Clinical trial NCT04751604: Improvement of the Nutritional Status Regarding Nicotinamide (Vitamin B3) and the Disease Course of COVID-19
Official title: Improvement of the Nutritional Status Regarding Nicotinamide (Vitamin B3) and the Disease Course of COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COVID-19
Lead sponsor: University Hospital Schleswig-Holstein
Sponsor class: OTHER
First posted: 2021-02-12
Enrollment: 900
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Based on the literature, it seems likely that a nutritional intervention with nicotinamide (a form of vitamin B3) can support the therapy of SARS-CoV-2 infection (COVID-19). A pilot phase of the COVit trial showed an effect of nicotinamide on the time to complete resolution of COVID-19 symptoms. In addition, diarrhoea is a common symptom of COVID-19. Therefore, in a second part of the study, 420 symptomatic patients each with confirmed SARS-CoV-2 infection are to take 1,000 mg nicotinamide (500 mg conventional nicotinamide and 500 mg nicotinamide released in a controlled manner in the intestine) or corresponding placebos per day in a blinded fashion for 4 weeks. The primary endpoint of the trial is the occurrence of individual COVID-19 symptoms over time (primary analysis time point: week 2). Secondary endpoints focus on the severity of COVID-19 symptoms, the post-COVID-19 syndrome (PCS), anti-SARS-CoV-2 antibody levels, and the time to resolution of individual or all symptoms. Exploratory endpoints include the WHO clinical scale for COVID-19, development of severe COVID-19, fatigue, quality of life and biomarkers. Patients are approached after positive testing and give their informed consent online. After randomised distribution of the trial supplements, patients are interviewed by telephone about their disease course at baseline (week 0), week 2, week 4, week 6 and after 6 months. Stool samples are collected from up to 400 patients at the same timepoints. In addition to blood count and standard blood profile, various inflammatory markers and the metabolome, in particular tryptophan metabolism, are examined in the blood of up to 20 selected patients. In these patients, the viral strain is determined by sequencing from nasopharyngeal swabs. In selected patients, short-term pharmacokinetics of nicotinamide, nicotinic acid and nicotinuric acid as well as of metabolites of nicotinamide and tryptophan are investigated. In the stool, changes in the microbiome (in 100-300 patients) as well as metagenome and metabolome (in a subgroup) will be analysed. The study is expected to produce rapid results on whether nicotinamide supplementation can alleviate the disease course of COVID-19. Moreover, a follow-up interview, a smell test, a cognitive test and anti-SARS-CoV-2 antibody levels after at least 6 months will be used to investigate whether the supplementation has any influence on PCS as well as the immune reaction against SARS-CoV-2.


Eligibility criteria: Inclusion Criteria:

* The patient is of age (at least 18 years).
* SARS-CoV-2 infection confirmed by laboratory findings; the positive test must not date back more than 7 days.
* Relevant infection symptoms, e.g. in the respiratory or gastrointestinal tract.
* The patient has been able to give written consent via a website before any trial procedure is performed and can comply with the trial-dependent prerequisites and requirements.

Exclusion Criteria:

* Current participation in another trial.
* Pregnancy or breastfeeding.
* Vaccination against SARS-CoV-2.

Primary outcomes:
measure: Frequencies of individual COVID-19 symptoms at week 0, week 2 (primary time of analysis), week 4 and week 6 as well as after 6 months.
timeFrame: Through study completion, up to 6 months
Secondary outcomes:
measure: Severity of individual COVID-19 symptoms at week 0, week 2 (primary time of analysis), week 4 and week 6 as well as after 6 months.
timeFrame: Through study completion, up to 6 months
measure: Frequency and severity of symptoms characteristic of post-COVID-19 syndrome (at month 6).
timeFrame: 6 months
measure: 3. Levels of antibodies directed against the N protein or S protein of SARS-CoV-2 after at least 6 months (anti-S protein stratified for presence and type of booster vaccination).
timeFrame: 6 months
measure: Frequency of complete symptom resolution after 2 weeks of dietary supplementation.
timeFrame: 2 weeks
measure: Frequency of complete symptom resolution after 4 weeks of dietary supplementation.
timeFrame: 4 weeks
measure: Frequency of complete symptom resolution after 6 weeks (4 weeks of dietary supplementation and 2 weeks follow-up).
timeFrame: 6 weeks
measure: Time from diagnosis resolution of individual symptoms [days].
timeFrame: 6 weeks
measure: Time from diagnosis to complete symptom resolution [days].
timeFrame: 6 weeks
Other outcomes:
measure: World Health Organization (WHO) COVID-19 Ordinal Scale for Clinical Improvement at baseline, Week 2, Week 4 and Week 6 as well as after 6 months.
timeFrame: Through study completion, up to 6 months
measure: Frequency of severe COVID-19 (examination in an emergency department / hospitalisation with requirement for oxygen (at least 24 h), intensive care or ventilation / death by COVID-19).
timeFrame: Through study completion, up to 6 months
measure: Comparison between findings from the pilot phase of the study and the second part of the study.
timeFrame: Through study completion, up to 6 months
measure: Changes in fatigue (eCRF).
timeFrame: Through study completion, up to 6 months
measure: Changes in fatigue (FACIT-F).
timeFrame: Through study completion, up to 6 months
measure: Changes in quality of life (eCRF).
timeFrame: Through study completion, up to 6 months
measure: Changes in quality of life (SF-36 V.1.0).
timeFrame: Through study completion, up to 6 months
measure: Changes in blood levels of tryptophan.
timeFrame: Through study completion, up to 6 months
measure: Changes in blood levels of tryptophan metabolites.
timeFrame: Through study completion, up to 6 months
measure: Changes in blood levels of inflammatory markers (C-reactive protein, interleukin-6, ferritin, neopterin, D-dimers).
timeFrame: Through study completion, up to 6 months
measure: Changes in blood count and standard blood profile.
timeFrame: Through study completion, up to 6 months
measure: Changes in blood metabolome composition.
timeFrame: Through study completion, up to 6 months
measure: Strain of SARS-CoV-2 virus.
timeFrame: 2 weeks, preferably at baseline
measure: Changes in stool microbiome composition.
timeFrame: Through study completion, up to 6 months
measure: Changes in stool metagenome composition.
timeFrame: Through study completion, up to 6 months
measure: Changes in stool metabolome composition.
timeFrame: Through study completion, up to 6 months
measure: Short-term pharmacokinetics.
timeFrame: 3 days
Locations:
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein
state: Schleswig-Holstein
Study officials:
affiliation: University Hospital Schleswig-Holstein
name: Stefan Schreiber, MD
role: PRINCIPAL_INVESTIGATOR
References: