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Improvement of the Nutritional Status Regarding Nicotinamide (Vitamin B3) and the Disease Course of COVID-19 (COVit-2)

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ClinicalTrials.gov Identifier: NCT04751604
Recruitment Status : Recruiting
First Posted : February 12, 2021
Last Update Posted : August 19, 2021
Sponsor:
Information provided by (Responsible Party):
University Hospital Schleswig-Holstein

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 frequency of complete symptom resolution after 2 weeks of supplementation. Secondary endpoints are the frequency of complete symptom resolution after 4 or 6 weeks of supplementation, the time from diagnosis to symptom resolution as well as the frequency and severity of COVID-19 symptoms, particularly also in the lower respiratory tract. The clinical WHO scale for COVID-19 and the development of severe COVID-19 are also investigated. 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 and after 2, 4 and 6 weeks. Stool samples are collected from selected patients at week 0, week 1/2, week 4, week 6 and after 6 months. In addition to blood count and standard blood profile, various inflammatory markers and the metabolome, in particular tryptophan metabolism, are examined in the blood. In these patients, the viral strain is be 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 patients) as well as metagenome and metabolome (in 20-30 patients) 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 and a cognitive test validated for phone surveys (T3MS) after 6 months will be used to investigate whether such a supplementation has any influence on the post COVID-19 syndrome.

Condition or disease Intervention/treatment Phase
COVID-19 Dietary Supplement: Nicotinamide Dietary Supplement: Placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 840 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: Improvement of the Nutritional Status Regarding Nicotinamide (Vitamin B3) and the Disease Course of COVID-19
Actual Study Start Date : February 1, 2021
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nicotinamide
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
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

Placebo Comparator: Placebo
Daily oral administration of 2 matching placebo tablets for 4 weeks
Dietary Supplement: Placebo
Daily oral administration of 2 matching placebo tablets for 4 weeks




Primary Outcome Measures :
  1. Frequency of complete symptom resolution after 2 weeks of dietary supplementation [ Time Frame: 2 weeks ]
    Symptoms are recorded during telephone interviews at baseline and at week 2 in an electronic case report form and as patient-reported outcomes by paper questionnaires (SF-36 V.1.0 and FACIT-F)


Secondary Outcome Measures :
  1. Frequency of complete symptom resolution after 4 weeks of dietary supplementation [ Time Frame: 4 weeks ]
    Symptoms are recorded during telephone interviews at baseline and at week 4 in an electronic case report form and as patient-reported outcomes by paper questionnaires (SF-36 V.1.0 and FACIT-F)

  2. Frequency of complete symptom resolution after 6 weeks (4 weeks of dietary supplementation and 2 weeks follow-up) [ Time Frame: 6 weeks ]
    Symptoms are recorded during telephone interviews at baseline and at week 6 in an electronic case report form and as patient-reported outcomes by paper questionnaires (SF-36 V.1.0 and FACIT-F)

  3. Time from diagnosis to complete symptom resolution [days] [ Time Frame: Through study completion, up to 6 months ]
    Symptoms are recorded during telephone interviews at baseline and at weeks 2, 4 and 6 as well as after 6 months in an electronic case report form and as patient-reported outcomes by paper questionnaires (SF-36 V.1.0 and FACIT-F)

  4. Frequency of individual COVID-19 symptoms at baseline, Week 2, Week 4 and Week 6 [ Time Frame: 6 weeks ]
    The following symptoms are recorded during telephone interviews at baseline and at weeks 2, 4 and 6 in an electronic case report form and explored individually: fatigue, limited physical capacity, fever (up to 39°C or above), chills, shortness of breath, whistling/wheezing, pneumonia, cough (with or without sputum production), rhinitis/rhinorrhea, sore throat/pharyngitis, hoarseness, myalgia, arthralgia, limb pain, chest pain, headache, abdominal pain, diarrhea, nausea, vomiting, loss of appetite/lower food intake, other gastrointestinal symptoms (to be named individually), impaired sense of smell, impaired sense of taste, confusion, dizziness, conjunctivitis, skin rash, hair loss, and other symptoms (to be named individually). In a subgroup of patients, daily changes in symptom severity during the time of dietary supplementation are recorded and graded: 0 = not at all, 1 = mild, 2 = moderate, 3 = severe, 4 = intolerable.

