Clinical trial NCT06674018: Indole-3-PROpionic Acid Clinical Trials - a Pilot Study
Official title: Indole-3-PROpionic Acid Clinical Trials - a Pilot Study (iPROACT-pilot)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: Indole-3-propionic acid
gut bacterial metabolite
regulatory T cells
brain-derived neurotrophic factor
dietary supplement
Lead sponsor: Glostrup University Hospital, Copenhagen
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: University of Southampton
First posted: 2024-11-05
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this pilot intervention trial is to investigate the biological effects of daily supplementation with different doses of indole-3-propionic acid (IPA) in healthy adults. The main scientific questions are:

* Does supplementation with IPA increase the abundance regulatory T cells in the blood? Regulatory T cells are believed to play an important role in preventing autoimmune diseases.
* Does supplementation with IPA increase the concentration of brain-derived neurotrophic factor (BDNF) in the blood? BDNF is believed to play an important role in maintaining brain health.
* Does supplementation with IPA affect blood analyses commonly performed to assess the risk of metabolic disorders like type 2 diabetes and cardiovascular diseases?
* How big a dose of IPA is necessary to achieve the above benefits?

Participants will:

* Take 50 mg IPA or 120 mg IPA or 500 mg IPA or placebo every morning for 14 days.
* Visit the clinic at the beginning (day 1) and at the end (day 15) of IPA supplementation to deliver blood, urine and fecal samples, have simple measurements performed, fulfil questionnaires and report any side effects.

Detailed description: Indole-3-propionic acid (IPA) is a gut bacterial metabolite with the amino acid tryptophan as substrate. In vitro and animal studies, suggest that IPA could contribute to regulating inflammation and metabolic function, preventing oxidative damage and upregulating expression of brain-derived neurotrophic factor. With this study we aim to investigate the biochemical effects of IPA at supraphysiological levels in humans.

Eligibility criteria: Inclusion Criteria:

* Healthy women and men ≥18 and ≤65 years of age
* Deemed mentally and physically able to participate

Exclusion Criteria:

* Diagnosis of gut-, heart-, liver-, kidney or immune-related disorders
* Use of antibiotics within the last month
* Pregnant or lactating women or birth within the last five months
* Use of medicine that requires prescription

