xml: <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/NCT06005350</url>
    </required_header>
    <id_info>
      <org_study_id>NR-Charite</org_study_id>
      <nct_id>NCT06005350</nct_id>
    </id_info>
    <brief_title>Nicotinamide Riboside Impact on Extracellular Nicotinamide Adenine Dinucleotide (NAD+)</brief_title>
    <acronym>NICE</acronym>
    <official_title>Clinical Study to Validate an Enzymatic Assay for Quantification of Nicotinamide Adenine Dinucleotide in Blood Plasma After Ingestion of the Vitamin B3 Variant Nicotinamide Riboside.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Charite University, Berlin, Germany</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>ChromaDex, Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Charite University, Berlin, Germany</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The investigation is a clinical study in which the impact of taking the dietary supplement NR&#xD;
        on the concentration of eNAD+ in human plasma over time will be determined. The study will be&#xD;
        conducted in a randomized, double-blinded, and placebo-controlled manner.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The significance of NAD+ in promoting a healthy life is currently under intense research.&#xD;
        Despite an increasing number of research groups focusing on NAD+, there is no validated&#xD;
        measurement method for extracellular NAD+. With this research project, the investigators aim&#xD;
        to address this research gap.&#xD;
  &#xD;
        The coenzyme NAD+ is one of the central regulators of metabolism, existing mostly in its&#xD;
        oxidized form, NAD+, and its reduced form, NADH, in a dynamic equilibrium. NAD+ is&#xD;
        indispensable for various metabolic processes and plays a central role, especially in ATP&#xD;
        generation. It also enables gluconeogenesis, ketogenesis, pentose phosphate production, heme&#xD;
        and lipid synthesis, and the elimination of oxygen radicals.&#xD;
  &#xD;
        To validate the NAD+ Assay as a robust and reliable quantification method of extracellular&#xD;
        NAD+, a controlled increase of the measured metabolite in blood plasma is required through&#xD;
        NAD+ precursor administration.&#xD;
  &#xD;
        Multiple studies have already demonstrated that oral NR intake can increase NAD+ levels in&#xD;
        mammalian cells, rodent tissues, and peripheral blood mononuclear cells (PBMCs) in humans.&#xD;
        However, this relationship has not been explored in the extracellular space due to the lack&#xD;
        of reliable quantification of eNAD+ levels. Now, using the NAD+ Assay, the investigators aim&#xD;
        to examine the increase of eNAD+ after oral NR intake and provide initial data on the effects&#xD;
        of a 1000 mg/day dosage.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 4, 2023</start_date>
    <completion_date type="Anticipated">May 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">May 1, 2024</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>Basic Science</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>NR increases eNAD+</measure>
      <time_frame>10 days</time_frame>
      <description>The daily intake of 1,000 mg of NR changes the concentration of eNAD+ over the course of 10 days. The NAD+ Assay measures the changes of eNAD+ in plasma.</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">54</enrollment>
    <condition>NAD</condition>
    <arm_group>
      <arm_group_label>NR-Treatment</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>NR-Chlorid Preparation 1000mg/day for 10 days&#xD;
  (500mg - 0 - 500mg -0)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Placebo for 10 days&#xD;
  (1 - 0 - 1 - 0)</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Niagen</intervention_name>
      <description>Nicotinamide-Riboside-Chloride Preparation 1000mg/day</description>
      <arm_group_label>NR-Treatment</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Placebo Preperation</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Good general health&#xD;
  &#xD;
            -  Normal nutritional status and&#xD;
  &#xD;
            -  Age &gt;18 years.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnancy and/or lactation, or&#xD;
  &#xD;
            -  Severe psychiatric disorders, or&#xD;
  &#xD;
            -  Conditions that involve a general impairment of attentional performance, or&#xD;
  &#xD;
            -  Severe internal medical conditions, or&#xD;
  &#xD;
            -  Withdrawal of consent by the participant.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Can Kamali, MD</last_name>
