Mental Intervention and Nicotinamide Riboside Supplementation in Long Covid

Long COVID Clinical Trial

— MINIRICO  

Official title:

The Efficacy and Safety of a Mental Intervention Program vs. Usual Care and Nicotinamide Riboside (NR) vs. Placebo for Improving Health-related Quality of Life in Long Covid: A 2 x 2 Factorial Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05703074
• Other study ID #: 983971636
• Status: Recruiting
• Phase: Phase 2
• Start date: January 30, 2023
• Est. completion date: July 2025

Study information

• Verified date: May 2024
• Source: University Hospital, Akershus
• Contact: Vegard BB Wyller, PhD
• Phone: 91166681
• Email: v.b.b.wyller[@]medisin.uio.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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 psychosocial factors, 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 (digit span 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 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 treatments 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 310
• Est. completion date: July 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Long COVID

Intervention

Dietary Supplement:
• Nicotinamide Riboside (NR)
4 capsules (a total of 1000 mg) 2 times daily for 84 days

Behavioral:
• Mind-body reprocessing therapy (MBRT)
4-6 face-to-face meetings over 3-4 weeks, unlimited access to designated online resources.
• Care as usual
A brief self-help leaflet on long COVID is distributed, otherwise care as usual by the general practitioner

Dietary Supplement:
• Placebo
4 capsules (empty) 2 times daily for 84 days.

Locations

Country	Name	City	State
Norway	Akershus University Hospital	Lørenskog

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Akershus

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Attention bias	A computerised test of attention bias towards illness-related words	Three months after inclusion (T2)
Other	Worrying tendencies	Penn State Worry Questionnaire (PSWQ), total sum score (higher scores means more worrying)	Three months after inclusion (T2)
Other	Sympathetic predominance	Heart rate variability (HRV) indices in the time and frequency domain using a 5-minute ECG recording obtained during supine rest	Three months after inclusion (T2)
Other	Post-exertional malaise (PEM)	PEM items from the DePaul Symptom Questionnaire, total average score across five items	Three months after inclusion (T2)
Other	Pain	Brief Pain Inventory (BPI), average score	Three months after inclusion (T2)
Other	Sleep difficulties	Karolinska sleep questionnaire (KSQ), total sum score	Three months after inclusion (T2)
Other	Depression and anxiety	Hospital Anxiety and Depression Symptoms (HADS), total sum score	Three months after inclusion (T2)
Other	Smell and taste	Assessed by two singel questionnaire items; responses on a 5-point Likert scale	Three months after inclusion (T2)
Other	Executive functioning	The trail-making test of neurocognitive functioning	Three months after inclusion (T2)
Primary	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	Inflammation	Plasma levels of C-reactive protein, high-sensitive assay (hsCRP). Higher levels indicate more inflammation	Three months after inclusion (T2)
Secondary	Working memory	The Digit Span Test, total score, adopted from the Wechsler Adult Intelligence Scale (WAIS), 4th edition (WAIS-IV). Total range is from 0 - 30; higher scores indicate better working memory	Three months after inclusion (T2)
Secondary	Fatigue	Chalder Fatigue Questionnaire (CFQ), total sum score (total range is from 0 - 33; higher scores indicate more fatigue)	Three months after inclusion (T2)
Secondary	Dyspnoea	Medical Research Council dyspnoea scale. Total range is from 1 - 5, where higher scores indicate more dyspnoea	Three months after inclusion (T2)
Secondary	Global impression of change	Patient Global Impression of Change (PGIC) inventory. Total range is from 1 - 7; higher scores imply that the health status is considered worsened	Three months after inclusion (T2)
Secondary	Cost-effectiveness	Incremental cost-effectiveness ratio, using the 36-item short form (SF-36) general health subscore to determine quality-adjusted life years.	Three months after inclusion (T2)