ or comparator. A change over baseline is calculated by subtracting glutathione level on Day 1 baseline (e g Day 5 over Day 1 = Day 5 - Day 1). The significance of change (p value) is calculated within the RiaGev or Comparator group.</description>
          <population>ITT</population>
          <units>microMolar</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 3 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.85" spread="124.73"/>
                    <measurement group_id="O2" value="32.43" spread="130.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.20" spread="123.89"/>
                    <measurement group_id="O2" value="15.55" spread="88.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.55" spread="66.82"/>
                    <measurement group_id="O2" value="-15.08" spread="76.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>A comparison between before and after RiaGev supplementation</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.003</p_value>
            <p_value_desc>p &lt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>70.20</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>123.89</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value in RiaGev group at Day 5 over Day 1 is reported.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A comparison between before and after supplementation with Comparator.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.766</p_value>
            <p_value_desc>p &gt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>15.55</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>88.62</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value in Comparator group at Day 5 over Day 1 is reported.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum High Energy Phosphate (ATP + ADP) Concentration After RiaGev Supplementation</title>
        <description>Serum high energy phosphate (ATP + ADP) after a 7-day supplementation with either RiaGev™ or comparator. The measurement take place on Day 1, Day 3, Day 5, and Day 8. Comparison are made between the two groups. The significance (p value) is also calculated between the groups.</description>
        <time_frame>7 days</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>RiaGev</title>
            <description>RiaGev, 2000mg, BID&#xD;
RiaGev: Dietary supplementation</description>
          </group>
          <group group_id="O2">
            <title>Comparator</title>
            <description>Comparator matched to RiaGev, BID&#xD;
Comparator: Dietary ingredient</description>
          </group>
        </group_list>
        <measure>
          <title>Serum High Energy Phosphate (ATP + ADP) Concentration After RiaGev Supplementation</title>
          <description>Serum high energy phosphate (ATP + ADP) after a 7-day supplementation with either RiaGev™ or comparator. The measurement take place on Day 1, Day 3, Day 5, and Day 8. Comparison are made between the two groups. The significance (p value) is also calculated between the groups.</description>
          <population>ITT</population>
          <units>microMolar</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 (baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="327.10" spread="42.87"/>
                    <measurement group_id="O2" value="324.94" spread="58.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="351.18" spread="75.71"/>
                    <measurement group_id="O2" value="345.98" spread="102.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="353.28" spread="82.03"/>
                    <measurement group_id="O2" value="329.27" spread="94.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="330.40" spread="41.89"/>
                    <measurement group_id="O2" value="326.20" spread="45.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A comparison between RiaGev and Comparator groups after 7-day supplementation.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.029</p_value>
            <p_value_desc>p &lt; 0.05</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>24.01</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>58.20</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value between RiaGev and Comparator groups at Day 5 is reported.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Waking Salivary Cortisol Level After RiaGev Supplementation</title>
        <description>The salivary cortisol level after a 7-day supplementation with either RiaGev™ or comparator. The measurement take place on Day 1, 3, 5, and 8. The salivary cortisol level as well as change of salivary cortisol level over baseline (Day 1) are reported. Comparisons are make both between the RiaGev and Comparison groups as well as within RiaGev group against its Day 1 baseline. The corresponding significance (p value) will be calculated.</description>
        <time_frame>7 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>RiaGev</title>
            <description>RiaGev, 2000mg, BID&#xD;
RiaGev: Dietary supplementation</description>
          </group>
          <group group_id="O2">
            <title>Comparator</title>
            <description>Comparator matched to RiaGev, BID&#xD;
Comparator: Dietary ingredient</description>
          </group>
        </group_list>
        <measure>
          <title>The Waking Salivary Cortisol Level After RiaGev Supplementation</title>
          <description>The salivary cortisol level after a 7-day supplementation with either RiaGev™ or comparator. The measurement take place on Day 1, 3, 5, and 8. The salivary cortisol level as well as change of salivary cortisol level over baseline (Day 1) are reported. Comparisons are make both between the RiaGev and Comparison groups as well as within RiaGev group against its Day 1 baseline. The corresponding significance (p value) will be calculated.</description>
          <units>mcg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 (baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.43" spread="0.15"/>
                    <measurement group_id="O2" value="0.51" spread="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.40" spread="0.19"/>
                    <measurement group_id="O2" value="0.47" spread="0.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.41" spread="0.32"/>