  5. Severity of symptoms of the complaint scale for lower respiratory infections at baseline, Week 2, Week 4 and Week 6 [ Time Frame: 6 weeks ]

    Symptoms are recorded during telephone interviews at baseline and at weeks 2, 4 and 6 in an electronic case report form.

    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 activity, and general feeling of illness, with the following gradations: 0 = normal, 1 = very minor problem, 2 = minor problem, 3 = moderately poor, 4 = poor, 5 = very poor, 6 = maximally poor.



Other Outcome Measures:
  1. World Health Organization (WHO) COVID-19 Ordinal Scale for Clinical Improvement at baseline, Week 2, Week 4 and Week 6 [ Time Frame: 6 weeks ]
    See https://www.who.int/publications/i/item/covid-19-therapeutic-trial-synopsis. Symptoms are recorded during telephone interviews at baseline and at weeks 2, 4 and 6 in an electronic case report form.

  2. 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) [ Time Frame: Through study completion, up to 6 months ]

    Frequency of severe COVID-19, defined as achieving one of the following characteristics:

    1. examination in an emergency department;
    2. hospitalisation with continuous oxygen requirement of at least 24 hours;
    3. intensive care requirement;
    4. ventilation requirement;
    5. death by COVID-19.

    Characteristics are recorded during telephone interviews at baseline and at weeks 2, 4 and 6 as well as after 6 months in an electronic case report form; if necessary, the records are completed by data from the attending physicians, for which informed consent is given prior to enrolment into the trial


  3. Comparison between findings from the pilot phase of the study and the second part of the study [ Time Frame: Through study completion, up to 6 months ]
    Symptoms are recorded during telephone interviews at baseline and at weeks 2, 4 and 6 as well as after 6 months in an electronic case report form

  4. Changes in fatigue (eCRF) [ Time Frame: Through study completion, up to 6 months ]
    Symptoms are recorded during telephone interviews at baseline and at weeks 2, 4 and 6 as well as after 6 months in an electronic case report form

  5. Changes in fatigue (FACIT-F) [ Time Frame: Through study completion, up to 6 months ]
    Symptoms are recorded at baseline and at weeks 2, 4 and 6 as well as after 6 months as patient-reported outcomes by paper questionnaires (FACIT-F)

  6. Changes in quality of life (eCRF) [ Time Frame: Through study completion, up to 6 months ]
    Parameters relevant for quality of life are recorded during telephone interviews at baseline and at weeks 2, 4 and 6 as well as after 6 months in an electronic case report form

  7. Changes in quality of life (SF-36 V.1.0) [ Time Frame: Through study completion, up to 6 months ]
    Parameters relevant for quality of life are recorded at baseline and at weeks 2, 4 and 6 as well as after 6 months as patient-reported outcomes by paper questionnaires (SF-36 V.1.0)

  8. Changes in blood levels of tryptophan [ Time Frame: Through study completion, up to 6 months ]
    Blood levels are measured at baseline and at weeks 2, 4 and 6 as well as after 6 months (in selected patients)

  9. Changes in blood levels of tryptophan metabolites [ Time Frame: Through study completion, up to 6 months ]
    Blood levels are measured at baseline and at weeks 2, 4 and 6 as well as after 6 months (in selected patients)

  10. Changes in blood levels of inflammatory markers (C-reactive protein, interleukin-6, ferritin, neopterin, D-dimers) [ Time Frame: Through study completion, up to 6 months ]
    Blood levels are measured at baseline and at weeks 2, 4 and 6 as well as after 6 months (in selected patients)

  11. Changes in blood count and standard blood profile [ Time Frame: Through study completion, up to 6 months ]
    Blood count and standard blood profile are measured at baseline and at weeks 2, 4 and 6 as well as after 6 months (in selected patients)

  12. Changes in blood metabolome composition [ Time Frame: Through study completion, up to 6 months ]
    Blood metabolome composition is measured at baseline and at weeks 2, 4 and 6 as well as after 6 months (in selected patients). Targeted metabolomics will be performed using a commercial kit for the identification of approx. 600 metabolites (MxP Quant 500, Biocrates, Innsbruck, Austria)

