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/NCT06032923</url>
    </required_header>
    <id_info>
      <org_study_id>10001621</org_study_id>
      <secondary_id>001621-H</secondary_id>
      <nct_id>NCT06032923</nct_id>
    </id_info>
    <brief_title>Pilot Study to Evaluate the Effect of NAD+ Boosting With Nicotinamide Riboside on Immunometabolism and Immunity in Systemic Lupus Erythematosus</brief_title>
    <official_title>Pilot Study to Evaluate the Effect of NAD+ Boosting With Nicotinamide Riboside on Immunometabolism and Immunity in Systemic Lupus Erythematosus</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
        <agency_class>NIH</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>National Institutes of Health Clinical Center (CC)</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Study Description:&#xD;
  &#xD;
        Systemic lupus erythematosus (SLE) occurs predominantly in women and is driven by type I&#xD;
        interferon dysregulation and neutrophil hyperresponsiveness. Neutrophils in females have&#xD;
        reduced mitochondrial bioenergetic capacity which affects immunometabolism. Nicotinamide&#xD;
        adenine dinucleotide (NAD)+ boosting with nicotinamide riboside blunts type 1 IFN activation&#xD;
        in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects. These findings support&#xD;
        the proposal of the hypothesis that NAD+ boosting by NR supplementation will modulate&#xD;
        metabolic pathways in lupus and blunt type 1 interferon signaling. Moreover, as type 1&#xD;
        interferon drives endothelial dysfunction, linked to increased cardiovascular risk, the&#xD;
        effect of NR on endothelial function will be examined.&#xD;
  &#xD;
        Objectives:&#xD;
  &#xD;
        Primary Objective: Evaluate the effect of NR vs. placebo on immunometabolic and inflammatory&#xD;
        remodeling in female SLE subjects:&#xD;
  &#xD;
        Exploratory Objective: Compare and characterize myeloid cell bioenergetic and immunometabolic&#xD;
        profiles in healthy control and SLE female subjects&#xD;
  &#xD;
        Endpoints:&#xD;
  &#xD;
        Primary Endpoint:&#xD;
  &#xD;
        The primary end point will be to assess the effect of NR on blunting type I IFN signaling by&#xD;
        measuring monocytic secretion of IFN-beta secretion compared to baseline in response to&#xD;
        placebo vs. NR supplemented in SLE study subjects.&#xD;
  &#xD;
        Exploratory Endpoints:&#xD;
  &#xD;
        Healthy control vs. SLE subjects:&#xD;
  &#xD;
          -  Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in&#xD;
             response to activation.&#xD;
  &#xD;
          -  Assess cell bioenergetics including: 1) monocyte and neutrophil metabolic flux mass&#xD;
             spectroscopy of 13C-glucose and 13Cglutamine analysis to investigate their metabolic&#xD;
             fates; (iii) Mitochondrial oxygen consumption (using glucose, amino acid, and fatty acid&#xD;
             substrates) and glycolysis rates.&#xD;
  &#xD;
        SLE baseline vs. NR/placebo supplementation:&#xD;
  &#xD;
        Baseline vs. 6 weeks of NR/placebo:&#xD;
  &#xD;
        -Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing&#xD;
        changes in placebo vs. NR groups in monocytes and neutrophils.&#xD;
  &#xD;
        Baseline vs. 12 weeks of NR/placebo:&#xD;
  &#xD;
          -  Whole blood NAD+ levels (batched and measured at the end of study enrollment period)&#xD;
  &#xD;
          -  Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and&#xD;
             chromatin remodeling analysis.&#xD;
  &#xD;
          -  Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Study Description:&#xD;
  &#xD;
        Systemic lupus erythematosus (SLE) occurs predominantly in women and is driven by type I&#xD;
        interferon dysregulation and neutrophil hyper-responsiveness. Neutrophils in females have&#xD;
        reduced mitochondrial bioenergetic capacity which affects immunometabolism. Nicotinamide&#xD;
        adenine dinucleotide (NAD)+ boosting with nicotinamide riboside blunts type 1 IFN activation&#xD;
        in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects. These findings support&#xD;
        the proposal of the hypothesis that NAD+ boosting by NR supplementation will modulate&#xD;
        metabolic pathways in lupus and blunt type 1 interferon signaling. Moreover, as type 1&#xD;
        interferon drives endothelial dysfunction, linked to increased cardiovascular risk, the&#xD;
        effect of NR on endothelial function will be examined.&#xD;
  &#xD;
        Objectives:&#xD;
  &#xD;
        Primary Objective: Evaluate the effect of NR vs. placebo on immunometabolic and inflammatory&#xD;
        remodeling in female SLE subjects:&#xD;
  &#xD;
        Exploratory Objective: Compare and characterize myeloid cell bioenergetic and immunometabolic&#xD;
        profiles in healthy control and SLE female subjects&#xD;
  &#xD;
        Endpoints:&#xD;
  &#xD;
        Primary Endpoint:&#xD;
  &#xD;
        The primary end point will be to assess the effect of NR on blunting type I IFN signaling by&#xD;
        measuring monocytic secretion of IFN-beta secretion compared to baseline in response to&#xD;
        placebo vs. NR supplemented in SLE study subjects.&#xD;
  &#xD;
        Exploratory Endpoints:&#xD;
  &#xD;
        Healthy control vs. SLE subjects:&#xD;
  &#xD;
          -  Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in&#xD;
             response to activation.&#xD;
  &#xD;
          -  Assess cell bioenergetics including: 1) monocyte and neutrophil metabolic flux mass&#xD;
             spectroscopy of 13C-glucose and 13C-glutamine analysis to investigate their metabolic&#xD;
             fates; (iii) Mitochondrial oxygen consumption (using glucose, amino acid, and fatty acid&#xD;
             substrates) and glycolysis rates.&#xD;
  &#xD;
        SLE baseline vs. NR/placebo supplementation:&#xD;
  &#xD;
        Baseline vs. 6 weeks of NR/placebo:&#xD;
  &#xD;
        -Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing&#xD;
        changes in placebo vs. NR groups in monocytes and neutrophils.&#xD;
  &#xD;
        Baseline vs. 12 weeks of NR/placebo:&#xD;
  &#xD;
          -  Whole blood NAD+ levels (batched and measured at the end of study enrollment period)&#xD;
  &#xD;
          -  Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and&#xD;
             chromatin remodeling analysis.&#xD;
  &#xD;
          -  Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 21, 2023</start_date>
    <completion_date type="Anticipated">August 1, 2028</completion_date>
    <primary_completion_date type="Anticipated">August 1, 2028</primary_completion_date>
    <phase>Phase 1/Phase 2</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>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>The primary end point will be to assess the effect of NR on blunting type I IFN signaling and cytokine secretion from placebo vs. NR supplemented subjects in monocytes comparing baseline (visit 1 to visit 3).</measure>