Primary outcomes:
measure: Regulatory T cells (first primary outcome)
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis).
measure: Brain-derived neurotrophic factor (second primary outcome)
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis).
Secondary outcomes:
measure: Flowcytometric profiling of T cells
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis).
measure: CRP
timeFrame: Results from blood samples taken on day 15 (just before last supplement/placebo dosis) and adjusted for results from day 1 (just before first supplement/placebo dosis).
measure: Triglycerides
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis).
measure: non-HDL cholesterol
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis).
measure: C-peptide
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis).
measure: Fasting glucose
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis).
measure: Isoprostane-F2-alpha
timeFrame: Results from samples taken on day 15 and adjusted for results from day 1.
measure: 8-oxo-dG
timeFrame: Results from samples taken on day 15 and adjusted for results from day 1.
measure: Serum metabolomics
timeFrame: Four samples in total. Day 1 prior to and again 1.5 hour after intake of first capsule of IPA/ placeblo. Day 15 prior to and again 1.5 hour after intake of last capsule of IPA/ placebo.
measure: Total cholesterol
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis).
measure: VLDL cholesterol
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis).
measure: LDL cholesterol
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis).
measure: HDL cholesterol
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis).
measure: Malondialdehyde
timeFrame: Results from samples taken on day 15 and adjusted for results from day 1.
measure: Protein carbonyls
timeFrame: Results from samples taken on day 15 and adjusted for results from day 1.
measure: Glycated hemoglobin (HbA1c)
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis).
measure: Changes in the gut microbiome
timeFrame: Fecal samples are collected at three time points: prior to supplementation (earliest 48 hours prior to first visit (day 1)), short after initiation of supplementation (day 3 or soonest thereafter) and again earliest 48 hours prior to last visit.
measure: Characterization of the metabolic activity of the gut microbiota
timeFrame: Fecal samples are collected at three time points: prior to supplementation (earliest 48 hours prior to first visit (day 1)), short after initiation of supplementation (day 3 or soonest thereafter) and again earliest 48 hours prior to last visit.
measure: Bacterial polysaccharides
timeFrame: Results from samples taken on day 15 and adjusted for results from day 1.
measure: Pre-haptoglobin 2
timeFrame: Results from samples taken on day 15 and adjusted for results from day 1.
measure: Intestinal fatty acid binding protein
timeFrame: Results from samples taken on day 15 and adjusted for results from day 1.
measure: Citrulline
timeFrame: Results from samples taken on day 15 and adjusted for results from day 1.
measure: Calprotectin
timeFrame: Results from samples taken on day 15 and adjusted for results from day 1.
measure: Neopterin
timeFrame: Results from samples taken on day 15 and adjusted for results from day 1.
measure: suPAR
timeFrame: Results from samples taken on day 15 and adjusted for results from day 1.
measure: Microvesicles
timeFrame: Results from samples taken on day 15 and adjusted for results from day 1.
measure: Endothelial progenitor cells
timeFrame: Results from samples taken on day 15 and adjusted for results from day 1.
Other outcomes:
measure: Gastrointestinal comfort
timeFrame: Gastrointestinal symptoms are assessed on day 1 and day 15.
measure: Gastrointestinal transit time
timeFrame: Maize is ingested five days before visit 1 and again five days before visit 2.
measure: Stool consistency
timeFrame: Bristol stool chart is used in association with each maize test and collection of fecal samples (earliest 48 hours prior to first visit and day 3 or soonest thereafter and again earliest 48 hours prior to last visit (day 15)).
measure: Fecal pH
timeFrame: Fecal samples are collected at three time points: prior to supplementation (earliest 48 hours prior to first visit (day 1)), short after initiation of supplementation (day 3 or soonest thereafter) and again earliest 48 hours prior to last visit (day 15).
measure: Antibody-coating of bacteria
timeFrame: Fecal samples are collected at three time points: prior to supplementation (earliest 48 hours prior to first visit (day 1)), short after initiation of supplementation (day 3 or soonest thereafter) and again earliest 48 hours prior to last visit (day 15).
measure: Immunoglobulin G
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (just before first supplement/placebo dosis).
measure: Immunoglobulin A
timeFrame: Results from blood samples taken on day 15 (just before last supplement/placebo dosis) and adjusted for results from day 1 (just before first supplement/placebo dosis).
measure: Leucocyte counts
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (just before first supplement/placebo dosis).
measure: Hemoglobin
timeFrame: Results from blood samples taken on day 15 (just before last supplement/placebo dosis) and adjusted for results from day 1 (just before first supplement/placebo dosis).
measure: Alanine transaminase
timeFrame: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis).
measure: Alkaline phosphatase
timeFrame: Results from blood samples taken on day 15 (just before last supplement/placebo dosis) and adjusted for results from day 1 (just before first supplement/placebo dosis).
measure: Aspartate aminotransferase
timeFrame: Results from blood samples taken on day 15 (just before last supplement/placebo dosis) and adjusted for results from day 1 (just before first supplement/placebo dosis).
measure: Bilirubin
timeFrame: Results from blood samples taken on day 15 (just before last supplement/placebo dosis) and adjusted for results from day 1 (just before first supplement/placebo dosis).
measure: Coagulation factors II + VII + X
timeFrame: Results from blood samples taken on day 15 (just before last supplement/placebo dosis) and adjusted for results from day 1 (just before first supplement/placebo dosis).
measure: Lactate dehydrogenase (LDH)
timeFrame: Results from blood samples taken on day 15 (just before last supplement/placebo dosis) and adjusted for results from day 1 (just before first supplement/placebo dosis).
measure: Creatinine
timeFrame: Results from blood samples taken on day 15 (just before last supplement/placebo dosis) and adjusted for results from day 1 (just before first supplement/placebo dosis)
measure: eGFR
timeFrame: Results from blood samples taken on day 15 (just before last supplement/placebo dosis) and adjusted for results from day 1 (just before first supplement/placebo dosis).
measure: Albumin
timeFrame: Results from blood samples taken on day 15 (just before last supplement/placebo dosis) and adjusted for results from day 1 (just before first supplement/placebo dosis).
measure: 25-OH-vitamin D
timeFrame: Results from blood samples taken on day 15 (just before last supplement/placebo dosis) and adjusted for results from day 1 (just before first supplement/placebo dosis).
measure: Blood pressure
timeFrame: Measured on day 1 and then again on day 15
Locations:
city: Glostrup
country: Denmark
facility: Optic Neuritis Clinic, Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet-Glostrup
Study officials:
affiliation: Jette Lautrup Frederiksen
name: Jette Lautrup Frederiksen, Prof, DMSc, MD
role: PRINCIPAL_INVESTIGATOR
References: