<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/NCT04407390</url>
  </required_header>
  <id_info>
    <org_study_id>H-20026601</org_study_id>
    <nct_id>NCT04407390</nct_id>
  </id_info>
  <brief_title>Effects of Nicotinamide Riboside on the Clinical Outcome of Covid-19 in the Elderly</brief_title>
  <acronym>NR-COVID19</acronym>
  <official_title>Effects of Nicotinamide Riboside on the Clinical Outcome of Covid-19 in the Elderly. A Randomized Double-blind, Placebo-controlled Trial of Nicotinamide Riboside NR-COVID19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Copenhagen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bispebjerg Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Elysium Health</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Copenhagen</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 study is to investigate whether nicotinamide riboside supplementation can&#xD;
      attenuate the severity of SARS-CoV-2 infections in elderly patients.&#xD;
&#xD;
      A major event in aging is the loss of the central metabolite nicotinamide adenine&#xD;
      dinucleotide (NAD+) that appear to be important in the proinflammatory environment that occur&#xD;
      during aging. Notably, recent work from our and other groups suggest that aging can be&#xD;
      ameliorated by even a short-term treatment of the NAD+ precursor nicotinamide riboside.&#xD;
      Nicotinamide riboside has recently been shown to be able to return aging tissues to a younger&#xD;
      state even after short term treatment. This vitamin B3- analog is naturally occurring, is&#xD;
      readily taken up through oral administration and has been tested in human trials with few&#xD;
      side effects. In this randomized double blinded case-control trial, the investigators will&#xD;
      treat elderly (&gt;70 year old) COVID19 patients with 1 g of nicotinamide riboside (NR-E) or&#xD;
      placebo for 2 weeks and investigate if this affects the clinical course of the disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Currently the number of SARS-CoV-2 positive patients are increasing worldwide and healthcare&#xD;
      systems are attempting to cope with the massive pressure that this pandemic results in. Given&#xD;
      the highly infectious virus and the relatively high mortality, this pandemic will likely&#xD;
      result in many thousand casualties. Interventions are direly needed.&#xD;
&#xD;
      During the early reports of the pandemic it quickly became apparent that mortality was&#xD;
      primarily attributed to the elderly population. Indeed, the mortality rate of young adults&#xD;
      was around 0.2% while elderly Covid-19 patients displayed a mortality rate of ~20%. Thus,&#xD;
      fatality rates increase ~100 fold when comparing young adults to elderly individuals.&#xD;
&#xD;
      A major event in aging is the loss of the central metabolite nicotinamide adenine&#xD;
      dinucleotide (NAD+) that appear to be important in the proinflammatory environment that occur&#xD;
      during aging. Notably, recent work from our and other groups suggest that aging can be&#xD;
      ameliorated by even a short-term treatment of the NAD+ precursor nicotinamide riboside.&#xD;
      Nicotinamide riboside has recently been shown to be able to return aging tissues to a younger&#xD;
      state even after short term treatment. This vitamin B3- analog is naturally occurring, is&#xD;
      readily taken up through oral administration and has been tested in human trials with few&#xD;
      side effects. The purpose of this aim is to investigate if nicotinamide riboside can reduce&#xD;
      the severity of COVID-19 in patients aged 70 or older.&#xD;
&#xD;
      The elderly population is particularly problematic because long term respirator use for these&#xD;
      patients is connected with a substantial mortality risk. Interventions that can keep them&#xD;
      from fulminant respiratory failure is therefore of critical importance.&#xD;
&#xD;
      1.2 Study treatment: Nicotinamide riboside Nicotinamide riboside (NR-E, supplied by Elysium&#xD;
      Health) is a naturally occurring vitamin B3 analog produced by yeast and found in multiple&#xD;
      food products at low concentration. Many organisms including humans cannot produce&#xD;
      nicotinamide riboside but have evolved methods to convert this into the central redox&#xD;
      modulator NAD+.&#xD;
&#xD;
      The efficacy and safety of nicotinamide riboside has been tested in a number of studies in&#xD;
      both healthy controls and in patients suffering from metabolic disease, a risk factor for an&#xD;
      adverse outcome of COVID-19 patients. Since this is a natural compound widely found in nature&#xD;
      no subjects have yet developed allergic responses to the molecule, and repeated doses of up&#xD;