                    <measurement group_id="O2" value="0.57" spread="0.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.38" spread="0.18"/>
                    <measurement group_id="O2" value="0.51" spread="0.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" spread="0.18"/>
                    <measurement group_id="O2" value="-0.04" spread="0.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.02" spread="0.34"/>
                    <measurement group_id="O2" value="0.07" spread="0.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.05" spread="0.19"/>
                    <measurement group_id="O2" value="0.00" spread="0.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A comparison between RiaGev and Comparator groups.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.034</p_value>
            <p_value_desc>p &lt; 0.05</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.16</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>0.32</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value between RiaGev and Comparator groups at Day 5 is reported.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Change in Checklist Individual Strength (CIS) Questionnaire Outcome After a 7-day Supplementation With Either RiaGev™ or Comparator.</title>
        <description>Checklist Individual Strength (CIS) Questionnaire was designed by the Dutch research team of Vercoulen et el, to measure fatigues. A standard CIS Questionnaire contains 20 questions, each scoring 1 to 7, total score 20 - 140, with higher score indicating more tiredness. Thus, a negative value in changing score (such as Day 5 - Day 1 baseline) means reduction of tiredness and verse versa.</description>
        <time_frame>7 days</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>RiaGev</title>
            <description>RiaGev, 2000mg, BID&#xD;
RiaGev: Dietary supplementation</description>
          </group>
          <group group_id="O2">
            <title>Comparator</title>
            <description>Comparator matched to RiaGev, BID&#xD;
Comparator: Dietary ingredient</description>
          </group>
        </group_list>
        <measure>
          <title>The Change in Checklist Individual Strength (CIS) Questionnaire Outcome After a 7-day Supplementation With Either RiaGev™ or Comparator.</title>
          <description>Checklist Individual Strength (CIS) Questionnaire was designed by the Dutch research team of Vercoulen et el, to measure fatigues. A standard CIS Questionnaire contains 20 questions, each scoring 1 to 7, total score 20 - 140, with higher score indicating more tiredness. Thus, a negative value in changing score (such as Day 5 - Day 1 baseline) means reduction of tiredness and verse versa.</description>
          <population>ITT</population>
          <units>Score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 3 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.78" spread="13.45"/>
                    <measurement group_id="O2" value="-4.28" spread="5.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.33" spread="12.99"/>
                    <measurement group_id="O2" value="-2.56" spread="5.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8 over Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.78" spread="16.27"/>
                    <measurement group_id="O2" value="-1.67" spread="7.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>A comparison between before and after RiaGev supplementation.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.014</p_value>
            <p_value_desc>p &lt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-8.33</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>12.99</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value in RiaGev group at Day 5 over Day 1 is reported.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A comparison between before and after supplementation with Comparator.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.049</p_value>
            <p_value_desc>p &lt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-2.56</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>5.66</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>The p value in Comparator group at Day 5 over Day 1 is reported.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator</title>
        <description>The number of out-of-norm incidence (as indicator of safety) will be reported. Clinical chemistry parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, electrolytes (Na, K, Cl), fasting glucose. When a parameter is within normal limit, it will been reported as 0 out-of-norm.</description>
        <time_frame>7 days</time_frame>
        <population>ITT Populaiton</population>
        <group_list>
          <group group_id="O1">
            <title>RiaGev</title>
            <description>RiaGev, 2000mg, BID&#xD;
RiaGev: Dietary supplementation</description>
          </group>
          <group group_id="O2">
            <title>Comparator</title>
            <description>Comparator matched to RiaGev, BID&#xD;
Comparator: Dietary ingredient</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator</title>
          <description>The number of out-of-norm incidence (as indicator of safety) will be reported. Clinical chemistry parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, electrolytes (Na, K, Cl), fasting glucose. When a parameter is within normal limit, it will been reported as 0 out-of-norm.</description>
          <population>ITT Populaiton</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Creatine Clearance</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fasting Blood Glucose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aspartate Transaminase (AST)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine Transaminase (ALT)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chloride</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemoglobin A1c</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Estimated Average Glucose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator.</title>
