Nicotinamide Riboside in SARS-CoV-2 (COVID-19) Patients for Renal Protection

Study Overview
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Brief Summary
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An interventional clinical trial using oral nicotinamide riboside (NR) in hospitalized patients with COVID-19 infection and acute kidney injury to determine the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels and to evaluate safety of the use of NR.

Detailed Description
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The study team chose a treatment protocol with NR as a treatment for patients who will be admitted with COVID-19 related illness and develop AKI after admission. Treatment duration will be for 10 days and the primary study endpoint will be the change in whole blood NAD+ from baseline to end of treatment in NR group vs placebo group. The study team will evaluate whole blood NAD+ levels as a marker of efficacy and biological effect of NR.

Official Title
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NIRVANA: NIcotinamide Riboside in SARS-CoV-2 pAtients for reNAl Protection

Conditions
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SARS-CoV-2 Infection, Acute Kidney Injury

Intervention / Treatment
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* Drug: Placebo
* Drug: Nicotinamide riboside


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated informed consent form from a participant or legally authorized representative (LAR); Male or female, >18 years old; Hospitalized participants with a laboratory diagnosis of COVID-19 infection Evidence of persistent AKI as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines (Table 3); Willing to adhere to the study intervention regimen; Exclusion Criteria: Hypersensitivity to nicotinamide riboside (NR); Pregnant or lactating women confirmed with positive laboratory pregnancy tests as per local requirements; eGFR <15 mL/min/1.73 m2 as per the Chronic Kidney Disease Epidemiology Collaboration equation at admission lab; Maintenance renal replacement therapy or initiation of renal replacement therapy before randomization Currently on NR or nicotinamide or vitamin B3 (niacin) supplementation (multivitamins are allowed); Concomitant cirrhosis of liver or acute liver failure; Any medical history or condition that might, in the opinion of the attending physician, put the participant at significant risk if he/she were to participate in the trial; Individuals with kidney transplant; Individuals with blood platelet count <100,000/microL

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, double-blind, placebo-controlled clinical interventional trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Group<br>Placebo capsules will be administered 2 capsules twice daily for 10 days | Drug: Placebo<br>* Placebo capsule containing inert ingredient<br>* Other names: Microcrystalline cellulose;|
| Experimental: Nicotinamide Riboside Group<br>Nicotinamide riboside 250mg capsules will be administered 2 capsules twice daily for 10 days | Drug: Nicotinamide riboside<br>* 250 mg Nicotinamide riboside capsules<br>* Other names: Niagen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Whole Blood NAD+ Level | Measure of NAD+ level in whole blood from treatment beginning to end | Baseline to 10 days | 
| Number of Participants With Adverse Events of Grade 3 or Higher | Safety of NR in hospitalized patients with COVID-19 and AKI (defined as adverse event of Grade 3 or higher). Not every grade 3 event was considered to be serious. | Baseline to 10 days | 
| Occurrence of Thrombocytopenia | Number occurrences of thrombocytopenia defined as >25% decline in blood platelet count from baseline. | Baseline to 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Area Under the Curve (AUC) | To determine the effect of NR on changes in AUC serum creatinine from baseline during the 10-day intervention | Baseline to 10 days | 
| Effect of NR on Major Adverse Kidney Events (MAKE) | Number of occurrences of MAKE defined as doubling of serum creatinine, the initiation of long-term dialysis, or death from any cause. | 30 days to 90 days | 
| Change in Estimated Glomerular Filtration Rate (eGFR) | Measurement of change in eGFR at 30-90 days post randomization | 30 days to 90 days | 
| Change in Proteinuria | Measurement of change in proteinuria at 30-90 days post randomization | 30 days to 90 days |