Kinetics and Metabolism of Nicotinamide Provided as a Dietary Supplementation

University Hospital Schleswig-Holstein28 enrolled

Overview

The diet of patients with reduced tryptophan serum levels that are either hospitalized for acute respiratory infection or treated for chronic inflammatory diseases such as inflammatory bowel diseases (in- or outpatients) is supplemented with controlled-ileocolonic-release nicotinamide (CICR-NAM) at doses of 500 mg or 1000 mg per day for four weeks. In the COVit-2 trial (NCT04751604), nicotinamide supplementation including CICR-NAM has been shown to accelerate physical recovery from mild-to-moderate COVID-19 (for publication, see References). The main objective of this open-label case series is to investigate the pharmacokinetics and metabolism of nicotinamide in patients with more severe respiratory infections or chronic inflammatory conditions. In addition, patients can optionally provide information on their quality of life and fatigue status.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Respiratory Infection (for Example, Pneumonia, Bronchitis)Respiratory Infection Virus Community Acquired Pneumonia (CAP)

Interventions

Controlled-ileocolonic-release nicotinamide (CICR-NAM): 500 mg/dDIETARY_SUPPLEMENT

Controlled-ileocolonic-release nicotinamide (CICR-NAM) film-coated tablets release 500 mg nicotinamide per tablet at a pH of 7, leading to a delayed and prolonged systemic exposure to nicotinamide and to exposure of the ileum and colon including the gut microbiome.

Controlled-ileocolonic-release nicotinamide (CICR-NAM): 1000 mg/dDIETARY_SUPPLEMENT

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Serum tryptophan levels below normal range. * Acute, infectious respiratory disease requiring treatment (e.g. proven acute SARS-CoV-2 or influenza virus infection with inpatient treatment) or chronic inflammatory disease (e.g. chronic inflammatory bowel disease) in remission or in acute relapse (outpatient or inpatient treatment). Exclusion Criteria: * Inability to give informed consent. * Pregnancy or breastfeeding. * Serious other illness, e.g. cancer. * Anemia: Hb \<10 mg/dL. * Intake of medication to raise the pH value in the stomach (e.g. proton pump inhibitors, H2 receptor antagonists or antacids) in higher doses over a longer period of time.

Outcomes

Primary Outcomes

Changes in plasma concentrations of nicotinamide (NAM) and its main metabolites N-methylnicotinamide (NMN) and N-methyl-2-pyridone-5-carboxamide (2-Py) as well as nicotinic acid (NA) and nicotinuric acid (NUA)

Simultaneous measurement by liquid chromatography with tandem mass spectrometry.

Time frame: From baseline (day 1) until day 2 (minimum), day 3 or day 8

Secondary Outcomes

Changes in serum concentrations of tryptophan and its metabolites

Simultaneous measurement by liquid chromatography with tandem mass spectrometry.

Time frame: From baseline (day 1) until day 2 (minimum), day 3 or day 8

Changes in quality of life (EuroQoL 5 Dimensions 5 Levels [EQ-5D-5L] questionnaire; optional)

The EQ-5D-5L health states can be summarised using a 5-digit code representing the 5 dimensions 'mobility', 'self-care', 'activity', 'pain' and 'anxiety' with 5 levels each from 1 = no problem to 5 = maximum problem. In addition, the subjects report their overall self-perceived health-related quality of life using the Visual Analogue Scale (VAS) from 0 = worst health one can imagine to 100 = best health one can imagine.

Time frame: Weekly from baseline until week 4

Changes in fatigue (Functional Assessment of Chronic Illness Therapy - Fatigue [FACIT-F] questionnaire; optional)

The FACIT-F questionnaire is a 40-item measure that assesses self-reported fatigue and its impact upon daily activities and function. The higher the subscores and total score, the better the self-perceived quality of life (for the total score, the range is from 0 to 160).