Clinical trial NCT05703074: Mental Intervention and Nicotinamide Riboside Supplementation in Long Covid
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Long COVID
Lead sponsor: University Hospital, Akershus
Sponsor class: OTHER
First posted: 2023-01-27
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Health-related quality of life
timeFrame: Three months after inclusion (T2)
Secondary outcomes:
measure: Inflammation
timeFrame: Three months after inclusion (T2)
measure: Executive functioning
timeFrame: Three months after inclusion (T2)
measure: Fatigue
timeFrame: Three months after inclusion (T2)
measure: Dyspnoea
timeFrame: Three months after inclusion (T2)
measure: Global impression of change
timeFrame: Three months after inclusion (T2)
measure: Cost-effectiveness
timeFrame: Three months after inclusion (T2)
Other outcomes:
measure: Subjective cognitive difficulties
timeFrame: Three months after inclusion (T2)
measure: Worrying tendencies
timeFrame: Three months after inclusion (T2)
measure: Sympathetic predominance
timeFrame: Three months after inclusion (T2)
measure: Post-exertional malaise (PEM)
timeFrame: Three months after inclusion (T2)
measure: Subjective pain experiences
timeFrame: Three months after inclusion (T2)
measure: Sleep difficulties
timeFrame: Three months after inclusion (T2)
measure: Depression
timeFrame: Three months after inclusion (T2)
measure: Smell and taste abnormalities
timeFrame: Three months after inclusion (T2)
measure: Working memory
timeFrame: Three months after inclusion (T2)
measure: Inflammation, additional information
timeFrame: Three months after inclusion (T2)
measure: Anxiety
timeFrame: Three months after inclusion (T2)
measure: Physical functioning
timeFrame: Three months after inclusion (T2)
measure: Social functioning
timeFrame: Three months after inclusion (T2)
Locations:
city: Lørenskog
country: Norway
facility: Akershus University Hospital
Study officials:
affiliation: Akershus University Hospital/University of Oslo
name: Torbjørn Omland, PhD
role: STUDY_CHAIR
References: