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

Randomized, Placebo-controlled Parallel Group Clinical Trial of Nicotinamide Riboside to Evaluate NAD+ Levels in Individuals With Persistent Cognitive and Physical Symptoms After COVID-19 Illness ("Long-COVID")

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.

Study Overview

• Status: Completed
• Conditions: Covid19; Cognitive Symptom; Sequelae of; Infection
• Intervention / Treatment: Drug: Niagen

Detailed Description

This study will recruit people who were infected with COVID-19 at least 2 months ago and continue to experience symptoms related to infection. Initially thought to be an acute illness like the flu, resulting in death for some or full recovery in most, scientists and clinicians are now appreciating that substantial numbers of COVID-19 illness survivors experience persistent, significant and sometimes disabling symptoms. Variously called "Long-COVID," "COVID long-haulers," or "chronic COVID syndrome", some of the most prominent symptoms are neurologic and neuropsychiatric, including cognitive impairment ('brain fog'), headache, fatigue, muscle aches and weakness, shortness of breath, hair loss and pain, among others. In this research study the investigators want to learn about whether taking Niagen (also known as Nicotinamide riboside, or NR), a daily supplement containing a form of Vitamin B3, can improve recovery of cognitive function, mood, and physical health in individuals who were infected with COVID-19 and continue to experience "brain fog" and other neurological and physical symptoms. The investigators think that this supplement may help improve thinking skills and other symptoms, and improve quality of life, in individuals who had COVID-19.

Participants will complete the following at baseline and every 5 weeks: 1) a standard cognitive battery and subjective cognitive complaints scales; 2) mood measures; 3) assessments of physical functioning, as well as of other common COVID-19-related symptoms; 4) blood draw; and 5) 2 optional MRIs. Participants will also wear a Fitbit and complete questionnaires to assess sleep and physical activity.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02129
      • Clinical Translational Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo: 40 participants will take placebo in the form of a capsule.	Drug: Niagen; The intervention consists of taking Niagen and completing all tasks divided into 6 visits.; Other Names: Vitamin B3; Nicotinamide Riboside; TruNiagen
Experimental: Niagen; Supplement: 60 participants will take Niagen 2000mg in the form of capsules daily.	Drug: Niagen; The intervention consists of taking Niagen and completing all tasks divided into 6 visits.; Other Names: Vitamin B3; Nicotinamide Riboside; TruNiagen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Niagen on NAD+ and Depression Symptoms	Depression symptoms were assessed using the Beck Depression Inventory (BDI), a 21-item self-report questionnaire measuring severity of depression symptoms. Total scores range from 0 to 63, with higher scores indicating more severe depression. Values represent mean change scores from Baseline to Week 10 and from Week 10 to Week 20.	Baseline, Week 10 and Week 20
Effect of Niagen on NAD+ and Anxiety Symptoms	Anxiety symptoms were assessed using the Beck Anxiety Inventory (BAI), a 21-item self-report questionnaire measuring severity of anxiety symptoms. Total scores range from 0 to 63, with higher scores indicating more severe anxiety. Values represent mean change scores from Baseline to Week 10 and from Week 10 to Week 20.	Baseline, Week 10 and Week 20
Effect of Niagen on NAD+ and Other COVID-related Symptoms	Fatigue was assessed using the Fatigue Severity Scale (FSS), a 9-item self-report measure with scores ranging from 1 to 7; higher scores indicate greater fatigue severity. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), a 19-item self-report measure with scores ranging from 0 to 21; higher scores indicate poorer sleep quality. All values represent mean change scores from Baseline to Week 10 and from Week 10 to Week 20.	Baseline, Week 10 and Week 20

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Edmarie Guzman-Velez, PhD, Massachusetts General Hospital and Harvard Medical School

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2021
• Primary Completion (Actual): October 5, 2023
• Study Completion (Actual): February 23, 2024

Study Registration Dates

• First Submitted: March 19, 2021
• First Submitted That Met QC Criteria: March 19, 2021
• First Posted (Actual): March 22, 2021

Study Record Updates

• Last Update Posted (Actual): August 5, 2025
• Last Update Submitted That Met QC Criteria: July 21, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Dietary supplement; Niagen; Long-COVID; vitamin B3; Long-haulers
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Neurobehavioral Manifestations; Physiological Effects of Drugs; Micronutrients; Vitamin B Complex; Vitamins; Niacinamide
• Other Study ID Numbers: 2021P000158

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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