<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/NCT03812211</url>
  </required_header>
  <id_info>
    <org_study_id>5754</org_study_id>
    <nct_id>NCT03812211</nct_id>
  </id_info>
  <brief_title>Evaluation of a Supplement for Weight Management in Obese and Overweight Individuals</brief_title>
  <official_title>Evaluation of a Supplement for Weight Management in Obese and Overweight Individuals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>McMaster University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>McMaster University</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>
      The purpose of this trial is to examine the effects of a novel, orally consumed dietary&#xD;
      supplement (composed of naturally occurring components) on weight management and metabolic&#xD;
      rate in individuals who are overweight or obese following a 12-week supplementation period.&#xD;
      The investigator's primary outcome will be changes in body composition measured via dual&#xD;
      energy x-ray absorptiometry (DXA), which will measure changes in fat and lean mass during the&#xD;
      supplementation period. Another primary objective will be to determine whether or not the&#xD;
      body mass index (BMI) changes during the supplementation period. A secondary objective of the&#xD;
      study is to determine whether anthropometric measurements (waist-to-hip ratio) is altered&#xD;
      following the supplementation period. Another secondary objective of this study is to&#xD;
      determine whether metabolic rate (as measured in VO2 consumption at rest and during exercise)&#xD;
      is changed following the supplementation period. Another secondary objective is to determine&#xD;
      whether blood pressure (systolic and diastolic pressure, measured in mm Hg) and physical&#xD;
      function (measured via VO2peak in mL/min/kg-1 and leg strength in kilograms) change when the&#xD;
      supplement is administered over a 12-week period. Another secondary objective will determine&#xD;
      how glycemic control, blood markers of inflammation and cholesterol are affected by this&#xD;
      intervention.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The present study is a randomized double-blind placebo controlled repeated measures design,&#xD;
      with sampling of the cohorts on five separate occasions.&#xD;
&#xD;
      Group 1: Intervention Group (n = 24) Healthy, overweight or obese physically inactive males,&#xD;
      supplement, n = 12 Healthy, overweight or obese physically inactive females, supplement, n=12&#xD;
      Group 2: Placebo Group (n = 24) Healthy, overweight or obese physically inactive males, no&#xD;
      supplement, n = 12 Healthy, overweight or obese physically inactive females, no supplement,&#xD;
      n=12&#xD;
&#xD;
      Participants will be asked to make 5 visits.&#xD;
&#xD;
      Day 0 (Visit 1): Eligible participants that provided informed consent will complete a medical&#xD;
      screening questionnaire to determine their readiness to perform exercise. Participants will&#xD;
      thus complete the SF-36 and CSEP Get Active Questionnaire form. Participant characteristics&#xD;
      will then be measured. At this time, anthropometric measurements (i.e., height, weight, waist&#xD;
      circumference) and a dual energy x-ray absorptiometry (DXA) measurement will be performed.&#xD;
      This must be done in order to verify that the participant meets the inclusion criteria of&#xD;
      being overweight. Following this screening, participants will begin the following the study&#xD;
      timeline.Upon completion, participants will be randomized into one of two groups.&#xD;
&#xD;
      Day 1 (Visit 2): Participants will arrive following an overnight fast (including no caffeine&#xD;
      for 12 hours) and having abstained from any exercise for the prior 48 hours. Participants&#xD;
      will enter the clinic, and rest quietly in the supine position for 25 minutes before having&#xD;
      blood pressure with a non-invasive automated cuff and resting metabolic rate via metabolic&#xD;
      cart measured. Following resting blood pressure and baseline metabolic rate assessment, blood&#xD;
      will be drawn from an antecubital vein. Thereafter, functional metrics will be determined&#xD;
      including strength (both upper and lower body muscles; and aerobic capacity (V02peak).&#xD;
      Following testing, participants will be provided with a 3-day diet log (which will be&#xD;
      completed every two weeks) and a pedometer.&#xD;
&#xD;
      Day 14 (Visit 3); Participants will arrive following an overnight fast (including no caffeine&#xD;
      for 12 hours) and having abstained from any exercise for the prior 24 hours. Participants&#xD;
      will undergo a DXA. Blood will be drawn from an antecubital vein.&#xD;
&#xD;
      Day 49 (Visit 4); Participants will arrive following an overnight fast (including no caffeine&#xD;
      for 12 hours) and having abstained from any exercise for the prior 24 hours. Participants&#xD;
      will undergo a DXA.&#xD;
&#xD;
      Follow-up - Day 7, 21, 28, 35, 42, 56, 63, 70, 77: Participants will receive a weekly phone&#xD;
      call to determine their pedometer counts for the week, and to ensure that participants are&#xD;
      adhering to the supplement consumption, and to address any concerns.&#xD;
&#xD;
      Day 84 (Visit 5); Participants will repeat Day 1 (automated blood pressure, resting and&#xD;
      maximal metabolic rate, blood draw, functional metrics. Participants will return their&#xD;
      pedometer and remuneration will be processed.&#xD;
&#xD;
      Study products (active supplement vs. placebo) will be provided in a blinded fashion by&#xD;
      Infinit Nutrition Canada (Windsor, Ontario). The active supplement is composed of vitamins,&#xD;
      minerals and naturally occurring and plant extracts approved for consumption. Participants&#xD;
      will be asked to consume 3 servings of the study product per day (7 days per week) throughout&#xD;
      the 12-wk intervention period. Participants will consume 1 serving immediately before&#xD;
      breakfast. Participants will be instructed to consume the supplement in a single sitting,&#xD;
      with water, within 5-10 min. Participants will be instructed to record product intake in a&#xD;
