Mental Intervention and Nicotinamide Riboside Supplementation in Long Covid

NCT05703074 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 983971636
• Study Type: interventional
• Target: 310
• Locations: 1 country
• Sites: 1

Brief Summary

Long COVID, also referred to as post-acute sequela of COVID-19 (PASC), is present in a substantial number of individuals, and treatment for this is warranted. Two different hypothetical models of Long COVID suggest attenuated mitochondrial energy production and functional brain alterations associated with psychosocial load, respectively, to be key mechanisms in the underlying pathophysiology. Given the potential importance of metabolic disturbances, dietary supplement by Nicotinamide Riboside (NR, sales name Niagen®) may be beneficial. Given the potential importance of functional brain alterations, a tailored and personalized Mind-Body Reprocessing Therapy (MBRT) may be beneficial. The MBRT consists of 4 to 6 face-to-face therapist encounters in combination with digital resources. The primary objective is to determine whether NR 1000 mg twice daily and/or MBRT increase health-related quality of life in individuals with Long COVID compared with care as usual and/or placebo. The Medical Outcome Study 36-item short form (SF-36), general health subscore is the primary endpoint. Secondary endpoints are: Markers of inflammation (hsCRP) and cognitive function (trail making test), cost-effectiveness, and the patient-reported symptoms fatigue, dyspnoea, and global impression of change in symptoms, function and quality of life. Explorative objectives encompass intervention effects on additional cognitive function markers, biological markers (indices of inflammation and autonomic nervous activity), disability markers (work attendance) and patient symptoms, as well as the exploration of long-term effects, differential subgroup effects, intervention effect mediators and intervention effect predictors. The study is a randomized controlled trial featuring a 2 x 2 factorial design where MBRT is compared with usual care and NR is compared with placebo. The latter comparison is double blinded. Eligible participants are individuals (18-70 years) with confirmed Long COVID interferring negatively with daily activities. A total of 310 participants will be enrolled. After baseline assessment (T1), the participants will be randomized 1:1 for both treatment comparisons, resulting in four treatment groups: a) MBRT and NR; b) usual care and NR; c) MBRT and placebo; d) usual care and placebo. All treatment periods last for three months, followed by primary endpoint assessment (T2). Total follow-up time is 12 months (T3). A comprehensive investigational program at all time points includes clinical examination, functional testing (spirometry, autonomic cardiovascular control, neurocognitive functions), sampling of biological specimens (blood) and questionnaire charting (background/demographics, clinical symptoms, psychosocial factors, study events).

Conditions

Long COVID

Outcome Measures

Primary Outcomes (1)

• Health-related quality of life

  The Medical Outcome Study 36-item short form (SF-36), general health subscore (total range 0 - 100, where higher scores indicate better QoL)

  Three months after inclusion (T2)

Secondary Outcomes (6)

• Inflammation

  Three months after inclusion (T2)

• Executive functioning

  Three months after inclusion (T2)

• Fatigue

  Three months after inclusion (T2)

• Dyspnoea

  Three months after inclusion (T2)

• Global impression of change

  Three months after inclusion (T2)

Other Outcomes (13)

• Subjective cognitive difficulties

  Three months after inclusion (T2)

• Worrying tendencies

  Three months after inclusion (T2)

• Sympathetic predominance

  Three months after inclusion (T2)

Study Arms (4)

MBRT and NR

OTHER

Psychological therapy and dietary supplement

Dietary Supplement: Nicotinamide Riboside (NR); Behavioral: Mind-body reprocessing therapy (MBRT)

MBRT and placebo

OTHER

Psychological therapy and placebo dietary supplement

Behavioral: Mind-body reprocessing therapy (MBRT); Dietary Supplement: Placebo

Care as usual and NR

OTHER

No psychological therapy (information only) and dietary supplement

Dietary Supplement: Nicotinamide Riboside (NR); Behavioral: Care as usual

Care as usual and placebo

OTHER

No psychological therapy (information only) and placebo dietary supplement

Behavioral: Care as usual; Dietary Supplement: Placebo

Interventions

Nicotinamide Riboside (NR) DIETARY_SUPPLEMENT

4 capsules (a total of 1000 mg) 2 times daily for 84 days

Care as usual and NR; MBRT and NR

Mind-body reprocessing therapy (MBRT) BEHAVIORAL

4-6 face-to-face meetings over 3-4 weeks, unlimited access to designated online resources.

MBRT and NR; MBRT and placebo

Care as usual BEHAVIORAL

A brief self-help leaflet on long COVID is distributed, otherwise care as usual by the general practitioner

Care as usual and NR; Care as usual and placebo

Placebo DIETARY_SUPPLEMENT

4 capsules (empty) 2 times daily for 84 days.

Care as usual and placebo; MBRT and placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Undergone acute COVID-19, confirmed EITHER by a positive PCR-test OR a positive self-test combined with confirmatory antibody-pattern in blood.
• Persistent symptoms at least 6 months following acute COVID-19 without symptom-free interval.
• Functional disability to an extent that impacts negatively on normal activities (such as work attendance, physical exercise, social activities, etc.)
• Informed consent

You may not qualify if:

• Other chronic illnesses, demanding life situations or concomitant drug use/substance abuse that is considered a plausible cause of persistent symptoms and associated disability
• Sustained organ damage (lung, heart, brain) following acute, serious Covid-19
• Pregnancy.
• Bedridden
• Insufficient command of Norwegian

Sponsors & Collaborators

• University Hospital, Akershus: lead

Study Sites (1)

Akershus University Hospital

Lørenskog, 1478, Norway

Location

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Torbjørn Omland, PhD

  Akershus University Hospital/University of Oslo

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: For the NR vs placebo comparison, participants, care providers, investigators and outcome assessors are blinded. For the MBRT vs. usual care comparison, due to the nature of the intervention, only outcome assessors are blinded
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: A 2 x 2 factorial randomized controlled trial, where Mind-Body Reprocessing Therapy (MBRT) is compared with care as usual and Nicotinamide Riboside (NR) is compared with placebo.

Study Record Dates

• First Submitted: January 25, 2023
• First Posted: January 27, 2023
• Study Start: January 30, 2023
• Primary Completion: September 23, 2024
• Study Completion: July 1, 2025
• Last Updated: February 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)