      to 2 g orally per day have demonstrated an acceptable safety profile.&#xD;
&#xD;
      No treatment-emergent adverse events have so far been reported for nicotinamide riboside&#xD;
&#xD;
      1.3 Rationale NAD+ is emerging as a central metabolic molecule involved in multiple&#xD;
      age-related pathways including inflammation and metabolic control. Notably, 2 weeks&#xD;
      nicotinamide riboside treatment increases metabolic output, normalizes muscle function and&#xD;
      reverses hypoxic responses in old mice. Recently, NAD+ has been shown to positively activate&#xD;
      the inflammatory response in various tissue and may be involved in polarizing macrophages&#xD;
      towards the M1 lineage and facilitate resolution of inflammation. Previously it was shown&#xD;
      that SARS-CoV-1 evades activation of the immune response and exogenous activation of&#xD;
      macrophages leads to a better outcome of SARS-CoV-1 infection. Thus, activation of elderly&#xD;
      macrophages via NAD+ replenishment could be an efficacious strategy in COVID-19 patients. In&#xD;
      addition, NAD+ replenishment may facilitate overall greater resilience of elderly patients&#xD;
      considering the anti-aging effects of nicotinamide riboside allowing these patients to better&#xD;
      cope with infections.&#xD;
&#xD;
      1.4 Rationale for study design and doses The purpose of this study is to investigate whether&#xD;
      nicotinamide riboside supplementation can attenuate the severity of SARS-CoV-2 infections.&#xD;
      The chosen dosage is 1 g per day given orally. This is lower than 2 g previously given to&#xD;
      healthy elderly individuals, however, this particular patient population have not been&#xD;
      treated with nicotinamide riboside previously so a slightly lower dose was chosen. In&#xD;
      addition, there is data suggesting that NAD+ regulates circadian rhythm and the dose is&#xD;
      therefore given in the morning.&#xD;
&#xD;
      The study design is as follows: Elderly patients (&gt;70 years old) seen with suspected COVID-19&#xD;
      at Bispebjerg hospital that are not requiring oxygen therapy are subjected to a COVID-19&#xD;
      test. The patients will be asked if they want to participate in this trial. If the patients&#xD;
      agree and if the COVID-19 test is positive the patients will be randomized to either placebo&#xD;
      or 1g nicotinamide riboside daily. Previous work has shown an efficacious increase in NAD+&#xD;
      levels combined with better physiological outcomes after 2 weeks treatment in preclinical&#xD;
      trials. The investigators will therefore treat patients for 2 weeks total with a primary&#xD;
      outcome of the study being hypoxic respiratory failure as defined by needing oxygen therapy.&#xD;
      The patients will be evaluated in the ambulatory at day 7 and after the treatment ends at day&#xD;
      14. Follow up in the ambulatory will occur three months after enrollment. If a patient is&#xD;
      admitted to the hospital during the treatment period the treatment continues for the full two&#xD;
      weeks. To evaluate outcomes, untargeted metabolomics and the NAD-ome will be measured in&#xD;
      peripheral blood mononucleated cells (PBMCs) upon enrolment, at day 7 and immediately after&#xD;
      the study as well as at follow up three months later. Changes in the epigenetic landscape is&#xD;
      a strong biomarker of age and is affected by NAD+ and epigenetic evaluation will be performed&#xD;
      in the PBMCs. Next generation machine learning data analysis will be applied to identify&#xD;
      predictors of clinical outcome.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No volunteers where recruited to this study. Other studies were prioritised over this at the&#xD;
    time of enrollment.&#xD;
  </why_stopped>
  <start_date type="Anticipated">June 1, 2020</start_date>
  <completion_date type="Anticipated">May 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2021</primary_completion_date>
  <phase>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>
    <intervention_model_description>Randomized double-blind case-control trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hypoxic respiratory failure</measure>
    <time_frame>Day 1</time_frame>
    <description>Hypoxic respiratory failure as defined by need for oxygen therapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hypoxic respiratory failure</measure>
    <time_frame>Day 7</time_frame>
    <description>Hypoxic respiratory failure as defined by need for oxygen therapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hypoxic respiratory failure</measure>
    <time_frame>Day 14</time_frame>
    <description>Hypoxic respiratory failure as defined by need for oxygen therapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hypoxic respiratory failure</measure>
    <time_frame>Day 90</time_frame>
    <description>Hypoxic respiratory failure as defined by need for oxygen therapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>Day 1</time_frame>
    <description>Overall mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>Day 7</time_frame>
    <description>Overall mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>Day 14</time_frame>
    <description>Overall mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>Day 90</time_frame>
    <description>Overall mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sepsis</measure>
    <time_frame>Day 1</time_frame>
    <description>Sepsis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sepsis</measure>
    <time_frame>Day 7</time_frame>
    <description>Sepsis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sepsis</measure>
    <time_frame>Day 14</time_frame>
    <description>Sepsis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sepsis</measure>
    <time_frame>Day 90</time_frame>
    <description>Sepsis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Circulatory failure</measure>
    <time_frame>Day 1</time_frame>
    <description>Circulatory failure as defined by a need for interventions to support the circulatory system.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Circulatory failure</measure>
    <time_frame>Day 7</time_frame>
    <description>Circulatory failure as defined by a need for interventions to support the circulatory system.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Circulatory failure</measure>
    <time_frame>Day 14</time_frame>
    <description>Circulatory failure as defined by a need for interventions to support the circulatory system.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Circulatory failure</measure>
    <time_frame>Day 90</time_frame>
    <description>Circulatory failure as defined by a need for interventions to support the circulatory system.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days in hospital</measure>
    <time_frame>Day 1</time_frame>
    <description>Days in hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days in hospital</measure>
    <time_frame>Day 7</time_frame>
    <description>Days in hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days in hospital</measure>
    <time_frame>Day 14</time_frame>
    <description>Days in hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days in hospital</measure>
    <time_frame>Day 90</time_frame>
    <description>Days in hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NAD levels</measure>
    <time_frame>Day 1</time_frame>
    <description>Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NAD levels</measure>
    <time_frame>Day 7</time_frame>
    <description>Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NAD levels</measure>
    <time_frame>Day 14</time_frame>
    <description>Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NAD levels</measure>
    <time_frame>Day 90</time_frame>
    <description>Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>COVID</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients receiving placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receiving nicotinamide riboside (NR-E)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Nicotinamide riboside</intervention_name>
    <description>The patients will receive 1 g of nicotinamide riboside or placebo orally every morning for 14 days.</description>
    <arm_group_label>NR</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent&#xD;
&#xD;
          2. Age 70 or older, inclusive at the time of diagnosis.&#xD;
&#xD;
          3. Body mass index between 18-40 kg/m2 (both inclusive) and weight ≥ 40 kg at enrolment.&#xD;
&#xD;
          4. A diagnosis of Covid-19.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Need for oxygen therapy.&#xD;
&#xD;
          2. Ongoing severe acute respiratory syndrome.&#xD;
&#xD;
          3. Cancer diagnosis within last 5 years.&#xD;
&#xD;
          4. Unwillingness or inability to follow the procedures outlined in the protocol.&#xD;
&#xD;
          5. Concurrent enrollment in another clinical study involving an investigational&#xD;
             treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>70 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Bispebjerg Hospital</name>
      <address>
        <city>Copenhagen NV</city>
        <zip>2400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>September 19, 2022</last_update_submitted>
  <last_update_submitted_qc>September 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Copenhagen</investigator_affiliation>
    <investigator_full_name>Morten Scheibye-Knudsen</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</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>


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/NCT04407390
org study id: H-20026601
nct id: NCT04407390
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to investigate whether nicotinamide riboside supplementation can
      attenuate the severity of SARS-CoV-2 infections in elderly patients.

      A major event in aging is the loss of the central metabolite nicotinamide adenine
      dinucleotide (NAD+) that appear to be important in the proinflammatory environment that occur
      during aging. Notably, recent work from our and other groups suggest that aging can be
      ameliorated by even a short-term treatment of the NAD+ precursor nicotinamide riboside.
      Nicotinamide riboside has recently been shown to be able to return aging tissues to a younger
      state even after short term treatment. This vitamin B3- analog is naturally occurring, is
      readily taken up through oral administration and has been tested in human trials with few
      side effects. In this randomized double blinded case-control trial, the investigators will
      treat elderly (>70 year old) COVID19 patients with 1 g of nicotinamide riboside (NR-E) or
      placebo for 2 weeks and investigate if this affects the clinical course of the disease.
Currently the number of SARS-CoV-2 positive patients are increasing worldwide and healthcare
      systems are attempting to cope with the massive pressure that this pandemic results in. Given
      the highly infectious virus and the relatively high mortality, this pandemic will likely
      result in many thousand casualties. Interventions are direly needed.

      During the early reports of the pandemic it quickly became apparent that mortality was
      primarily attributed to the elderly population. Indeed, the mortality rate of young adults
      was around 0.2% while elderly Covid-19 patients displayed a mortality rate of ~20%. Thus,
      fatality rates increase ~100 fold when comparing young adults to elderly individuals.

      A major event in aging is the loss of the central metabolite nicotinamide adenine
      dinucleotide (NAD+) that appear to be important in the proinflammatory environment that occur
      during aging. Notably, recent work from our and other groups suggest that aging can be
      ameliorated by even a short-term treatment of the NAD+ precursor nicotinamide riboside.
      Nicotinamide riboside has recently been shown to be able to return aging tissues to a younger
      state even after short term treatment. This vitamin B3- analog is naturally occurring, is
      readily taken up through oral administration and has been tested in human trials with few
      side effects. The purpose of this aim is to investigate if nicotinamide riboside can reduce
      the severity of COVID-19 in patients aged 70 or older.

      The elderly population is particularly problematic because long term respirator use for these
      patients is connected with a substantial mortality risk. Interventions that can keep them
      from fulminant respiratory failure is therefore of critical importance.

      1.2 Study treatment: Nicotinamide riboside Nicotinamide riboside (NR-E, supplied by Elysium
      Health) is a naturally occurring vitamin B3 analog produced by yeast and found in multiple
      food products at low concentration. Many organisms including humans cannot produce
      nicotinamide riboside but have evolved methods to convert this into the central redox
      modulator NAD+.

      The efficacy and safety of nicotinamide riboside has been tested in a number of studies in
      both healthy controls and in patients suffering from metabolic disease, a risk factor for an
      adverse outcome of COVID-19 patients. Since this is a natural compound widely found in nature
      no subjects have yet developed allergic responses to the molecule, and repeated doses of up
      to 2 g orally per day have demonstrated an acceptable safety profile.

      No treatment-emergent adverse events have so far been reported for nicotinamide riboside

      1.3 Rationale NAD+ is emerging as a central metabolic molecule involved in multiple
      age-related pathways including inflammation and metabolic control. Notably, 2 weeks
      nicotinamide riboside treatment increases metabolic output, normalizes muscle function and
      reverses hypoxic responses in old mice. Recently, NAD+ has been shown to positively activate
      the inflammatory response in various tissue and may be involved in polarizing macrophages
      towards the M1 lineage and facilitate resolution of inflammation. Previously it was shown
      that SARS-CoV-1 evades activation of the immune response and exogenous activation of
      macrophages leads to a better outcome of SARS-CoV-1 infection. Thus, activation of elderly
      macrophages via NAD+ replenishment could be an efficacious strategy in COVID-19 patients. In
      addition, NAD+ replenishment may facilitate overall greater resilience of elderly patients
      considering the anti-aging effects of nicotinamide riboside allowing these patients to better
      cope with infections.

      1.4 Rationale for study design and doses The purpose of this study is to investigate whether
      nicotinamide riboside supplementation can attenuate the severity of SARS-CoV-2 infections.
      The chosen dosage is 1 g per day given orally. This is lower than 2 g previously given to
      healthy elderly individuals, however, this particular patient population have not been
      treated with nicotinamide riboside previously so a slightly lower dose was chosen. In
      addition, there is data suggesting that NAD+ regulates circadian rhythm and the dose is
      therefore given in the morning.

