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

Phase 4

Completed

• Conditions: Covid19; Sequelae of; Infection; Cognitive Symptom
• Interventions: Drug: Niagen

• Registration Number: NCT04809974
• Lead Sponsor: Massachusetts General Hospital

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.

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 Timeline

• Study First Submitted: 2021-03-19
• Study First Submitted QC: 2021-03-19
• Study First Posted: 2021-03-22
• Study Start: 2021-07-22
• Primary Completion: 2023-10-05
• Study Completion: 2024-02-23
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-18
• Last Update Posted: 2024-03-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Niagen	Placebo: 40 participants will take placebo in the form of a capsule.
Niagen	Niagen	Supplement: 60 participants will take Niagen 2000mg in the form of capsules daily.

Primary Outcome Measures

Name	Time	Method
Examine the effect of Niagen on cognitive functioning as measured by executive functioning and memory composite scores.	Baseline, 12 and 22 weeks	The investigators will examine the effect of Niagen on cognitive functioning through neuropsychological test scores that form executive functioning and memory composite scores.

Secondary Outcome Measures

Name	Time	Method
Examine the effect of Niagen in depression symptoms	Baseline and every 5 weeks for 22 weeks	Depression will be measured using the Beck Depression Inventory
Examine the effect of Niagen in COVID-related physical symptoms	Baseline and every 5 weeks for 22 weeks	COVID-related symptoms will be measured using a COVID symptom checklist that assesses number and severity of symptoms.
Examine the effect of Niagen in anxiety symptoms	Baseline and every 5 weeks for 22 weeks	Anxiety symptoms will be measured using the Beck Anxiety Inventory

Trial Locations

Locations (1)

Clinical Translational Research Unit; 🇺🇸 Boston, Massachusetts, United States