      diary to check compliance. Participants will also be asked to maintain the used package and&#xD;
      turn it in at the check-ins as a marker of study compliance. To maintain the double-blind&#xD;
      nature of the experiment, the placebo, which contains microcrystalline cellulose, will be&#xD;
      matched in size, appearance, taste and caloric value&#xD;
&#xD;
      Three day weighed food record. Participants will be asked to record everything that they&#xD;
      consumed for 3 non-consecutive days: 2 week-days and either a Saturday or a Sunday. On&#xD;
      completion of the food record, it will be analyzed using a commercially available&#xD;
      computerized database software (Nutribase version 11.5, Cybersoft Inc., Phoenix, AZ, USA).&#xD;
      Food items will be aggregated into the following categories: fruit (e.g., fresh/frozen,&#xD;
      tinned, juice), vegetables (e.g., fresh/frozen, canned), dairy products (e.g., milk, yoghurt,&#xD;
      cheese), breads and cereals (e.g., bread, breakfast cereal, rice, pasta), meats and&#xD;
      alternatives (e.g., red meat, poultry, fish, pork, processed meat, tofu, eggs, nuts) and&#xD;
      extra foods (e.g., hamburger, pizza, meat pies, chocolate, cake, ice cream, jam, biscuits,&#xD;
      crackers, crisps, alcohol etc.).&#xD;
&#xD;
      Resting metabolic rate (RMR). Participants will be asked to lay still on a bed will connected&#xD;
      to a metabolic cart with an on-line gas collection system (Moxus modular oxygen uptake&#xD;
      system, AEI Technologies, Pittsburgh, PA), and the system will acquire oxygen consumption&#xD;
      (VO2) and carbon dioxide (CO2) production data for 15 minutes.&#xD;
&#xD;
      Blood sampling. A total of ~16 mL blood per visit will be taken from the antecubital vein and&#xD;
      drawn into evacuated tubes with heparin used for plasma collection and non-treated tubes will&#xD;
      be used to collect serum. Blood sampling will be used for the following panel of tests:&#xD;
      complete blood count (CBC), glucose, Gamma-Glutamyl Transferase (GGT), bilirubin, Alanine&#xD;
      Aminotransferase (ALT), creatine kinase (CK), creatinine, triglycerides, total cholesterol,&#xD;
      LDL and HDL, insulin, CRP, and leptin.&#xD;
&#xD;
      Maximal voluntary VO2peak fitness test. Participants will complete double-leg incremental&#xD;
      peak oxygen uptake (VO2peak) tests on a cycle ergometer (Lode, Groningen, the Netherlands). A&#xD;
      metabolic cart with an on-line gas collection system (Moxus modular oxygen uptake system, AEI&#xD;
      Technologies, Pittsburgh, PA) will acquire oxygen consumption (VO2) and carbon dioxide (CO2)&#xD;
      production data. For double-leg cycling, the test will begin with a 1-min warm up at 50 watts&#xD;
      (W), after which the power will be increased by 1 W every two seconds until volitional&#xD;
      exhaustion or the point at which pedal cadence falls below 60 rpm. Heart rate will be&#xD;
      monitored continuously throughout the test via telemetry with a heart rate monitor (Polar A3,&#xD;
      Lake Success, NY). VO2peak will be defined as the highest oxygen consumption achieved over a&#xD;
      30-s period. Maximal workload (Wmax) will be the highest power output achieved during the&#xD;
      test. After the completion of the test, the participant will be asked to perform a 2-3-minute&#xD;
      active recovery pedaling against no resistance.&#xD;
&#xD;
      Pedometer. Participants will be given a wearable activity tracker (pedometer). All&#xD;
      participants will record their daily totals for subsequent analysis.&#xD;
&#xD;
      Dual X-ray absorptiometry (DXA) and blood pressure. A DXA scan is a non-invasive procedure&#xD;
      requiring the participant to only lay still on a padded table. It is a fast procedure that&#xD;
      provides a variety of body composition variables (bone mass/area/density, fat mass, and fat&#xD;
      free mass). The DXA scan exposes individuals to low levels of radiation, approximately 0.18&#xD;
      millirem. According to the United States Nuclear Regulatory Commission, Americans receive&#xD;
      approximately 620 millirem each year, half of which is due to environmental background&#xD;
      radiation. Radiation exposure can be due to medical treatments or procedures, like X-Ray or&#xD;
      MRI's, food, sun exposure, etc. Any exposure to radiation can increase the risk of cancer. In&#xD;
      the present study, body composition will be assessed using DXA scan (GE Lunar Prodigy,&#xD;
      Madison, WI) and a software program for adults (encore Version 9.15.010). Fat free mass&#xD;
      (FFM), fat mass (FM) and bone mineral density (BMD) of the entire body will be recorded.&#xD;
      Arterial blood pressure (i.e., systolic [SBP] and diastolic [DBP]) will be measured during&#xD;
      rest with a stethoscope (Marshall Nurse Stethoscope, Riverside, Ill., USA) and&#xD;
      sphygmomanometer (MDF Instruments Direct Inc., Agoura Hills, Calif., USA).&#xD;
&#xD;
      Waist and hip circumference measures. For waist circumference measurement, the participant&#xD;
      will stand with arms at the sides, feet together, and abdomen relaxed. Using a Gulick tape&#xD;
      measure, a horizontal measure will be taken at the narrowest part of the torso (above the&#xD;
      umbilicus and below the xiphoid process). Obtaining a horizontal measure directly above the&#xD;
      iliac crest enhances standardization according to The National Obesity Task Force. For hip&#xD;
      circumference measurement, the participant stands erect and feet together, a horizontal&#xD;
      measure is taken at the maximal circumference of buttocks.&#xD;
&#xD;
      Leg press 1RM. Assessment procedures for determining lower body strength using leg press&#xD;
      exercise equipment (Cybex Eagle ®, Medway, MA) will require the participant to sit in the leg&#xD;
      press machine with the right foot and left foot on the weight platform. The seat and back pad&#xD;
      will be adjusted so that feet are flat on the platform hip-width apart, toes slightly angled&#xD;
      out, and legs parallel to each other. The interviewer will then instruct the participant to&#xD;
      grasp the handles or sides of the seat and extend their legs leaving just a slight bend in&#xD;
      the knee. Next, the participant will remove the racking mechanism from the platform and grasp&#xD;
      the handles or seat again. The participant will begin with a selected weight that is within&#xD;
      their perceived ability, approximately 60 to 80% of maximum capacity (make an educated&#xD;
      guess). The participant will lower the platform slowly and controlled towards the chest,&#xD;
      keeping the hips and buttocks on the seat, and the back flat against the back pad. Once the&#xD;
      thighs are parallel to the platform the participant will extend the legs, pushing the weight&#xD;
      back to the start position as hard and as fast as possible. The participant will be&#xD;
      instructed to not allow their hips to shift to one side, the buttocks to rise, or knees to&#xD;
      move inward or outward during this exercise. The interviewer will also instruct the&#xD;
      participant to keep heels flat and not allow the knees to go beyond the toes. Once the&#xD;
      repetitions are completed, the participant will replace the racking mechanism and exit the&#xD;
      leg press. These procedures were adapted from procedures described by the National Strength&#xD;
      and Condition Association (2008) and the American College of Sports Medicine (2013).&#xD;
&#xD;
      Hand grip strength (MVIC; maximum voluntary isometric contraction). Hand grip strength will&#xD;
      be measured using an isometric dynamometer (JAMAR®, Sammons, Bolingbrook, IL). The grip width&#xD;
      will be adjusted to hand size and with arm flexed at 90°, the participant will perform three&#xD;
      X 5 s efforts with a one min rest between trials.&#xD;
&#xD;
      Knee extension (MVIC;maximum voluntary isometric contraction). Isometric knee extension will&#xD;
      be measured by mechanical dynamometry (Biodex System 3, Biodex Medical Systems, Shirley, NY).&#xD;
      Participants will be positioned into the machine with the knee flexed at 90° and perform&#xD;
      three X 5s maximal voluntary contractions with 30s rest between each trial.&#xD;
&#xD;
      Questionnaires. The RAND 36-Item Health Survey (Version 1.0) taps eight health concepts:&#xD;
      physical functioning, bodily pain, role limitations due to physical health problems, role&#xD;
      limitations due to personal or emotional problems, emotional well-being, social functioning,&#xD;
      energy/fatigue, and general health perceptions. It also includes a single item that provides&#xD;
      an indication of perceived change in health. The Get Active Questionnaire by CSEP is a&#xD;
      2-page, self-administered, pre-participation for exercise screening tool. Potential&#xD;
      participants must answer 'no' to all questions on the Get Active Questionnaire.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Anticipated">August 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">February 1, 2021</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Body composition</measure>
    <time_frame>12 weeks</time_frame>
    <description>Fat free mass and fat mass measured via DXA</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Body mass index</measure>
    <time_frame>12 weeks</time_frame>
    <description>Measure of body fat based on height and weight that applies to adult men and women</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>12 weeks</time_frame>
    <description>systolic and diastolic pressure, measured in mm Hg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle strength</measure>
    <time_frame>12 weeks</time_frame>
    <description>Leg strength measured via Biodex</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aerobic fitness</measure>
    <time_frame>12 weeks</time_frame>
    <description>VO2peak in mL/min/kg-1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fuel source utilization</measure>
    <time_frame>12 weeks</time_frame>
    <description>Consumed O2 compared to expired CO2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemaglobin A1C in mmol/mol</measure>
    <time_frame>12 weeks</time_frame>
    <description>Amount of glycated hemoglobin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of insulin in the blood</measure>
    <time_frame>12 weeks</time_frame>
    <description>Measures the amount of insulin in the blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of lipids in the blood</measure>
    <time_frame>12 weeks</time_frame>
    <description>Cholesterol, low density lipoprotein, high density lipoprotein, triglycerides in the blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life rating</measure>
    <time_frame>12 weeks</time_frame>
    <description>RAND SF(short form health survey)-36 Questionnaire; The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anthropometric measurements</measure>
    <time_frame>12 weeks</time_frame>
    <description>Waist-to-hip ratio measurements (in cm)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">48</enrollment>
  <condition>Overweight and Obesity</condition>
  <condition>Men</condition>
  <condition>Women</condition>
  <arm_group>
    <arm_group_label>Active Supplement</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will be allocated in a randomized, double-masked manner to receive a multi-faceted supplement for the 12-week duration of the study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be allocated in a randomized, double-masked manner to receive a placebo supplement (the placebo will be made of microcrystalline cellulose, and will be matched in size, appearance, taste and caloric value) for the 12-week duration of the study</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Active Supplement</intervention_name>
    <description>Examine the effects of a multi-faceted supplement comprised of vitamins, minerals and naturally occurring and plant extracts approved for consumption of in overweight/obese men and women</description>
    <arm_group_label>Active Supplement</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo supplement</intervention_name>
    <description>Examine the effects of a placebo supplement in overweight/obese men and women, compare to the active supplement</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female&#xD;
&#xD;
          -  overweight (BMI 25 - 29.9 kg/m2) or obese (BMI &gt; 30 kg/m2)&#xD;
&#xD;
          -  Physically inactive (&lt; 1 hour of formal exercise/week)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Participants will be excluded and/or released from the study if they meet any one of the&#xD;
        following:&#xD;
&#xD;
          -  Smoking&#xD;
&#xD;
          -  Use of assistive walking devices (e.g., cane, or walker)&#xD;
&#xD;
          -  Chronic use of analgesic or anti-inflammatory drugs&#xD;
&#xD;
          -  Diabetes mellitus (more than one anti-diabetic drug)&#xD;
&#xD;
          -  Cardiovascular disease (recent myocardial infarction (&lt; 6 months) and/or hypertension&#xD;
             requiring more than 2 medications)&#xD;
&#xD;
          -  Congestive heart failure requiring more than one medication for control&#xD;
&#xD;
          -  Renal disease (creatinine &gt; 140)&#xD;
&#xD;
          -  Previous stroke&#xD;
&#xD;
          -  Active musculoskeletal injuries and/or severe osteoarthritis&#xD;
&#xD;
          -  Significant weight loss in the 3-month period prior to the study&#xD;
&#xD;
          -  Vegan diet&#xD;
&#xD;
          -  Muscular dystrophy&#xD;
&#xD;
          -  Severe peripheral neuropathy&#xD;
&#xD;
          -  Severe osteoporosis&#xD;
&#xD;
          -  Use medications known to affect protein metabolism (i.e. corticosteroids)&#xD;
&#xD;
          -  Inability to consent&#xD;
&#xD;
          -  Chronic obstructive pulmonary disease, and asthma requiring more than two medications.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>McMaster University Medical Center</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8N 3Z5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Godard MP, Johnson BA, Richmond SR. Body composition and hormonal adaptations associated with forskolin consumption in overweight and obese men. Obes Res. 2005 Aug;13(8):1335-43. doi: 10.1038/oby.2005.162.</citation>
    <PMID>16129715</PMID>
  </reference>
  <reference>
    <citation>Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, Dimenna FJ, Wilkerson DP, Tarr J, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol (1985). 2009 Oct;107(4):1144-55. doi: 10.1152/japplphysiol.00722.2009. Epub 2009 Aug 6.</citation>
    <PMID>19661447</PMID>
  </reference>
  <reference>
    <citation>Cordero MD, Cano-Garcia FJ, Alcocer-Gomez E, De Miguel M, Sanchez-Alcazar JA. Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q(1)(0) effect on clinical improvement. PLoS One. 2012;7(4):e35677. doi: 10.1371/journal.pone.0035677. Epub 2012 Apr 19.</citation>
    <PMID>22532869</PMID>
  </reference>
  <reference>
    <citation>Maki KC, Reeves MS, Farmer M, Yasunaga K, Matsuo N, Katsuragi Y, Komikado M, Tokimitsu I, Wilder D, Jones F, Blumberg JB, Cartwright Y. Green tea catechin consumption enhances exercise-induced abdominal fat loss in overweight and obese adults. J Nutr. 2009 Feb;139(2):264-70. doi: 10.3945/jn.108.098293. Epub 2008 Dec 11.</citation>
    <PMID>19074207</PMID>
  </reference>
  <reference>
    <citation>Rasool AH, Yuen KH, Yusoff K, Wong AR, Rahman AR. Dose dependent elevation of plasma tocotrienol levels and its effect on arterial compliance, plasma total antioxidant status, and lipid profile in healthy humans supplemented with tocotrienol rich vitamin E. J Nutr Sci Vitaminol (Tokyo). 2006 Dec;52(6):473-8. doi: 10.3177/jnsv.52.473.</citation>
    <PMID>17330512</PMID>
  </reference>
  <reference>
    <citation>Thom E. The effect of chlorogenic acid enriched coffee on glucose absorption in healthy volunteers and its effect on body mass when used long-term in overweight and obese people. J Int Med Res. 2007 Nov-Dec;35(6):900-8. doi: 10.1177/147323000703500620.</citation>
    <PMID>18035001</PMID>
  </reference>
  <reference>
    <citation>Zembron-Lacny A, Slowinska-Lisowska M, Szygula Z, Witkowski K, Stefaniak T, Dziubek W. Assessment of the antioxidant effectiveness of alpha-lipoic acid in healthy men exposed to muscle-damaging exercise. J Physiol Pharmacol. 2009 Jun;60(2):139-43.</citation>
    <PMID>19617657</PMID>
  </reference>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>March 6, 2019</last_update_submitted>
  <last_update_submitted_qc>March 6, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>McMaster University</investigator_affiliation>
    <investigator_full_name>Mark Tarnopolsky</investigator_full_name>
    <investigator_title>Principal Investigator, Professor, Director of Neuromuscular and Neurometabolic Clinic</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Overweight</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03812211
org study id: 5754
nct id: NCT03812211
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this trial is to examine the effects of a novel, orally consumed dietary
      supplement (composed of naturally occurring components) on weight management and metabolic
      rate in individuals who are overweight or obese following a 12-week supplementation period.
      The investigator's primary outcome will be changes in body composition measured via dual
      energy x-ray absorptiometry (DXA), which will measure changes in fat and lean mass during the
      supplementation period. Another primary objective will be to determine whether or not the
      body mass index (BMI) changes during the supplementation period. A secondary objective of the
      study is to determine whether anthropometric measurements (waist-to-hip ratio) is altered
      following the supplementation period. Another secondary objective of this study is to
      determine whether metabolic rate (as measured in VO2 consumption at rest and during exercise)
      is changed following the supplementation period. Another secondary objective is to determine
      whether blood pressure (systolic and diastolic pressure, measured in mm Hg) and physical
      function (measured via VO2peak in mL/min/kg-1 and leg strength in kilograms) change when the
      supplement is administered over a 12-week period. Another secondary objective will determine
      how glycemic control, blood markers of inflammation and cholesterol are affected by this
      intervention.
The present study is a randomized double-blind placebo controlled repeated measures design,
      with sampling of the cohorts on five separate occasions.

