Improvement of the Nutritional Status Regarding Nicotinamide (Vitamin B3) and the Disease Course of COVID-19

NCT04751604 | Completed

• 1 other identifier: A 107/20
• Study Type: interventional
• Target: 900
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (1)

• 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.

  A broad range of symptoms is recorded during telephone interviews at baseline, at weeks 2, 4 and 6 and after 6 months in an electronic case report form. Key symptoms include performance drop / limited physical capacity, the ability to perform normal activities, cough and fatigue. A complaint scale for lower respiratory tract infections is queried with the aspects of cough, mucus production, shortness of breath, sleep, ability to perform normal activities, and general feeling of illness, with gradations from 0 = normal to 6 = maximally poor. In addition, patient-reported outcomes by paper questionnaires are recorded: SF-36 V.1.0 and FACIT-F are completed in parallel to the telephone interviews from baseline to through study completion (up to 6 months); a subgroup of patients records daily changes in symptom occurrence and severity during the time of dietary supplementation (4 weeks), with gradations from 0 = not at all to 4 = intolerable.

  Through study completion, up to 6 months

Secondary Outcomes (8)

• 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.

  Through study completion, up to 6 months

• Frequency and severity of symptoms characteristic of post-COVID-19 syndrome (at month 6).

  6 months

• 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).

  6 months

• Frequency of complete symptom resolution after 2 weeks of dietary supplementation.

  2 weeks

• Frequency of complete symptom resolution after 4 weeks of dietary supplementation.

  4 weeks

Other Outcomes (17)

• 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.

  Through study completion, up to 6 months

• 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).

  Through study completion, up to 6 months

• Comparison between findings from the pilot phase of the study and the second part of the study.

  Through study completion, up to 6 months

Study Arms (2)

Nicotinamide

EXPERIMENTAL

Daily oral administration of 1,000 mg nicotinamide \[1x 500-mg conventional nicotinamide tablet and 1x 500-mg tablet with controlled-ileocolonic-release nicotinamide (CICR-NAM)\] for 4 weeks

Dietary Supplement: Nicotinamide

Placebo

PLACEBO COMPARATOR

Daily oral administration of 2 matching placebo tablets for 4 weeks

Dietary Supplement: Placebo

Interventions

Nicotinamide DIETARY_SUPPLEMENT

Daily oral administration of 1,000 mg nicotinamide \[1x 500-mg conventional nicotinamide tablet and 1x 500-mg tablet with controlled-ileocolonic-release nicotinamide (CICR-NAM)\] for 4 weeks

Nicotinamide

Placebo DIETARY_SUPPLEMENT

Daily oral administration of 2 matching placebo tablets for 4 weeks

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital Schleswig-Holstein: lead

Study Sites (1)

University Hospital Schleswig-Holstein

Kiel, Schleswig-Holstein, 24105, Germany

Location

MeSH Terms

Conditions

COVID-19

Interventions

Niacinamide

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Stefan Schreiber, MD

  University Hospital Schleswig-Holstein

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2021
• First Posted: February 12, 2021
• Study Start: February 1, 2021
• Primary Completion: July 27, 2022
• Study Completion: October 20, 2022
• Last Updated: November 8, 2022

Record last verified: 2022-11

Locations

DE (1)