Clinical Trial of Niagen to Examine Recovery in People With Persistent Cognitive and Physical Symptoms After COVID-19

NCT04809974 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2021P000158
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The study will assess whether Niagen, a safe dietary supplement, improves recovery of COVID-19 related symptoms in individuals who were infected at least 2 months prior to study entry ("Long-COVID" "Long-haulers"). 60% of participants will receive Niagen and 40% will receive PBO. Outcomes will consist of standardized cognitive, neuropsychiatric, physical, functional and biomarker assessments.

Conditions

Covid19; Sequelae of; Infection; Cognitive Symptom

Keywords

Niagen; vitamin B3; Long-COVID; Long-haulers; Dietary supplement

Outcome Measures

Primary Outcomes (1)

• Effect of Niagen on NAD+ and Cognitive Functioning

  Cognitive outcomes were assessed using the Everyday Cognition (ECog) scale, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the Trail Making Test B (TMT-B). The ECog total score ranges from 39 to 156, and individual domain scores range from 1 to 4. Higher scores indicate greater subjective cognitive decline since COVID-19 infection. Individual RBANS index scores range from 40 to 160, and the Sum of Index Scores (sum of five index scores) ranges from 200 to 800. Higher index scores reflect better cognitive performance. The TMT-B score is the completion time in seconds, with a maximum time of 5 minutes. A lower time is indicative of a better performance. Change scores reflect the difference from Baseline to Week 10, and from Week 10 to Week 20. Positive change scores on the ECog indicate worsening subjective cognitive decline. Positive change scores on the RBANS indicate improvement. Positive change scores in the TMT-B represent worsening performance.

  Baseline, Week 10 and Week 20

Secondary Outcomes (3)

• Effect of Niagen on NAD+ and Depression Symptoms

  Baseline, Week 10 and Week 20

• Effect of Niagen on NAD+ and Anxiety Symptoms

  Baseline, Week 10 and Week 20

• Effect of Niagen on NAD+ and Other COVID-related Symptoms

  Baseline, Week 10 and Week 20

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo: 40 participants will take placebo in the form of a capsule.

Drug: Niagen

Niagen

EXPERIMENTAL

Supplement: 60 participants will take Niagen 2000mg in the form of capsules daily.

Drug: Niagen

Interventions

Niagen DRUG

The intervention consists of taking Niagen and completing all tasks divided into 6 visits.

Also known as: Nicotinamide Riboside, TruNiagen, Vitamin B3

Niagen; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of SARS-CoV-2 PCR+ at least 2 months prior to study entry;
• SARS-CoV-2 negative (PCR) at study entry;
• Persistent cognitive difficulties (esp. "brain fog") that began around the time of the acute COVID-19;
• At least two neurological and/or physical symptoms that started with COVID-19 infection and are ongoing at study entry, including fatigue, weakness, headache, loss of smell, tingling/numbness, shortness of breath, loss of appetite, palpitations/tachycardia, hair loss, musculoskeletal and/or chest pain;
• Willing and able to consent, complete all assessment and study procedures;
• Not pregnant or lactating.

You may not qualify if:

• Any specific central nervous system disease history (e.g. major clinical stroke, brain tumor, normal pressure hydrocephalus, etc);
• Clinically significant unstable medical condition that could affect safety or compliance with the study;
• Was intubated due to COVID-19;
• Major active or chronic unstable psychiatric illness (e.g. depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year;
• History of alcohol or other substance abuse or dependence within the past two years;
• Any significant systemic illness or medical condition that could affect safety or compliance with study;
• Current use of medications with psychoactive properties that may be deleteriously affecting cognition;
• Any known hypersensitivity to nicotinamide riboside, or its principal metabolite, nicotinamide mononucleotide;
• Use of other investigational agents or interventions one month prior to entry and for the duration of the trial;
• If participating in the optional magnetic resonance imaging (MRI) sub-study: Any contraindication to undergo MRI;
• Pregnant women or women who are planning to become pregnant within 7 months from study entry.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Clinical Translational Research Unit

Boston, Massachusetts, 02129, United States

Location

Related Publications (1)

• Wu CY, Reynolds WC, Abril I, McManus AJ, Brenner C, Gonzalez-Irizarry G, Gutierrez-Martinez L, Sun O, Rosand J, Tanzi RE, Arnold SE, Guzman-Velez E. Effects of nicotinamide riboside on NAD+ levels, cognition, and symptom recovery in long-COVID: a randomized controlled trial. EClinicalMedicine. 2025 Nov 12;89:103633. doi: 10.1016/j.eclinm.2025.103633. eCollection 2025 Nov.

  PMID: 41357333 DERIVED

MeSH Terms

Conditions

COVID-19; Infections; Neurobehavioral Manifestations; Post-Acute COVID-19 Syndrome

Interventions

nicotinamide-beta-riboside; Niacinamide

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

The sample size of individuals who completed the clinical trial was relatively small, and COVID-19 infection status was based on self-report. Moreover, we exclusively included individuals experiencing brain fog, preventing us from assessing whether NR could be beneficial for those with different long-COVID symptom profiles.

Results Point of Contact

• Title: Edmarie Guzmán-Vélez
• Organization: Massachusetts General Hospital

eguzman-velez@mgh.harvard.edu

6176436107

Study Officials

• Edmarie Guzman-Velez, PhD

  Massachusetts General Hospital and Harvard Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Double-blinded, randomized, parallel group, placebo-controlled design

Study Record Dates

• First Submitted: March 19, 2021
• First Posted: March 22, 2021
• Study Start: August 28, 2021
• Primary Completion: October 5, 2023
• Study Completion: February 23, 2024
• Last Updated: August 5, 2025
• Results First Posted: June 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)