      Group 1: Intervention Group (n = 24) Healthy, overweight or obese physically inactive males,
      supplement, n = 12 Healthy, overweight or obese physically inactive females, supplement, n=12
      Group 2: Placebo Group (n = 24) Healthy, overweight or obese physically inactive males, no
      supplement, n = 12 Healthy, overweight or obese physically inactive females, no supplement,
      n=12

      Participants will be asked to make 5 visits.

      Day 0 (Visit 1): Eligible participants that provided informed consent will complete a medical
      screening questionnaire to determine their readiness to perform exercise. Participants will
      thus complete the SF-36 and CSEP Get Active Questionnaire form. Participant characteristics
      will then be measured. At this time, anthropometric measurements (i.e., height, weight, waist
      circumference) and a dual energy x-ray absorptiometry (DXA) measurement will be performed.
      This must be done in order to verify that the participant meets the inclusion criteria of
      being overweight. Following this screening, participants will begin the following the study
      timeline.Upon completion, participants will be randomized into one of two groups.

      Day 1 (Visit 2): Participants will arrive following an overnight fast (including no caffeine
      for 12 hours) and having abstained from any exercise for the prior 48 hours. Participants
      will enter the clinic, and rest quietly in the supine position for 25 minutes before having
      blood pressure with a non-invasive automated cuff and resting metabolic rate via metabolic
      cart measured. Following resting blood pressure and baseline metabolic rate assessment, blood
      will be drawn from an antecubital vein. Thereafter, functional metrics will be determined
      including strength (both upper and lower body muscles; and aerobic capacity (V02peak).
      Following testing, participants will be provided with a 3-day diet log (which will be
      completed every two weeks) and a pedometer.

      Day 14 (Visit 3); Participants will arrive following an overnight fast (including no caffeine
      for 12 hours) and having abstained from any exercise for the prior 24 hours. Participants
      will undergo a DXA. Blood will be drawn from an antecubital vein.

      Day 49 (Visit 4); Participants will arrive following an overnight fast (including no caffeine
      for 12 hours) and having abstained from any exercise for the prior 24 hours. Participants
      will undergo a DXA.

      Follow-up - Day 7, 21, 28, 35, 42, 56, 63, 70, 77: Participants will receive a weekly phone
      call to determine their pedometer counts for the week, and to ensure that participants are
      adhering to the supplement consumption, and to address any concerns.

      Day 84 (Visit 5); Participants will repeat Day 1 (automated blood pressure, resting and
      maximal metabolic rate, blood draw, functional metrics. Participants will return their
      pedometer and remuneration will be processed.

      Study products (active supplement vs. placebo) will be provided in a blinded fashion by
      Infinit Nutrition Canada (Windsor, Ontario). The active supplement is composed of vitamins,
      minerals and naturally occurring and plant extracts approved for consumption. Participants
      will be asked to consume 3 servings of the study product per day (7 days per week) throughout
      the 12-wk intervention period. Participants will consume 1 serving immediately before
      breakfast. Participants will be instructed to consume the supplement in a single sitting,
      with water, within 5-10 min. Participants will be instructed to record product intake in a
      diary to check compliance. Participants will also be asked to maintain the used package and
      turn it in at the check-ins as a marker of study compliance. To maintain the double-blind
      nature of the experiment, the placebo, which contains microcrystalline cellulose, will be
      matched in size, appearance, taste and caloric value

      Three day weighed food record. Participants will be asked to record everything that they
      consumed for 3 non-consecutive days: 2 week-days and either a Saturday or a Sunday. On
      completion of the food record, it will be analyzed using a commercially available
      computerized database software (Nutribase version 11.5, Cybersoft Inc., Phoenix, AZ, USA).
      Food items will be aggregated into the following categories: fruit (e.g., fresh/frozen,
      tinned, juice), vegetables (e.g., fresh/frozen, canned), dairy products (e.g., milk, yoghurt,
      cheese), breads and cereals (e.g., bread, breakfast cereal, rice, pasta), meats and
      alternatives (e.g., red meat, poultry, fish, pork, processed meat, tofu, eggs, nuts) and
      extra foods (e.g., hamburger, pizza, meat pies, chocolate, cake, ice cream, jam, biscuits,
      crackers, crisps, alcohol etc.).

      Resting metabolic rate (RMR). Participants will be asked to lay still on a bed will connected
      to a metabolic cart with an on-line gas collection system (Moxus modular oxygen uptake
      system, AEI Technologies, Pittsburgh, PA), and the system will acquire oxygen consumption
      (VO2) and carbon dioxide (CO2) production data for 15 minutes.

      Blood sampling. A total of ~16 mL blood per visit will be taken from the antecubital vein and
      drawn into evacuated tubes with heparin used for plasma collection and non-treated tubes will
      be used to collect serum. Blood sampling will be used for the following panel of tests:
      complete blood count (CBC), glucose, Gamma-Glutamyl Transferase (GGT), bilirubin, Alanine
      Aminotransferase (ALT), creatine kinase (CK), creatinine, triglycerides, total cholesterol,
      LDL and HDL, insulin, CRP, and leptin.

