Mental Intervention and Nicotinamide Riboside Supplementation in Long Covid

Phase 2

Active, not recruiting

• Conditions: Long COVID
• Interventions: Behavioral: Care as usual; Behavioral: Mind-body reprocessing therapy (MBRT); Dietary Supplement: Nicotinamide Riboside (NR); Dietary Supplement: Placebo

• Registration Number: NCT05703074
• Lead Sponsor: University Hospital, Akershus

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-01-25
• Study First Submitted QC: 2023-01-25
• Study First Posted: 2023-01-27
• Study Start: 2023-01-30
• Primary Completion: 2024-09-23
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-03
• Last Update Posted: 2025-02-05
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 310

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Care as usual and placebo	Care as usual	No psychological therapy (information only) and placebo dietary supplement
MBRT and placebo	Mind-body reprocessing therapy (MBRT)	Psychological therapy and placebo dietary supplement
Care as usual and NR	Care as usual	No psychological therapy (information only) and dietary supplement
MBRT and NR	Mind-body reprocessing therapy (MBRT)	Psychological therapy and dietary supplement
Care as usual and NR	Nicotinamide Riboside (NR)	No psychological therapy (information only) and dietary supplement
MBRT and placebo	Placebo	Psychological therapy and placebo dietary supplement
MBRT and NR	Nicotinamide Riboside (NR)	Psychological therapy and dietary supplement
Care as usual and placebo	Placebo	No psychological therapy (information only) and placebo dietary supplement

Primary Outcome Measures

Name	Time	Method
Health-related quality of life	Three months after inclusion (T2)	The Medical Outcome Study 36-item short form (SF-36), general health subscore (total range 0 - 100, where higher scores indicate better QoL)

Secondary Outcome Measures

Name	Time	Method
Inflammation	Three months after inclusion (T2)	Plasma levels of C-reactive protein, high-sensitive assay (hsCRP). Higher levels indicate more inflammation
Executive functioning	Three months after inclusion (T2)	The Trail Making test, part B, seconds. Longer time indicates poorer executive functioning
Fatigue	Three months after inclusion (T2)	Chalder Fatigue Questionnaire (CFQ), total sum score (total range is from 0 - 33; higher scores indicate more fatigue)
Dyspnoea	Three months after inclusion (T2)	Medical Research Council dyspnoea scale. Total range is from 0 - 4, where higher scores indicate more dyspnoea
Global impression of change	Three months after inclusion (T2)	Patient Global Impression of Change (PGIC) inventory. Total range is from 1 - 7; higher scores imply that the health status is considered worsened
Cost-effectiveness	Three months after inclusion (T2)	Incremental cost-effectiveness ratio, using the 36-item short form (SF-36) general health subscore to determine quality-adjusted life years.

Trial Locations

Locations (1)

Akershus University Hospital; 🇳🇴 Lørenskog, Norway