        <description>The number of out-of-norm hematology parameter incidence (as indicator of safety) will be reported. Hematology parameters include white blood cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), red blood cell (RBC) count, hemoglobin, hematocrit, platelet count, RBC indices (mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW). When a parameter is within normal limits, it is reported as 0 out-of-norm.</description>
        <time_frame>7 days</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>RiaGev</title>
            <description>RiaGev, 2000mg, BID&#xD;
RiaGev: Dietary supplementation</description>
          </group>
          <group group_id="O2">
            <title>Comparator</title>
            <description>Comparator matched to RiaGev, BID&#xD;
Comparator: Dietary ingredients</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator.</title>
          <description>The number of out-of-norm hematology parameter incidence (as indicator of safety) will be reported. Hematology parameters include white blood cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), red blood cell (RBC) count, hemoglobin, hematocrit, platelet count, RBC indices (mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW). When a parameter is within normal limits, it is reported as 0 out-of-norm.</description>
          <population>ITT population</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>White Blood Cell Counts</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Red Blood Cell Counts</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemoglobin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemotocrit</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean Corpuscular Volume</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean Corpuscular Hemoglobin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean Corpuscular Hemoglobin Concentration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Red Blood Cell Distribution Width</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Meran Package Volume</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nucleated Red Blood Cells (NRBCA)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Instrument Absolute Neotrophil Count (IANC)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Immature Granulocytes (IGAB)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Neutrophil Counts</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Lymphocyte Count</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Monocyte Count</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Eosinophil Counts</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute Basophil Count</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>The Number of Out-of-norm Vital Signs When Supplemented With RiaGev or Comparator</title>
        <description>Vital signs include blood pressure (BP) and heart rate (HR). The number of out-of-norm incidence will be reported. When a parameter is within normal limits, it is reported as 0 out-of-norm.</description>
        <time_frame>7 days</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>RiaGev</title>
            <description>RiaGev, 2000mg, BID&#xD;
RiaGev: Dietary supplementation</description>
          </group>
          <group group_id="O2">
            <title>Comparator</title>
            <description>Comparator matched to RiaGev, BID&#xD;
Comparator: Dietary ingredient</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Out-of-norm Vital Signs When Supplemented With RiaGev or Comparator</title>
          <description>Vital signs include blood pressure (BP) and heart rate (HR). The number of out-of-norm incidence will be reported. When a parameter is within normal limits, it is reported as 0 out-of-norm.</description>
          <population>ITT population</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Systolic Pressure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diastolic Pressure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>22 days</time_frame>
      <desc>Total number of post-emergent adverse events that are possibly relevant to the study.</desc>
      <group_list>
        <group group_id="E1">
          <title>RiaGev</title>
          <description>RiaGev, 2000mg, BID&#xD;
RiaGev: Dietary supplementation</description>
        </group>
        <group group_id="E2">
          <title>Comparator</title>
          <description>Comparator matched to RiaGev, BID&#xD;
Comparator: Dietary ingredient</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <description>Weakness, Resolved.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <description>Anorexia, Resolved.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <description>Joint Pain, Resolved</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Alex Xue, Chief Technology Officer</name_or_title>
      <organization>Bioenergy Life Science, Inc.</organization>
      <phone>763-746-0032 ext 3924</phone>
      <email>alex.xue@bioenergyls.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04483011
org study id: 19RNHB(1918)
nct id: NCT04483011
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This current randomized, double-blind, comparator-controlled, cross over study investigates
      the efficacy and safety of RiaGev™ via evaluation of NAD+, ATP, glucose, insulin,
      glutathione, and cortisol levels in healthy adults of ages 36-65.
Nicotinamide adenine dinucleotide (NAD+) is one of the essential cofactors required for the
      proper function of living cells, and depletion in NAD has been correlated to aging
      individuals as NAD is associated with oxidative stress and energy production. Per the
      Population Reference Bureau (PRB), it is estimated that by the year 2060, the number of
      Americans over the age of 65 will double to over 98 million. As well, over the years, there
      has been a continuous rise in obesity within older Americans, reaching 44% for women and 36%
      for men in the age range of 65-74. One of the most common chronic diseases that are
      accompanied by aging and obesity diabetes. In 2016 the WHO reported that approximately 1.6
      million deaths were attributed to diabetes. Half of these individuals had high blood glucose
      before the age of 70. Hence it is crucial to actively control blood glucose and oxidative
      stress during one's midlife stage.