  13. Strain of SARS-CoV-2 virus [ Time Frame: 2 weeks, preferably at baseline ]
    Sequencing of SARS-CoV-2 virus from nasopharyngeal swab samples (in selected patients)

  14. Changes in stool microbiome composition [ Time Frame: Through study completion, up to 6 months ]
    Stool microbiome composition is measured at baseline and at weeks 2, 4 and 6 as well as after 6 months (in selected patients). DNA will be isolated from fecal samples using DNeasy PowerSoil Kit (Qiagen), the V3-V4 region of the 16S gene amplified and barcoded amplicons will be sequenced on an Illumina MiSeq (2 x 300 nt) with >10,000 reads per sample. Reads passing quality control will be paired-end assembled and after rarefaction to normalize for sequencing depth using QIIME2 data analysis will be performed, i.e. alpha and beta diversity, taxonomic summaries, differential features, indicator analyses and correlation with metadata

  15. Changes in stool metagenome composition [ Time Frame: Through study completion, up to 6 months ]
    Stool metagenome composition is measured at baseline and at weeks 2, 4 and 6 as well as after 6 months (in selected patients). DNA will be isolated from fecal samples using DNeasy PowerSoil Kit (Qiagen) and sequenced on an Illumina NovaSeq 6000 using NexteraXT with 2 x 125 bp and 20x coverage. After quality filtering (removal of low-quality reads, 3' trimming, removal of reads from human DNA) MEtaGenome Analyser (MEGAN) will be used for taxonomic classification of metagenomic reads and the reads will be de novo assembled into contigs using Metagenomic Data Utilization and Analysis (MEDUSA) and then annotated to genes and functions in the Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Groups (COG) and Pfam for functional analysis

  16. Changes in stool metabolome composition [ Time Frame: Through study completion, up to 6 months ]
    Stool metabolome composition is measured at baseline and at weeks 2, 4 and 6 as well as after 6 months (in selected patients). Targeted metabolomics will be performed using a commercial kit for the identification of approx. 600 metabolites (MxP Quant 500, Biocrates, Innsbruck, Austria)

  17. Frequency and severity of symptoms characteristic of post-COVID-19 syndrome at 6 months [ Time Frame: 6 months ]
    A validated smell test (Smell Identification Test™; Sensonics / MediSense) is performed by the patient and recorded as patient-reported outcome by a paper questionnaire. Questionnaires on olfactory and gustatory abilities (incl. Questionnaire of Olfactory Disorders, QOD), respiration (Multidimensional Dyspnoea Profile, MDP), mental state (Patient Health Questionnaire Depression, PHQ-8; Generalised Anxiety Disorder 7, GAD-7; Perceived Stress Scale, PSS; Brief Resilience Scale, BRS), sleep quality (Pittsburgh Sleep Quality Index, PSQI) and fatigue (Multidimensional Fatigue Inventory, MFI) are recorded as patient-reported outcomes by paper questionnaires. In addition, a cognition test (T3MS) validated for telephone interviews will be performed.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

- Vaccination against SARS-CoV-2.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04751604


Contacts
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Contact: Stefan Schreiber, MD +49 431 500 ext 22201 s.schreiber@mucosa.de
Contact: Matthias Laudes, MD +49 431 500 ext 22217 matthias.laudes@uksh.de

Locations
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Germany
University Hospital Schleswig-Holstein Recruiting
Kiel, Schleswig-Holstein, Germany, 24105
Contact: Stefan Schreiber, MD    +49 431 500 ext 22201    s.schreiber@mucosa.de   
Contact: Matthias Laudes, MD    +49 431 500 ext 22217    matthias.laudes@uksh.de   
Sponsors and Collaborators
University Hospital Schleswig-Holstein
Investigators
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Principal Investigator: Stefan Schreiber, MD University Hospital Schleswig-Holstein
Additional Information:
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Responsible Party: University Hospital Schleswig-Holstein
ClinicalTrials.gov Identifier: NCT04751604    
Other Study ID Numbers: A 107/20
First Posted: February 12, 2021    Key Record Dates
Last Update Posted: August 19, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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COVID-19
Disease Progression
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Niacinamide
Niacin
Nicotinic Acids
Vitamin B Complex
Vitamins
Micronutrients
Physiological Effects of Drugs
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents