MINIRICO: Mental Intervention and Nicotinamide Riboside Supplementation in Long Covid
Study Details
Study Description
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 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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: MBRT and NR Psychological therapy and dietary supplement |
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.
|
| Other: MBRT and placebo Psychological therapy and placebo dietary supplement |
Behavioral: Mind-body reprocessing therapy (MBRT)
4-6 face-to-face meetings over 3-4 weeks, unlimited access to designated online resources.
Dietary Supplement: Placebo
4 capsules (empty) 2 times daily for 84 days.
|
| Other: Care as usual and NR No psychological therapy (information only) and dietary supplement |
Dietary Supplement: Nicotinamide Riboside (NR)
4 capsules (a total of 1000 mg) 2 times daily for 84 days
Behavioral: Care as usual
A brief self-help leaflet on long COVID is distributed, otherwise care as usual by the general practitioner
|
| Other: Care as usual and placebo No psychological therapy (information only) and placebo dietary supplement |
Behavioral: 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.
|
Outcome Measures
Primary Outcome Measures
- 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
- Inflammation [Three months after inclusion (T2)]
Plasma levels of C-reactive protein, high-sensitive assay (hsCRP). Higher levels indicate more inflammation
- Working memory [Three months after inclusion (T2)]
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
- 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 1 - 5, 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.
Other Outcome Measures
- Attention bias [Three months after inclusion (T2)]
A computerised test of attention bias towards illness-related words
- Worrying tendencies [Three months after inclusion (T2)]
Penn State Worry Questionnaire (PSWQ), total sum score (higher scores means more worrying)
- Sympathetic predominance [Three months after inclusion (T2)]
Heart rate variability (HRV) indices in the time and frequency domain using a 5-minute ECG recording obtained during supine rest
- Post-exertional malaise (PEM) [Three months after inclusion (T2)]
PEM items from the DePaul Symptom Questionnaire, total average score across five items
- Pain [Three months after inclusion (T2)]
Brief Pain Inventory (BPI), average score
- Sleep difficulties [Three months after inclusion (T2)]
Karolinska sleep questionnaire (KSQ), total sum score
- Depression and anxiety [Three months after inclusion (T2)]
Hospital Anxiety and Depression Symptoms (HADS), total sum score
- Smell and taste [Three months after inclusion (T2)]
Assessed by two singel questionnaire items; responses on a 5-point Likert scale
- Executive functioning [Three months after inclusion (T2)]
The trail-making test of neurocognitive functioning
Eligibility Criteria
Criteria
Inclusion Criteria:
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Undergone acute COVID-19, confirmed EITHER by a positive PCR-test OR a positive self-test combined with confirmatory antibody-pattern in blood.
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Persistent symptoms at least 6 months following acute COVID-19 without symptom-free interval.
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Functional disability to an extent that impacts negatively on normal activities (such as work attendance, physical exercise, social activities, etc.)
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Informed consent
Exclusion Criteria:
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Other chronic illnesses, demanding life situations or concomitant drug use/substance abuse that is considered a plausible cause of persistent symptoms and associated disability
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Sustained organ damage (lung, heart, brain) following acute, serious Covid-19
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Pregnancy.
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Bedridden
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Insufficient command of Norwegian
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- University Hospital, Akershus
Investigators
- Study Chair: Torbjørn Omland, PhD, Akershus University Hospital/University of Oslo
Study Documents (Full-Text)
More Information
Publications
None provided.- 983971636