      <phone>+49 30 450 552 001</phone>
      <email>can.kamali@charite.de</email>
    </overall_contact>
    <location>
      <facility>
        <name>Surgical Clinic, Campus Virchow-Klinikum / Campus Charité Mitte, Charité - Universitätsmedizin Berlin</name>
        <address>
          <city>Berlin</city>
          <zip>13353</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Germany</country>
    </location_countries>
    <reference>
      <citation>Bogan KL, Brenner C. Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu Rev Nutr. 2008;28:115-30. doi: 10.1146/annurev.nutr.28.061807.155443.</citation>
      <PMID>18429699</PMID>
    </reference>
    <reference>
      <citation>Brunnbauer P, Leder A, Kamali C, Kamali K, Keshi E, Splith K, Wabitsch S, Haber P, Atanasov G, Feldbrugge L, Sauer IM, Pratschke J, Schmelzle M, Krenzien F. The nanomolar sensing of nicotinamide adenine dinucleotide in human plasma using a cycling assay in albumin modified simulated body fluids. Sci Rep. 2018 Oct 31;8(1):16110. doi: 10.1038/s41598-018-34350-6.</citation>
      <PMID>30382125</PMID>
    </reference>
    <reference>
      <citation>Canto C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, Fernandez-Marcos PJ, Yamamoto H, Andreux PA, Cettour-Rose P, Gademann K, Rinsch C, Schoonjans K, Sauve AA, Auwerx J. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012 Jun 6;15(6):838-47. doi: 10.1016/j.cmet.2012.04.022.</citation>
      <PMID>22682224</PMID>
    </reference>
    <reference>
      <citation>Chi Y, Sauve AA. Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection. Curr Opin Clin Nutr Metab Care. 2013 Nov;16(6):657-61. doi: 10.1097/MCO.0b013e32836510c0.</citation>
      <PMID>24071780</PMID>
    </reference>
    <reference>
      <citation>Dolopikou CF, Kourtzidis IA, Margaritelis NV, Vrabas IS, Koidou I, Kyparos A, Theodorou AA, Paschalis V, Nikolaidis MG. Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study. Eur J Nutr. 2020 Mar;59(2):505-515. doi: 10.1007/s00394-019-01919-4. Epub 2019 Feb 6.</citation>
      <PMID>30725213</PMID>
    </reference>
    <reference>
      <citation>Imai SI, Guarente L. It takes two to tango: NAD+ and sirtuins in aging/longevity control. NPJ Aging Mech Dis. 2016 Aug 18;2:16017. doi: 10.1038/npjamd.2016.17. eCollection 2016.</citation>
      <PMID>28721271</PMID>
    </reference>
    <reference>
      <citation>Trammell SA, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, Li Z, Abel ED, Migaud ME, Brenner C. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016 Oct 10;7:12948. doi: 10.1038/ncomms12948.</citation>
      <PMID>27721479</PMID>
    </reference>
    <reference>
      <citation>Yoshino J, Baur JA, Imai SI. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018 Mar 6;27(3):513-528. doi: 10.1016/j.cmet.2017.11.002. Epub 2017 Dec 14.</citation>
      <PMID>29249689</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 9, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Charite University, Berlin, Germany</investigator_affiliation>
      <investigator_full_name>Felix Krenzien</investigator_full_name>
      <investigator_title>Principle Investigator</investigator_title>
    </responsible_party>
    <keyword>Nicotinamide riboside</keyword>
    <keyword>extracellular NAD+</keyword>
    <keyword>enzymatic assay</keyword>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06005350
  org study id: NR-Charite
  nct id: NCT06005350
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: Yes
  The investigation is a clinical study in which the impact of taking the dietary supplement NR
        on the concentration of eNAD+ in human plasma over time will be determined. The study will be
        conducted in a randomized, double-blinded, and placebo-controlled manner.
  The significance of NAD+ in promoting a healthy life is currently under intense research.
        Despite an increasing number of research groups focusing on NAD+, there is no validated
        measurement method for extracellular NAD+. With this research project, the investigators aim
        to address this research gap.
  
        The coenzyme NAD+ is one of the central regulators of metabolism, existing mostly in its
        oxidized form, NAD+, and its reduced form, NADH, in a dynamic equilibrium. NAD+ is
        indispensable for various metabolic processes and plays a central role, especially in ATP
        generation. It also enables gluconeogenesis, ketogenesis, pentose phosphate production, heme
        and lipid synthesis, and the elimination of oxygen radicals.
