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
Trial Snapshot
- Phase
- Phase 2
- Status
- Withdrawn
- Sponsor
- University of Copenhagen
- Locations
- 1
- Primary Endpoint
- Hypoxic respiratory failure
Study Overview
Brief Summary
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.
Detailed Description
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+.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 70 Years to — (Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Written informed consent
- •Age 70 or older, inclusive at the time of diagnosis.
- •Body mass index between 18-40 kg/m2 (both inclusive) and weight ≥ 40 kg at enrolment.
- •A diagnosis of Covid-19.
Exclusion Criteria
- •Need for oxygen therapy.
- •Ongoing severe acute respiratory syndrome.
- •Cancer diagnosis within last 5 years.
- •Unwillingness or inability to follow the procedures outlined in the protocol.
- •Concurrent enrollment in another clinical study involving an investigational treatment.
Arms & Interventions
Control
Patients receiving placebo.
Intervention: Placebo (Dietary Supplement)
NR
Patients receiving nicotinamide riboside (NR-E)
Intervention: Nicotinamide riboside (Dietary Supplement)
Outcomes
Primary Outcomes
Hypoxic respiratory failure
Time Frame: Day 90
Hypoxic respiratory failure as defined by need for oxygen therapy
Hypoxic respiratory failure
Time Frame: Day 1
Hypoxic respiratory failure as defined by need for oxygen therapy
Hypoxic respiratory failure
Time Frame: Day 7
Hypoxic respiratory failure as defined by need for oxygen therapy
Hypoxic respiratory failure
Time Frame: Day 14
Hypoxic respiratory failure as defined by need for oxygen therapy
Secondary Outcomes
- NAD levels(Day 90)
- Mortality(Day 90)
- Sepsis(Day 90)
- Circulatory failure(Day 90)
- Days in hospital(Day 90)
- Mortality(Day 7)
- Mortality(Day 14)
- Sepsis(Day 1)
- Sepsis(Day 7)
- Sepsis(Day 14)
- Mortality(Day 1)
- Circulatory failure(Day 1)
- Circulatory failure(Day 7)
- Circulatory failure(Day 14)
- Days in hospital(Day 1)
- Days in hospital(Day 7)
- Days in hospital(Day 14)
- NAD levels(Day 1)
- NAD levels(Day 7)
- NAD levels(Day 14)
Investigators
Morten Scheibye-Knudsen
Associate Professor
University of Copenhagen