      The investigating product RiaGev™ is the first and only commercially available product that
      contains Bioenergy Ribose® and vitamin B3. It increases NAD+ in the body efficiently to
      promote healthy mitochondria, active immunity, and cholesterol reduction. As a result,
      D-ribose is essential for healthy aging.

      Bioenergy Ribose® is a 5-carbon carbohydrate (C5H10O5) called D-ribose designated as a
      Generally Recognized as Safe (GRAS) substance by the US Food and Drug Administration (FDA).
      It is produced via the pentose phosphate pathway (PPP), which is fundamental for adenosine
      triphosphate (ATP) production. The PPP is a rate-limiting step that makes use of a short
      supply enzyme called glucose-6-phosphate dehydrogenase (G-6-PDH). Supplementation of D-ribose
      can bypass the PPP and directly contribute to ATP production. In addition, to its function
      for ATP production D-ribose is a critical element of deoxyribonucleic acid (DNA), ribonucleic
      acid (RNA), and acetyl coenzyme A. Provided there is a reduction in ATP production; aging is
      frequently due to a decline in mitochondria function. Hence, cell function and integrity are
      compromised, leading to chronic cardiovascular conditions and fatigue (6). With active
      D-ribose supplementation, improvements have been noted in several pathological conditions
      such as chronic fatigue syndrome, fibromyalgia, and myocardial dysfunction. Furthermore,
      D-ribose demonstrated improvements in athletic performances by recovering ATP levels and
      repairing cellular damage.

      Vitamin B3 is an essential water-soluble vitamin known as either niacin, nicotinic acid, or
      nicotinamide. It is found in foods such as chicken, beef, fish, nuts, legumes, and grains.
      Also, vitamin B3 can be obtained from conversions of tryptophan in the body. Therefore, foods
      with tryptophan such as milk, eggs, meat, and fish are another great source of vitamin B3.
      Once vitamin B3 is consumed, it is converted into two different active forms called NAD+ or
      nicotinamide adenine dinucleotide phosphate (NADP). NAD+ and NADP are essential for various
      metabolic redox processes with oxidized or reduced substrates. Cellular functions like genome
      integrity, gene expression, and cellular communication are carried out by NAD+ required
      enzymes. These required enzymes are also crucial for the production of ATP via energy
      transfer from carbohydrates, fats, and proteins. NADP is involved in fewer reactions than
      NAD+ such as cholesterol and fatty acid synthesis along with antioxidation. Lack of NAD+ has
      been associated with a variety of aging-related conditions such as metabolic syndrome,
      cardiovascular health, and cancer.

      This current randomized, double-blind, comparator-controlled, cross over study will
      investigate the efficacy and safety of RiaGev™ via evaluation of NAD+, glucose, insulin,
      glutathione, and cortisol levels in healthy adults of ages 36-65.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: randomized, double-blind, comparator-controlled, cross-over
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-blind
measure: Whole Blood NAD+ Level Change Over Baseline After Supplementation
time frame: Day 1 to Day 8
description: Whole blood NAD+ concentration are measured at Day 1, Day 3, Day 5, and Day 8. A NAD+ Level change over baseline (Day 1) is calculated by subtracting the NAD+ level at Day 1 ( e.g Day 5 over Day 1 = Day 5 - Day 1). The significance of change (p value) is calculated comparing within RiaGev or Comparator group, and between RiaGev and Comparator groups.
measure: Whole Blood NADP+ Level Change Over Baseline After Supplementation
time frame: Day 1 to Day 8
description: Whole blood NADP+ concentration are measured at Day 1, Day 3, Day 5, and Day 8. NADP+ level changes over baseline (Day 1) are calculated by substracting NADP+ level at Day 1. The significance of change (p values) are calculated comparing changes within and between RiaGev and Comparator groups.
measure: Whole Blood NAD+ Plus NADP+ Level Change Over Baseline
time frame: Day 1 to 8
description: The change in whole blood NAD+ plus NADP+ levels from Day 1 baseline to Day 8 when supplemented with RiaGev™ or comparator. The parameter is measured at Day 1, Day 3, Day 5, and Day 8. A change over baseline is calculated by subtracting Day 1 value. The significance of changes (p value) are calculated by comparing within and between RiaGev and Comparator groups.
measure: Serum Glucose Change After RiaGev Supplementation Assessed by OGTT
time frame: 7 days
description: The serum glucose as assessed by a standard Oral Glucose Tolerance Test (OGTT) on Day 1 and on Day 8 after 7-day supplementation with either RiaGev™ or comparator. Incremental Area Under the Curve (iAUC) is used as overall blood glucose. Serum glucose change is calculated by subtracting iAUC on Day 1 from iAUC on Day 8. The significance of change (p value) is calculated by comparing values on Day 8 and Day 1.
measure: Serum Insulin Change After RiaGev Supplementation Assessed by OGTT
time frame: 7 days
description: Serum insulin is assessed by a standard Oral Glucose Tolerance Test (OGTT) on Day 1 and Day 8 after 7-day supplementation with either RiaGev™ or comparator. Serum insulin change is calculated by substracting its level on Day 1 from Day 8. The significance of change (p value) is calculated by comparing Day 1 and Day 8.
measure: Serum Glutathione (GSH + GSSG) Change Over Baseline After RiaGev Supplementation
time frame: 7 days
description: Total serum Glutathione (GSH + GSSG) is measured on Day 1, Day 3, Day 5 and Day 8. after a 7-day supplementation with either RiaGev™ or comparator. A change over baseline is calculated by subtracting glutathione level on Day 1 baseline (e g Day 5 over Day 1 = Day 5 - Day 1). The significance of change (p value) is calculated within the RiaGev or Comparator group.
measure: Serum High Energy Phosphate (ATP + ADP) Concentration After RiaGev Supplementation
time frame: 7 days
description: Serum high energy phosphate (ATP + ADP) after a 7-day supplementation with either RiaGev™ or comparator. The measurement take place on Day 1, Day 3, Day 5, and Day 8. Comparison are made between the two groups. The significance (p value) is also calculated between the groups.
measure: The Waking Salivary Cortisol Level After RiaGev Supplementation
time frame: 7 days
description: The salivary cortisol level after a 7-day supplementation with either RiaGev™ or comparator. The measurement take place on Day 1, 3, 5, and 8. The salivary cortisol level as well as change of salivary cortisol level over baseline (Day 1) are reported. Comparisons are make both between the RiaGev and Comparison groups as well as within RiaGev group against its Day 1 baseline. The corresponding significance (p value) will be calculated.
measure: The Change in Checklist Individual Strength (CIS) Questionnaire Outcome After a 7-day Supplementation With Either RiaGev™ or Comparator.
time frame: 7 days
description: Checklist Individual Strength (CIS) Questionnaire was designed by the Dutch research team of Vercoulen et el, to measure fatigues. A standard CIS Questionnaire contains 20 questions, each scoring 1 to 7, total score 20 - 140, with higher score indicating more tiredness. Thus, a negative value in changing score (such as Day 5 - Day 1 baseline) means reduction of tiredness and verse versa.
measure: The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator
time frame: 7 days
description: The number of out-of-norm incidence (as indicator of safety) will be reported. Clinical chemistry parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, electrolytes (Na, K, Cl), fasting glucose. When a parameter is within normal limit, it will been reported as 0 out-of-norm.
measure: The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator.
time frame: 7 days
description: The number of out-of-norm hematology parameter incidence (as indicator of safety) will be reported. Hematology parameters include white blood cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), red blood cell (RBC) count, hemoglobin, hematocrit, platelet count, RBC indices (mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW). When a parameter is within normal limits, it is reported as 0 out-of-norm.
measure: The Number of Out-of-norm Vital Signs When Supplemented With RiaGev or Comparator
time frame: 7 days
description: Vital signs include blood pressure (BP) and heart rate (HR). The number of out-of-norm incidence will be reported. When a parameter is within normal limits, it is reported as 0 out-of-norm.
arm group label: RiaGev
arm group type: Experimental
description: RiaGev, 2000mg, BID
arm group label: Comparator
arm group type: Active Comparator
description: Comparator matched to RiaGev, BID
intervention type: Dietary Supplement
intervention name: RiaGev
description: Dietary supplementation
arm group label: Comparator
arm group label: RiaGev
criteria: 
gender: All
minimum age: 36 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Malkanthi Evans, Ph.D
role: Study Chair
affiliation: KGK Science Inc.
last name: Trisha Shamp, PA-C, Ph.D
role: Principal Investigator
affiliation: Prism Research, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Metabolic Syndrome
mesh term: Aging, Premature
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 