Indole-3-PROpionic Acid Clinical Trials - a Pilot Study
- Conditions
- Healthy
- Registration Number
- NCT06674018
- Lead Sponsor
- Glostrup University Hospital, Copenhagen
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 79
- Healthy women and men ≥18 and ≤65 years of age
- Deemed mentally and physically able to participate
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Regulatory T cells (first primary outcome) Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis). FoxP3+CD25+CD127- regulatory T cells expressed as a percentage of single, live CD3+CD4+CD8- lymphocytes. Analysed in freshly isolated peripheral blood mononuclear cells using a Symphony A3 flowcytometer.
Brain-derived neurotrophic factor (second primary outcome) Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis). Brain-derived neurotrophic factor measured in plasma samples using ELISA or mesoscale.
- Secondary Outcome Measures
Name Time Method Flowcytometric profiling of T cells Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis). T cell profiling of freshly isolated peripheral blood mononuclear cells using a Symphony A3 flowcytometer. Panel antigens: CD3, CD4, CD8, CD45RA, CCR7, CXCR3, CCR6, CCR4, CCR10, CD25, CD127, FoxP3.
Target populations Th1: CXCR3+CCR4-CCR6-CCR10- Th2: CXCR3-CCR4+CCR6-CCR10- Th17: CXCR3-CCR4+CCR6+CCR10- Th17.1: CXCR3+CCR4-CCR6+CCR10- Th22: CXCR3-CCR4+CCR6+CCR10+ all of the above expressed as a percentage of single, live CD3+CD4+CD8-CD45RA- lymphocytes.
Furthermore, Th1/Th2 and Th17/Treg ratios will be calculated and the expression of CCR7 will be analysed within the target populations.
In addition, the expression of the above chemokine receptors will be explored within the population of FoxP3+CD25+C1D127- T regulatory cells. This will allow for monitoring of newly identified T cells subsets such as Th1-like Tregs.
Lastly, an untargetted approach may be employed to allow for unbiased identification of changes in novel, yet uncharacterized populations.CRP 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). C-reactive protein (CRP) measured in plasma (mg/L) as a biomarker of infection and systemic inflammation. Lower-limit of quantification: 0,4 mg/L. Values below 0,4 mg/L are imputed as 0,2 mg/L.
Triglycerides Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis). Plasma triglycerides (mmol/l).
non-HDL cholesterol Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis). Non-HDL cholesterol calculated as total cholesterol minus HDL cholesterol (mmol/l)
C-peptide Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis). Proinsulin C-peptide (pmol/l) measured in plasma.
Fasting glucose Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis). Plasma glucose (mmol/l). Participants abstain from eating and drinking after 22.00 the day before. Only water is allowed. Fasting blood samples are taken between 8.00-10.00 in the morning.
Isoprostane-F2-alpha Results from samples taken on day 15 and adjusted for results from day 1. Isoprostane-F2-alpha measured in blood or morningurine samples as a marker of lipid oxidation.
8-oxo-dG Results from samples taken on day 15 and adjusted for results from day 1. 8-oxo-dG (8-Oxo-2'-deoxyguanosine) measured in blood or morningurine samples as a marker of DNA-related stress damage.
Serum metabolomics 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. Targetted and untargetted liquid-chromatography mass-spectrometry-based metabolomics of serum samples. Targetted analyses aim to quantify indole-3-propionic acid and its metabolites (biomarker of compliance as well as absorptive and metabolic capacity), other bacterial- and host metabolites of tryptophan as well as short-chain fatty acids.
Total cholesterol Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis). Plasma cholesterol (mmol/l).
VLDL cholesterol Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis). Plasma very low-density lipoproteins (mmol/l).
LDL cholesterol Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis). Plasma low-density lipoprotein (LDL) (mmol/l).
HDL cholesterol Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis). Plasma high-density lipoprotein (HDL) (mmol/l).
Malondialdehyde Results from samples taken on day 15 and adjusted for results from day 1. Malondialdehyde measured in blood or morningurine samples as a marker of oxidative stress.
Protein carbonyls Results from samples taken on day 15 and adjusted for results from day 1. Protein carbonyls measured in blood or morningurine samples as a marker of protein oxidation.
Glycated hemoglobin (HbA1c) Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis). HbA1c (IFCC, mmol/mol) measured in whole blood. Estimated average glucose values (mmol/l) are also calculated automatically from HbA1c by our laboratory.
Changes in the gut microbiome 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. Characterization of the gut microbiome using molecular biology methods such as 16s rRNA sequencing.
Characterization of the metabolic activity of the gut microbiota 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. Targetted and untargetted liquid-chromatography mass-spectrometry-based metabolomics. Targetted analyses aim to quantify indole-3-propionic acid, other bacterial- and host metabolites of tryptophan as well as short-chain fatty acids.
Bacterial polysaccharides Results from samples taken on day 15 and adjusted for results from day 1. Endotoxin, capsular polysaccharides or other bacterial polysaccharides measured in blood samples as biomarker of bacterial translocation across the intestinal epithelium.
Pre-haptoglobin 2 Results from samples taken on day 15 and adjusted for results from day 1. Measurement of pre-haptoglobin 2 in blood samples as a biomarker of intestinal permeability.
Intestinal fatty acid binding protein Results from samples taken on day 15 and adjusted for results from day 1. Measurements of intestinal fatty acid binding protein in blood samples as a biomarker of enterocyte damage.
Citrulline Results from samples taken on day 15 and adjusted for results from day 1. Measurement of citrulline in blood samples as a biomarker of intestinal function.
Calprotectin Results from samples taken on day 15 and adjusted for results from day 1. Calprotectin measured in fecal samples as a biomarker of intestinal inflammation.
Neopterin Results from samples taken on day 15 and adjusted for results from day 1. Neopterin measured in morningurine samples as a biomarker of systemic inflammation.
suPAR Results from samples taken on day 15 and adjusted for results from day 1. Soluble urokinase plasminogen activator receptor (suPAR) measured in blood samples.
Microvesicles Results from samples taken on day 15 and adjusted for results from day 1. Flow cytometric analyses of microvesicles/ microparticles in platelet-free plasma as biomarker of systemic inflammation.
Endothelial progenitor cells Results from samples taken on day 15 and adjusted for results from day 1. Flow cytometric analyses of endothelial progenitor cells measured in platelet-free plasma as biomarker of systemic inflammation
Trial Locations
- Locations (1)
Optic Neuritis Clinic, Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet-Glostrup
🇩🇰Glostrup, Denmark
Optic Neuritis Clinic, Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet-Glostrup🇩🇰Glostrup, Denmark