  
        To validate the NAD+ Assay as a robust and reliable quantification method of extracellular
        NAD+, a controlled increase of the measured metabolite in blood plasma is required through
        NAD+ precursor administration.
  
        Multiple studies have already demonstrated that oral NR intake can increase NAD+ levels in
        mammalian cells, rodent tissues, and peripheral blood mononuclear cells (PBMCs) in humans.
        However, this relationship has not been explored in the extracellular space due to the lack
        of reliable quantification of eNAD+ levels. Now, using the NAD+ Assay, the investigators aim
        to examine the increase of eNAD+ after oral NR intake and provide initial data on the effects
        of a 1000 mg/day dosage.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Basic Science
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: NR increases eNAD+
  time frame: 10 days
  description: The daily intake of 1,000 mg of NR changes the concentration of eNAD+ over the course of 10 days. The NAD+ Assay measures the changes of eNAD+ in plasma.
  arm group label: NR-Treatment
  arm group type: Experimental
  description: NR-Chlorid Preparation 1000mg/day for 10 days
  (500mg - 0 - 500mg -0)
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Placebo for 10 days
  (1 - 0 - 1 - 0)
  intervention type: Dietary Supplement
  intervention name: Niagen
  description: Nicotinamide-Riboside-Chloride Preparation 1000mg/day
  arm group label: NR-Treatment
  intervention type: Other
  intervention name: Placebo
  description: Placebo Preperation
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Can Kamali, MD
  phone: +49 30 450 552 001
  email: can.kamali@charite.de
  facility: 
  country: Germany
  citation: Bogan KL, Brenner C. Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu Rev Nutr. 2008;28:115-30. doi: 10.1146/annurev.nutr.28.061807.155443.
  PMID: 18429699
  citation: Brunnbauer P, Leder A, Kamali C, Kamali K, Keshi E, Splith K, Wabitsch S, Haber P, Atanasov G, Feldbrugge L, Sauer IM, Pratschke J, Schmelzle M, Krenzien F. The nanomolar sensing of nicotinamide adenine dinucleotide in human plasma using a cycling assay in albumin modified simulated body fluids. Sci Rep. 2018 Oct 31;8(1):16110. doi: 10.1038/s41598-018-34350-6.
  PMID: 30382125
  citation: Canto C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, Fernandez-Marcos PJ, Yamamoto H, Andreux PA, Cettour-Rose P, Gademann K, Rinsch C, Schoonjans K, Sauve AA, Auwerx J. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012 Jun 6;15(6):838-47. doi: 10.1016/j.cmet.2012.04.022.
  PMID: 22682224
  citation: Chi Y, Sauve AA. Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection. Curr Opin Clin Nutr Metab Care. 2013 Nov;16(6):657-61. doi: 10.1097/MCO.0b013e32836510c0.
  PMID: 24071780
  citation: Dolopikou CF, Kourtzidis IA, Margaritelis NV, Vrabas IS, Koidou I, Kyparos A, Theodorou AA, Paschalis V, Nikolaidis MG. Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study. Eur J Nutr. 2020 Mar;59(2):505-515. doi: 10.1007/s00394-019-01919-4. Epub 2019 Feb 6.
  PMID: 30725213
  citation: Imai SI, Guarente L. It takes two to tango: NAD+ and sirtuins in aging/longevity control. NPJ Aging Mech Dis. 2016 Aug 18;2:16017. doi: 10.1038/npjamd.2016.17. eCollection 2016.
  PMID: 28721271
  citation: Trammell SA, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, Li Z, Abel ED, Migaud ME, Brenner C. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016 Oct 10;7:12948. doi: 10.1038/ncomms12948.
  PMID: 27721479
  citation: Yoshino J, Baur JA, Imai SI. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018 Mar 6;27(3):513-528. doi: 10.1016/j.cmet.2017.11.002. Epub 2017 Dec 14.
  PMID: 29249689
  responsible party type: Principal Investigator
  investigator affiliation: Charite University, Berlin, Germany
  investigator full name: Felix Krenzien
  investigator title: Principle Investigator
  sharing ipd: No