Mental Intervention and Nicotinamide Riboside Supplementation in Long Covid (MINIRICO)

University Hospital, Akershus

Status and phase: Active, not recruiting; Phase 2

Conditions: Long COVID

Treatments: Dietary Supplement: Nicotinamide Riboside (NR); Behavioral: Care as usual; Dietary Supplement: Placebo; Behavioral: Mind-body reprocessing therapy (MBRT)

Study type: Interventional

Funder types: Other

Identifiers

NCT05703074

983971636

Details and patient eligibility

About

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).

Enrollment: 310 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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310 participants in 4 patient groups

MBRT and NR

Other group

Description:

Psychological therapy and dietary supplement

Treatment:

Behavioral: Mind-body reprocessing therapy (MBRT)

Dietary Supplement: Nicotinamide Riboside (NR)

MBRT and placebo

Other group

Description:

Psychological therapy and placebo dietary supplement

Treatment:

Behavioral: Mind-body reprocessing therapy (MBRT)

Dietary Supplement: Placebo

Care as usual and NR

Other group

Description:

No psychological therapy (information only) and dietary supplement

Treatment:

Behavioral: Care as usual

Dietary Supplement: Nicotinamide Riboside (NR)

Care as usual and placebo

Other group

Description:

No psychological therapy (information only) and placebo dietary supplement

Treatment:

Dietary Supplement: Placebo

Behavioral: Care as usual