      The study design is as follows: Elderly patients (>70 years old) seen with suspected COVID-19
      at Bispebjerg hospital that are not requiring oxygen therapy are subjected to a COVID-19
      test. The patients will be asked if they want to participate in this trial. If the patients
      agree and if the COVID-19 test is positive the patients will be randomized to either placebo
      or 1g nicotinamide riboside daily. Previous work has shown an efficacious increase in NAD+
      levels combined with better physiological outcomes after 2 weeks treatment in preclinical
      trials. The investigators will therefore treat patients for 2 weeks total with a primary
      outcome of the study being hypoxic respiratory failure as defined by needing oxygen therapy.
      The patients will be evaluated in the ambulatory at day 7 and after the treatment ends at day
      14. Follow up in the ambulatory will occur three months after enrollment. If a patient is
      admitted to the hospital during the treatment period the treatment continues for the full two
      weeks. To evaluate outcomes, untargeted metabolomics and the NAD-ome will be measured in
      peripheral blood mononucleated cells (PBMCs) upon enrolment, at day 7 and immediately after
      the study as well as at follow up three months later. Changes in the epigenetic landscape is
      a strong biomarker of age and is affected by NAD+ and epigenetic evaluation will be performed
      in the PBMCs. Next generation machine learning data analysis will be applied to identify
      predictors of clinical outcome.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized double-blind case-control trial
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Hypoxic respiratory failure
time frame: Day 1
description: Hypoxic respiratory failure as defined by need for oxygen therapy
measure: Hypoxic respiratory failure
time frame: Day 7
description: Hypoxic respiratory failure as defined by need for oxygen therapy
measure: Hypoxic respiratory failure
time frame: Day 14
description: Hypoxic respiratory failure as defined by need for oxygen therapy
measure: Hypoxic respiratory failure
time frame: Day 90
description: Hypoxic respiratory failure as defined by need for oxygen therapy
measure: Mortality
time frame: Day 1
description: Overall mortality
measure: Mortality
time frame: Day 7
description: Overall mortality
measure: Mortality
time frame: Day 14
description: Overall mortality
measure: Mortality
time frame: Day 90
description: Overall mortality
measure: Sepsis
time frame: Day 1
description: Sepsis
measure: Sepsis
time frame: Day 7
description: Sepsis
measure: Sepsis
time frame: Day 14
description: Sepsis
measure: Sepsis
time frame: Day 90
description: Sepsis
measure: Circulatory failure
time frame: Day 1
description: Circulatory failure as defined by a need for interventions to support the circulatory system.
measure: Circulatory failure
time frame: Day 7
description: Circulatory failure as defined by a need for interventions to support the circulatory system.
measure: Circulatory failure
time frame: Day 14
description: Circulatory failure as defined by a need for interventions to support the circulatory system.
measure: Circulatory failure
time frame: Day 90
description: Circulatory failure as defined by a need for interventions to support the circulatory system.
measure: Days in hospital
time frame: Day 1
description: Days in hospital
measure: Days in hospital
time frame: Day 7
description: Days in hospital
measure: Days in hospital
time frame: Day 14
description: Days in hospital
measure: Days in hospital
time frame: Day 90
description: Days in hospital
measure: NAD levels
time frame: Day 1
description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.
measure: NAD levels
time frame: Day 7
description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.
measure: NAD levels
time frame: Day 14
description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.
measure: NAD levels
time frame: Day 90
description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.
arm group label: Control
arm group type: Placebo Comparator
description: Patients receiving placebo.
arm group label: NR
arm group type: Experimental
description: Patients receiving nicotinamide riboside (NR-E)
intervention type: Dietary Supplement
intervention name: Nicotinamide riboside
description: The patients will receive 1 g of nicotinamide riboside or placebo orally every morning for 14 days.
arm group label: NR
intervention type: Dietary Supplement
intervention name: Placebo
description: Placebo
arm group label: Control
criteria: 
gender: All
minimum age: 70 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: University of Copenhagen
investigator full name: Morten Scheibye-Knudsen
investigator title: Associate Professor
mesh term: COVID-19
mesh term: Niacinamide
mesh term: Niacin
mesh term: Nicotinic Acids
sharing ipd: Undecided