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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury; SARS-CoV-2 Infection
• Intervention / Treatment: Drug: Placebo; Drug: Nicotinamide riboside

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029-6574
      • Icahn School of Medicine at Mount Sinai
  • Texas
    • San Antonio, Texas, United States, 78229
      • The University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229
      • University Health Systems
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form from a participant or legally authorized representative (LAR);
2. Male or female, >18 years old;
3. Hospitalized participants with a laboratory diagnosis of COVID-19 infection
4. Evidence of persistent AKI as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines (Table 3);
5. Willing to adhere to the study intervention regimen;

Exclusion Criteria:

1. Hypersensitivity to nicotinamide riboside (NR);
2. Pregnant or lactating women confirmed with positive laboratory pregnancy tests as per local requirements;
3. eGFR <15 mL/min/1.73 m2 as per the Chronic Kidney Disease Epidemiology Collaboration equation at admission lab;
4. Maintenance renal replacement therapy or initiation of renal replacement therapy before randomization
5. Currently on NR or nicotinamide or vitamin B3 (niacin) supplementation (multivitamins are allowed);
6. Concomitant cirrhosis of liver or acute liver failure;
7. 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;
8. Individuals with kidney transplant;
9. Individuals with blood platelet count <100,000/microL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Thrombocytopenia	Number occurrences of thrombocytopenia defined as >25% decline in blood platelet count from baseline.	Baseline to 10 days
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Proteinuria	Measurement of change in proteinuria at 30-90 days post randomization	30 days to 90 days
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

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Kumar Sharma, MD, UT Health San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2021
• Primary Completion (Actual): December 9, 2021
• Study Completion (Actual): January 3, 2022

Study Registration Dates

• First Submitted: March 24, 2021
• First Submitted That Met QC Criteria: March 24, 2021
• First Posted (Actual): March 26, 2021

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; COVID-19; Acute Kidney Injury; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: HSC20200914H; 3UH3DK114920-04S2 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected IPD, all IPD that underlie results in a publication
• IPD Sharing Time Frame: At the time when summary data are published or otherwise made available
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No