      <time_frame>4 years</time_frame>
      <description>Type 1 IFN dysregulation is present in SLE. NAD+ boosting blunts type 1 interferon in healthy subjects in-vivo and in monocytes of SLE subjects ex-vivo. Completion of data collection time is by 01/2027.</description>
    </primary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">78</enrollment>
    <condition>Systemic Lupus Erythematosus (Sle)</condition>
    <arm_group>
      <arm_group_label>Healthy controls</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>This group will not receive the dietary supplement or placebo.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Subjects with SLE - Active</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>This study group will take the dietary supplement Nicotinamide Riboside capsules.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Subjects with SLE - Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>This study group will take the Placebo.</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Nicotinamide Riboside</intervention_name>
      <description>The dietary supplement Nicotinamide Riboside or a placebo capsule in subjects with SLE. Niagen(R) is a commercially available form of nicotinamide riboside (NR)</description>
      <arm_group_label>Subjects with SLE - Active</arm_group_label>
      <arm_group_label>Subjects with SLE - Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          -  INCLUSION CRITERIA:&#xD;
  &#xD;
          In order to be eligible to participate in this study, an individual must meet all of the&#xD;
          following criteria:&#xD;
  &#xD;
          SLE subjects:&#xD;
  &#xD;
            -  Female subjects 18 years or older who meets &gt; 3 of 11 modified Am. Coll. of&#xD;
               Rheumatology (ACR) (1997) Revised Criteria for SLE and mild/moderate disease activity&#xD;
               defined as an SLE Disease Activity Index 2000(SLEDAI 2K) more than or equal to 2 and&#xD;
               less than or equal to 14 at screening;&#xD;
  &#xD;
            -  If on glucocorticoids, the dose must be less than or equal to 20 mg daily and stable&#xD;
               for at least 4 weeks prior to screening;&#xD;
  &#xD;
            -  If on hydroxychloroquine or other antimalarials such as chloroquine or quinacrine,&#xD;
               dose must have been stable for the 12 weeks prior to screening. The max. allowed doses&#xD;
               - hydroxychloroquine 400 mg/day, chloroquine phosphate 500 mg/day and quinacrine 100&#xD;
               mg/day;&#xD;
  &#xD;
            -  Subjects of childbearing potential must agree to practice effective birth control for&#xD;
               the duration of the study;&#xD;
  &#xD;
            -  Stated willingness to comply with all study procedures and availability for the&#xD;
               duration of the study;&#xD;
  &#xD;
            -  Agreement to adhere to Lifestyle Considerations throughout study duration;&#xD;
  &#xD;
            -  Ability of subject to understand and the willingness to sign a written informed&#xD;
               consent document.&#xD;
  &#xD;
          Control subjects:&#xD;
  &#xD;
            -  Female subjects 18 years or older&#xD;
  &#xD;
            -  No history of autoimmune or inflammatory disease;&#xD;
  &#xD;
          EXCLUSION CRITERIA:&#xD;
  &#xD;
          SLE Subjects:&#xD;
  &#xD;
            -  Active renal or central nervous system disease or major renal or hepatic dysfunction;&#xD;
  &#xD;
            -  Treatment with rituximab, belimumab or any other biologic agent within the 6 months&#xD;
               prior to screening&#xD;
  &#xD;
            -  Current treatment with specific immunosuppressive drugs (methotrexate, azathioprine,&#xD;
               mycophenolate mofetil, cyclosporine, tacrolimus);&#xD;
  &#xD;
            -  Treatment with cyclophosphamide or IVIG within the 6 months prior to screening and or&#xD;
               increase in glucocorticoid dose within 4 weeks of screening;&#xD;
  &#xD;
            -  Dietary vitamin B3 or tryptophan supplementation within 6 weeks of screening.&#xD;
  &#xD;
            -  Pregnancy or lactation (nursing)&#xD;
  &#xD;
            -  Treatment with another investigational drug or other intervention within 6 months of&#xD;
               screening&#xD;
  &#xD;
          Control Subjects:&#xD;
  &#xD;
            -  Inability to sign consent&#xD;
  &#xD;
            -  Dietary vitamin B3 or tryptophan supplementation within 6 weeks&#xD;
  &#xD;
            -  Pregnancy or nursing&#xD;
  &#xD;
          Pregnant women are excluded from participation on this study. Self-reported pregnancy&#xD;
          status may be accepted from female control participants of child-bearing potential for a&#xD;
          blood draw which is considered a minimal risk procedure.&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>120 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Michael N Sack, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>National Heart, Lung, and Blood Institute (NHLBI)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Rebecca D Huffstutler, C.R.N.P.</last_name>
      <phone>(301) 594-1281</phone>
      <email>rebecca.huffstutler@nih.gov</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Michael N Sack, M.D.</last_name>
      <phone>(301) 402-9259</phone>
      <email>ms761k@nih.gov</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>National Institutes of Health Clinical Center</name>
        <address>
          <city>Bethesda</city>
          <state>Maryland</state>
          <zip>20892</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>NIH Clinical Center Office of Patient Recruitment (OPR)</last_name>
        <phone>800-411-1222</phone>
        <phone_ext>TTY dial 711</phone_ext>
        <email>ccopr@nih.gov</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_001621-H.html</url>
      <description>NIH Clinical Center Detailed Web Page</description>
    </link>
    <verification_date>September 6, 2023</verification_date>
    <study_first_submitted>September 9, 2023</study_first_submitted>
    <study_first_submitted_qc>September 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 15, 2023</last_update_submitted>
    <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Lupus</keyword>
    <keyword>Chronic Inflammation</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lupus Erythematosus, Systemic</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Niacinamide</mesh_term>
      <mesh_term>Niacin</mesh_term>
      <mesh_term>Nicotinic Acids</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</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/NCT06032923
  org study id: 10001621
  secondary id: 001621-H
  nct id: NCT06032923
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Study Description:
  
        Systemic lupus erythematosus (SLE) occurs predominantly in women and is driven by type I
        interferon dysregulation and neutrophil hyperresponsiveness. Neutrophils in females have
        reduced mitochondrial bioenergetic capacity which affects immunometabolism. Nicotinamide
        adenine dinucleotide (NAD)+ boosting with nicotinamide riboside blunts type 1 IFN activation
        in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects. These findings support
        the proposal of the hypothesis that NAD+ boosting by NR supplementation will modulate
        metabolic pathways in lupus and blunt type 1 interferon signaling. Moreover, as type 1
        interferon drives endothelial dysfunction, linked to increased cardiovascular risk, the
        effect of NR on endothelial function will be examined.
  
        Objectives:
  
        Primary Objective: Evaluate the effect of NR vs. placebo on immunometabolic and inflammatory
        remodeling in female SLE subjects:
  
        Exploratory Objective: Compare and characterize myeloid cell bioenergetic and immunometabolic
        profiles in healthy control and SLE female subjects
  
        Endpoints:
  
        Primary Endpoint:
  
        The primary end point will be to assess the effect of NR on blunting type I IFN signaling by
        measuring monocytic secretion of IFN-beta secretion compared to baseline in response to
        placebo vs. NR supplemented in SLE study subjects.
  
        Exploratory Endpoints:
  
        Healthy control vs. SLE subjects:
  
          -  Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in
             response to activation.
  
          -  Assess cell bioenergetics including: 1) monocyte and neutrophil metabolic flux mass
             spectroscopy of 13C-glucose and 13Cglutamine analysis to investigate their metabolic
             fates; (iii) Mitochondrial oxygen consumption (using glucose, amino acid, and fatty acid
             substrates) and glycolysis rates.
  
        SLE baseline vs. NR/placebo supplementation:
  
        Baseline vs. 6 weeks of NR/placebo:
  
        -Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing
        changes in placebo vs. NR groups in monocytes and neutrophils.
  
        Baseline vs. 12 weeks of NR/placebo:
  
          -  Whole blood NAD+ levels (batched and measured at the end of study enrollment period)
  
          -  Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and
             chromatin remodeling analysis.
  
          -  Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects
  Study Description:
  
        Systemic lupus erythematosus (SLE) occurs predominantly in women and is driven by type I
        interferon dysregulation and neutrophil hyper-responsiveness. Neutrophils in females have
        reduced mitochondrial bioenergetic capacity which affects immunometabolism. Nicotinamide
        adenine dinucleotide (NAD)+ boosting with nicotinamide riboside blunts type 1 IFN activation
        in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects. These findings support
        the proposal of the hypothesis that NAD+ boosting by NR supplementation will modulate
        metabolic pathways in lupus and blunt type 1 interferon signaling. Moreover, as type 1
        interferon drives endothelial dysfunction, linked to increased cardiovascular risk, the
        effect of NR on endothelial function will be examined.
  
        Objectives:
  
        Primary Objective: Evaluate the effect of NR vs. placebo on immunometabolic and inflammatory
        remodeling in female SLE subjects:
  
        Exploratory Objective: Compare and characterize myeloid cell bioenergetic and immunometabolic
        profiles in healthy control and SLE female subjects
  
        Endpoints:
  
        Primary Endpoint:
  
        The primary end point will be to assess the effect of NR on blunting type I IFN signaling by
        measuring monocytic secretion of IFN-beta secretion compared to baseline in response to
        placebo vs. NR supplemented in SLE study subjects.
  
        Exploratory Endpoints:
  
        Healthy control vs. SLE subjects:
  
          -  Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in
             response to activation.
  
          -  Assess cell bioenergetics including: 1) monocyte and neutrophil metabolic flux mass
             spectroscopy of 13C-glucose and 13C-glutamine analysis to investigate their metabolic
             fates; (iii) Mitochondrial oxygen consumption (using glucose, amino acid, and fatty acid
             substrates) and glycolysis rates.
  
        SLE baseline vs. NR/placebo supplementation:
  
        Baseline vs. 6 weeks of NR/placebo:
  
        -Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing
        changes in placebo vs. NR groups in monocytes and neutrophils.
  
        Baseline vs. 12 weeks of NR/placebo:
  
          -  Whole blood NAD+ levels (batched and measured at the end of study enrollment period)
  
          -  Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and
             chromatin remodeling analysis.
  
          -  Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  measure: The primary end point will be to assess the effect of NR on blunting type I IFN signaling and cytokine secretion from placebo vs. NR supplemented subjects in monocytes comparing baseline (visit 1 to visit 3).
  time frame: 4 years
  description: Type 1 IFN dysregulation is present in SLE. NAD+ boosting blunts type 1 interferon in healthy subjects in-vivo and in monocytes of SLE subjects ex-vivo. Completion of data collection time is by 01/2027.
  arm group label: Healthy controls
  arm group type: No Intervention
  description: This group will not receive the dietary supplement or placebo.
  arm group label: Subjects with SLE - Active
  arm group type: Active Comparator
  description: This study group will take the dietary supplement Nicotinamide Riboside capsules.
  arm group label: Subjects with SLE - Placebo
  arm group type: Placebo Comparator
  description: This study group will take the Placebo.
  intervention type: Dietary Supplement
  intervention name: Nicotinamide Riboside
  description: The dietary supplement Nicotinamide Riboside or a placebo capsule in subjects with SLE. Niagen(R) is a commercially available form of nicotinamide riboside (NR)
  arm group label: Subjects with SLE - Active
  arm group label: Subjects with SLE - Placebo
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 120 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Michael N Sack, M.D.
  role: Principal Investigator
  affiliation: National Heart, Lung, and Blood Institute (NHLBI)
  last name: Rebecca D Huffstutler, C.R.N.P.
  phone: (301) 594-1281
  email: rebecca.huffstutler@nih.gov
  last name: Michael N Sack, M.D.
  phone: (301) 402-9259
  email: ms761k@nih.gov
  facility: 
  contact: 
  country: United States
  url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_001621-H.html
  description: NIH Clinical Center Detailed Web Page
  responsible party type: Sponsor
  mesh term: Lupus Erythematosus, Systemic
  mesh term: Niacinamide
  mesh term: Niacin
  mesh term: Nicotinic Acids
  sharing ipd: Undecided