Covid19Phase 4NCT04809974

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

A Phase 4 study testing Niagen in people with Covid19 and Sequelae of; Infection, run by Massachusetts General Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Covid19, Sequelae of; Infection, Cognitive Symptom
What is being tested?: Niagen
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 72 participants
Where: 1 siteUnited States
Study dates: 28 Aug 2021to 23 Feb 2024
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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;

Show all 11Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Clinical Translational Research Unit
Boston, Massachusetts, 02129

Other trials in United States

About this study

Official title: 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")

Read the 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.

Conditions: Covid19, Sequelae of; Infection, Cognitive Symptom
Being tested: Niagen
Keywords: Niagen, vitamin B3, Long-COVID, Long-haulers, Dietary supplement
Medical subject headings: COVID-19, Infections, Neurobehavioral Manifestations, Post-Acute COVID-19 Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NiagenDrug
Also called Nicotinamide Riboside, TruNiagen, Vitamin B3
The intervention consists of taking Niagen and completing all tasks divided into 6 visits.

Study groups in NCT04809974
Study group	Role	What they receive
Placebo	Placebo comparator	Placebo: 40 participants will take placebo in the form of a capsule. Receives: Drug: Niagen
Niagen	Experimental	Supplement: 60 participants will take Niagen 2000mg in the form of capsules daily. Receives: Drug: Niagen

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, Week 10 and Week 20

Secondary outcomes (3)

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.
Measured: 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.
Measured: 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.
Measured: Baseline, Week 10 and Week 20

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Aug 202123 Feb 2024

First posted22 Mar 2021
Study start28 Aug 2021
Primary completion5 Oct 2023
Study completion23 Feb 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Covid19Studies of the same condition, open and under way.
More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Double-blinded, randomized, parallel group, placebo-controlled design
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 72 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04809974
Sponsor's protocol ID: 2021P000158
Status last verified: Jul 2025
First submitted: 19 Mar 2021
Last updated: 5 Aug 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 41357333

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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")
ClinicalTrials.gov ID: NCT04809974
Acronym / sponsor ID: 2021P000158
Conditions: Covid19, Sequelae of; Infection, Cognitive Symptom
Keywords: Niagen, vitamin B3, Long-COVID, Long-haulers, Dietary supplement
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 72 participants (actual)
Lead sponsor: Massachusetts General HospitalUniversity, hospital or other
Study start: 28 Aug 2021 (actual)
Primary completion: 5 Oct 2023 (actual)
Study completion: 23 Feb 2024 (actual)
First posted: 22 Mar 2021 (actual)
Results: Posted 25 Jun 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Double-blinded, randomized, parallel group, placebo-controlled design

Arm	Type	Receives
Placebo	Placebo comparator	Drug: NiagenPlacebo: 40 participants will take placebo in the form of a capsule.
Niagen	Experimental	Drug: NiagenSupplement: 60 participants will take Niagen 2000mg in the form of capsules daily.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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;

Key exclusion criteria (11 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NiagenAlso: Nicotinamide Riboside, TruNiagen, Vitamin B3The intervention consists of taking Niagen and completing all tasks divided into 6 visits.	Drug	Niagen, Placebo

Primary outcome

Effect of Niagen on NAD+ and Cognitive Functioning
Time frame: Baseline, Week 10 and Week 20
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.

3 secondary outcomes

Effect of Niagen on NAD+ and Depression Symptoms
Time frame: Baseline, Week 10 and Week 20
Effect of Niagen on NAD+ and Anxiety Symptoms
Time frame: Baseline, Week 10 and Week 20
Effect of Niagen on NAD+ and Other COVID-related Symptoms
Time frame: Baseline, Week 10 and Week 20

Results and safety

Results posted to the registry on 25 Jun 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lead-in Phase	72	58
Placebo	0	0
Niagen	0	0

Primary outcome: Effect of Niagen on NAD+ and Cognitive Functioning

Time frame: Baseline, Week 10 and Week 20. Mean (Standard Deviation). Unit: units on a scale

Measure	Niagen n = 29	Placebo n = 21
ECog Total (Baseline to Week 10)	-0.104 (0.370)	-0.214 (0.370)
ECog Total (Week 10 to Week 20)	-0.014 (0.548)	-0.147 (0.236)
ECog Memory (Baseline to Week 10)	-0.222 (0.422)	-0.285 (0.564)
ECog Memory (Week 10 to Week 20)	0.068 (0.515)	-0.139 (0.498)
ECog Language (Baseline to Week 10)	-0.216 (0.415)	-0.289 (0.378)
ECog Language (Week 10 to Week 20)	0.068 (0.528)	-0.088 (0.321)
ECog Visualspatial (Baseline to Week 10)	0.103 (0.564)	-0.203 (0.460)
ECog Visualspatial (Week 10 to Week 20)	-0.132 (0.878)	-0.028 (0.283)

Population analysed: Only participants with complete outcome data at both timepoints relevant to a given change score were included in the analysis. Participants with missing data at either timepoint were excluded from the analysis for that specific outcome. As a result, the number of participants analyzed is lower than the total number randomized in each group.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were systematically collected at every visit, for a total of 24 weeks.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lead in	0 of 72 (0%)	1 of 72 (1.4%)	0 of 72
Placebo	0 of 21 (0%)	19 of 21 (90.5%)	0 of 21
Niagen	1 of 37 (2.7%)	25 of 37 (67.6%)	0 of 37

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 41357333Wu 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Edmarie Guzman-Velez, PhD principal investigator

Massachusetts General Hospital and Harvard Medical School

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Niagen in people with Covid19 and Sequelae of; Infection, run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect of Niagen on NAD+ and Cognitive Functioning (time frame: Baseline, Week 10 and Week 20). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04809974, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2025.