      Maximal voluntary VO2peak fitness test. Participants will complete double-leg incremental
      peak oxygen uptake (VO2peak) tests on a cycle ergometer (Lode, Groningen, the Netherlands). A
      metabolic cart with an on-line gas collection system (Moxus modular oxygen uptake system, AEI
      Technologies, Pittsburgh, PA) will acquire oxygen consumption (VO2) and carbon dioxide (CO2)
      production data. For double-leg cycling, the test will begin with a 1-min warm up at 50 watts
      (W), after which the power will be increased by 1 W every two seconds until volitional
      exhaustion or the point at which pedal cadence falls below 60 rpm. Heart rate will be
      monitored continuously throughout the test via telemetry with a heart rate monitor (Polar A3,
      Lake Success, NY). VO2peak will be defined as the highest oxygen consumption achieved over a
      30-s period. Maximal workload (Wmax) will be the highest power output achieved during the
      test. After the completion of the test, the participant will be asked to perform a 2-3-minute
      active recovery pedaling against no resistance.

      Pedometer. Participants will be given a wearable activity tracker (pedometer). All
      participants will record their daily totals for subsequent analysis.

      Dual X-ray absorptiometry (DXA) and blood pressure. A DXA scan is a non-invasive procedure
      requiring the participant to only lay still on a padded table. It is a fast procedure that
      provides a variety of body composition variables (bone mass/area/density, fat mass, and fat
      free mass). The DXA scan exposes individuals to low levels of radiation, approximately 0.18
      millirem. According to the United States Nuclear Regulatory Commission, Americans receive
      approximately 620 millirem each year, half of which is due to environmental background
      radiation. Radiation exposure can be due to medical treatments or procedures, like X-Ray or
      MRI's, food, sun exposure, etc. Any exposure to radiation can increase the risk of cancer. In
      the present study, body composition will be assessed using DXA scan (GE Lunar Prodigy,
      Madison, WI) and a software program for adults (encore Version 9.15.010). Fat free mass
      (FFM), fat mass (FM) and bone mineral density (BMD) of the entire body will be recorded.
      Arterial blood pressure (i.e., systolic [SBP] and diastolic [DBP]) will be measured during
      rest with a stethoscope (Marshall Nurse Stethoscope, Riverside, Ill., USA) and
      sphygmomanometer (MDF Instruments Direct Inc., Agoura Hills, Calif., USA).

      Waist and hip circumference measures. For waist circumference measurement, the participant
      will stand with arms at the sides, feet together, and abdomen relaxed. Using a Gulick tape
      measure, a horizontal measure will be taken at the narrowest part of the torso (above the
      umbilicus and below the xiphoid process). Obtaining a horizontal measure directly above the
      iliac crest enhances standardization according to The National Obesity Task Force. For hip
      circumference measurement, the participant stands erect and feet together, a horizontal
      measure is taken at the maximal circumference of buttocks.

      Leg press 1RM. Assessment procedures for determining lower body strength using leg press
      exercise equipment (Cybex Eagle ®, Medway, MA) will require the participant to sit in the leg
      press machine with the right foot and left foot on the weight platform. The seat and back pad
      will be adjusted so that feet are flat on the platform hip-width apart, toes slightly angled
      out, and legs parallel to each other. The interviewer will then instruct the participant to
      grasp the handles or sides of the seat and extend their legs leaving just a slight bend in
      the knee. Next, the participant will remove the racking mechanism from the platform and grasp
      the handles or seat again. The participant will begin with a selected weight that is within
      their perceived ability, approximately 60 to 80% of maximum capacity (make an educated
      guess). The participant will lower the platform slowly and controlled towards the chest,
      keeping the hips and buttocks on the seat, and the back flat against the back pad. Once the
      thighs are parallel to the platform the participant will extend the legs, pushing the weight
      back to the start position as hard and as fast as possible. The participant will be
      instructed to not allow their hips to shift to one side, the buttocks to rise, or knees to
      move inward or outward during this exercise. The interviewer will also instruct the
      participant to keep heels flat and not allow the knees to go beyond the toes. Once the
      repetitions are completed, the participant will replace the racking mechanism and exit the
      leg press. These procedures were adapted from procedures described by the National Strength
      and Condition Association (2008) and the American College of Sports Medicine (2013).

      Hand grip strength (MVIC; maximum voluntary isometric contraction). Hand grip strength will
      be measured using an isometric dynamometer (JAMAR®, Sammons, Bolingbrook, IL). The grip width
      will be adjusted to hand size and with arm flexed at 90°, the participant will perform three
      X 5 s efforts with a one min rest between trials.

      Knee extension (MVIC;maximum voluntary isometric contraction). Isometric knee extension will
      be measured by mechanical dynamometry (Biodex System 3, Biodex Medical Systems, Shirley, NY).
      Participants will be positioned into the machine with the knee flexed at 90° and perform
      three X 5s maximal voluntary contractions with 30s rest between each trial.

      Questionnaires. The RAND 36-Item Health Survey (Version 1.0) taps eight health concepts:
      physical functioning, bodily pain, role limitations due to physical health problems, role
      limitations due to personal or emotional problems, emotional well-being, social functioning,
      energy/fatigue, and general health perceptions. It also includes a single item that provides
      an indication of perceived change in health. The Get Active Questionnaire by CSEP is a
      2-page, self-administered, pre-participation for exercise screening tool. Potential
      participants must answer 'no' to all questions on the Get Active Questionnaire.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Body composition
time frame: 12 weeks
description: Fat free mass and fat mass measured via DXA
measure: Body mass index
time frame: 12 weeks
description: Measure of body fat based on height and weight that applies to adult men and women
measure: Blood pressure
time frame: 12 weeks
description: systolic and diastolic pressure, measured in mm Hg
measure: Muscle strength
time frame: 12 weeks
description: Leg strength measured via Biodex
measure: Aerobic fitness
time frame: 12 weeks
description: VO2peak in mL/min/kg-1
measure: Fuel source utilization
time frame: 12 weeks
description: Consumed O2 compared to expired CO2
measure: Hemaglobin A1C in mmol/mol
time frame: 12 weeks
description: Amount of glycated hemoglobin
measure: Concentration of insulin in the blood
time frame: 12 weeks
description: Measures the amount of insulin in the blood.
measure: Concentration of lipids in the blood
time frame: 12 weeks
description: Cholesterol, low density lipoprotein, high density lipoprotein, triglycerides in the blood
measure: Quality of Life rating
time frame: 12 weeks
description: RAND SF(short form health survey)-36 Questionnaire; The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability
measure: Anthropometric measurements
time frame: 12 weeks
description: Waist-to-hip ratio measurements (in cm)
arm group label: Active Supplement
arm group type: Active Comparator
description: Participants will be allocated in a randomized, double-masked manner to receive a multi-faceted supplement for the 12-week duration of the study
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will be allocated in a randomized, double-masked manner to receive a placebo supplement (the placebo will be made of microcrystalline cellulose, and will be matched in size, appearance, taste and caloric value) for the 12-week duration of the study
intervention type: Dietary Supplement
intervention name: Active Supplement
description: Examine the effects of a multi-faceted supplement comprised of vitamins, minerals and naturally occurring and plant extracts approved for consumption of in overweight/obese men and women
arm group label: Active Supplement
intervention type: Dietary Supplement
intervention name: Placebo supplement
description: Examine the effects of a placebo supplement in overweight/obese men and women, compare to the active supplement
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Canada
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PMID: 16129715
citation: Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, Dimenna FJ, Wilkerson DP, Tarr J, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol (1985). 2009 Oct;107(4):1144-55. doi: 10.1152/japplphysiol.00722.2009. Epub 2009 Aug 6.
PMID: 19661447
citation: Cordero MD, Cano-Garcia FJ, Alcocer-Gomez E, De Miguel M, Sanchez-Alcazar JA. Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q(1)(0) effect on clinical improvement. PLoS One. 2012;7(4):e35677. doi: 10.1371/journal.pone.0035677. Epub 2012 Apr 19.
PMID: 22532869
citation: Maki KC, Reeves MS, Farmer M, Yasunaga K, Matsuo N, Katsuragi Y, Komikado M, Tokimitsu I, Wilder D, Jones F, Blumberg JB, Cartwright Y. Green tea catechin consumption enhances exercise-induced abdominal fat loss in overweight and obese adults. J Nutr. 2009 Feb;139(2):264-70. doi: 10.3945/jn.108.098293. Epub 2008 Dec 11.
PMID: 19074207
citation: Rasool AH, Yuen KH, Yusoff K, Wong AR, Rahman AR. Dose dependent elevation of plasma tocotrienol levels and its effect on arterial compliance, plasma total antioxidant status, and lipid profile in healthy humans supplemented with tocotrienol rich vitamin E. J Nutr Sci Vitaminol (Tokyo). 2006 Dec;52(6):473-8. doi: 10.3177/jnsv.52.473.
PMID: 17330512
citation: Thom E. The effect of chlorogenic acid enriched coffee on glucose absorption in healthy volunteers and its effect on body mass when used long-term in overweight and obese people. J Int Med Res. 2007 Nov-Dec;35(6):900-8. doi: 10.1177/147323000703500620.
PMID: 18035001
citation: Zembron-Lacny A, Slowinska-Lisowska M, Szygula Z, Witkowski K, Stefaniak T, Dziubek W. Assessment of the antioxidant effectiveness of alpha-lipoic acid in healthy men exposed to muscle-damaging exercise. J Physiol Pharmacol. 2009 Jun;60(2):139-43.
PMID: 19617657
responsible party type: Principal Investigator
investigator affiliation: McMaster University
investigator full name: Mark Tarnopolsky
investigator title: Principal Investigator, Professor, Director of Neuromuscular and Neurometabolic Clinic
mesh term: Overweight
sharing ipd: No