Indole-3-PROpionic Acid Clinical Trials - a Pilot Study Part 2
ConditionHealthy
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-65
SponsorGlostrup University Hospital, Copenhagen
About this trial
The goal of this trial is to investigate the biological effects of oral supplementation with indole-3-propionic acid (IPA) taken twice daily in healthy adults. The main scientific questions are:
* Does supplementation with IPA increase the abundance of 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?
Participants will:
* Take capsules to achieve a total daily dose of 1000 mg of IPA or placebo: 500 mg every morning and 500 mg every evening for 14 days. * Visit the clinic at the beginning (day 1) and at the end (day 15) of the supplementation period to deliver blood, urine and fecal samples, have simple measurements performed, fulfil questionnaires and report any side effects.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Healthy women and men ≥18 and ≤65 years of age
Deemed mentally and physically able to participate
Disqualifiers
Diagnosis of gut-, heart-, liver-, kidney or immune-related disorders
Use of antibiotics within the last month
Pregnancy, lactation or childbirth within the last five months
Use of prescription medication
Trial design
Design model
Parallel
Treatments tested in this trial
Indole-3-propionic acid (IPA)
Dietary supplementTwo capsules are taken every morning and two capsules are taken every evening for 14 consecutive days. Active capsules are taken orally and contain 250 mg of IPA each.
Placebo
Dietary supplementTwo capsules are taken every morning and two capsules are taken every evening for 14 consecutive days. Placebo capsules are taken orally and contain maltodextrin.
Treatment groups
32 Participants
are divided into 2 treatment groupsGroup A: PlaceboPlacebo comparator 1 intervention
Group B: Indole-3-propionic acid (IPA)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Regulatory T cells (first primary outcome)
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.
Time frame
Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose).2
Brain-derived neurotrophic factor (second primary outcome)
Brain-derived neurotrophic factor measured in platelet-free plasma samples using ELISA or mesoscale.
Time frame
Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose).Secondary outcomes
1
Th1/Th2 ratio in PBMCs
Th1/Th2 ratio calculated from T cell profiling of freshly isolated peripheral blood mononuclear cells (PBMCs) using a Symphony A3 flowcytometer. Th1 cells are defined as the CXCR3+CCR4-CCR6-CCR10- non-Treg population and expressed as a percentage of single, live CD3+CD4+CD8-CD45RA- lymphocytes. Th2 cells are defined as the CXCR3-CCR4+CCR6-CCR10- non-Treg population and expressed as a percentage of single, live CD3+CD4+CD8-CD45RA- lymphocytes. Panel antigens: FVS780, CD3, CD4, CD8, CD45RA, CCR7, CXCR3, CCR6, CCR4, CCR10, CD25, CD127, FoxP3.
Time frame
Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose).2
Th17/mTreg ratio in PBMCs
Th17/mTreg ratio calculated from T cell profiling of freshly isolated peripheral blood mononuclear cells (PBMCs) using a Symphony A3 flowcytometer. Th17 cells are defined as the CXCR3-CCR4+CCR6+CCR10- non-Treg population and expressed as a percentage of single, live CD3+CD4+CD8-CD45RA- lymphocytes. mTreg (memory Tregs) are defined as the FoxP3+CD25+CD127-CD45RA- population and expressed as a percentage of single, live CD3+CD4+CD8-CD45RA- lymphocytes Panel antigens: FVS780, CD3, CD4, CD8, CD45RA, CCR7, CXCR3, CCR6, CCR4, CCR10, CD25, CD127, FoxP3.
Time frame
Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose).3
Th17.1 cells in PBMCs
Th17.1 cells in freshly isolated peripheral blood mononuclear cells (PBMCs) characterized using a Symphony A3 flowcytometer. Th17.1 cells are defined as the CXCR3+CCR4-CCR6+CCR10- non-Treg population and expressed as a percentage of single, live CD3+CD4+CD8-CD45RA- lymphocytes Panel antigens: FVS780, CD3, CD4, CD8, CD45RA, CCR7, CXCR3, CCR6, CCR4, CCR10, CD25, CD127, FoxP3.
Time frame
Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose).4
CRP
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.
Time frame
Results from blood samples taken on day 15 (just before last supplement/placebo dose) and adjusted for results from day 1 (just before first supplement/placebo dose).Other outcomes
1
Gastrointestinal comfort
Self-reported (questionnaire) gastrointestinal symptoms of bloating, pain, rumbling, flatulence, constipation, hard stools and diarrhea evaluated using a visual analogue scale as well as a question on the frequency of defecation.
Time frame
Gastrointestinal symptoms are assessed on day 1 and day 15.2
Gastrointestinal transit time
Measurement of transit time through the digestive system using a so-called maize test. Participants consume 100 grams of sweet maize in the morning between 5.30-10.00 while still in a fasting state. The exact date and time of consumption is registered and so is the exact date and time when maize is observed for the first time in feces. Transit time is expressed as the difference between the ingestion and fecal excretion timepoints in hours.
Time frame
The maize test is performed at baseline (maize is ingested five days before visit 1) and repeated on day 10 (five days before visit 2).3
Stool consistency
Classification of stool consistency using the Bristol Stool Chart. Numerical scale ranging from 1 (separate hard lumps) to 7 (liquid consistency with no solid pieces) with one-unit increments.
Time frame
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)).4
Fecal pH
pH of collected fecal samples
Time frame
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).Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Glostrup University Hospital, Copenhagen
Lead sponsor
University of Copenhagen
Collaborator
University of Southampton
Collaborator
Source ClinicalTrials.gov