Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of Copenhagen | OTHER |
| University of Southampton | OTHER |
Not provided
Not provided
Not provided
Not provided
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:
Participants will:
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo |
|
| Indole-3-propionic acid (IPA) | Experimental | IPA: total daily dose of 1000 mg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Indole-3-propionic acid (IPA) | Dietary Supplement | Two 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| Brain-derived neurotrophic factor (second primary outcome) | Brain-derived neurotrophic factor measured in platelet-free plasma samples using ELISA or mesoscale. | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Gastrointestinal symptoms are assessed on day 1 and day 15. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Moschoula Passali, MSc, PhD | Contact | +45 38633467 | moschoula.passali@regionh.dk |
| Name | Affiliation | Role |
|---|---|---|
| Jette Frederiksen, Prof, MD | Copenhagen University Hospital, Rigshospitalet-Glostrup | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Optic Neuritis Clinic, Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet-Glostrup | Recruiting | Glostrup Municipality | 2600 | Denmark |
Individual participant data that underlie the results reported in published articles, after deidentification (text, tables, figures, and appendices).
Beginning 3 months and ending 5 years following publication of the article they are presented in.
Researchers who provide a methodologically sound proposal can access the IPD to achieve the aims of the approved proposal. Proposals should be directed to jette.lautrup.battistini@regionh.dk. To gain access, data requestors will need to sign a data access agreement. Data and explanatory files will be made available at a third party website.
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 16, 2025 | Jul 29, 2025 | SAP_000.pdf |
Not provided
Not provided
Not provided
Not provided
Randomization is performed by external party. Each capsule container is labelled with a unique number (101-160) and no other identifier. Capsule containers have already been randomized by the external party using block randomization with random block sizes of 2 or 4. Study participants receive the next available capsule container based on their order of recruitment. This way, everyone involved in the study is fully blinded and it is also impossible to guess which participants belong to the same group. Only after all study participants have been recruited and the collected data have been cleaned and quality checked, are the researchers performing the statistical analyses informed about which participants belong to the same group.
| Placebo | Dietary Supplement | Two capsules are taken every morning and two capsules are taken every evening for 14 consecutive days. Placebo capsules are taken orally and contain maltodextrin. |
|
| Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| 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. | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| 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. | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| 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. | 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). |
| Triglycerides | Plasma triglycerides (mmol/l). | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| non-HDL cholesterol | Non-HDL cholesterol calculated as total cholesterol minus HDL cholesterol (mmol/l) | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| C-peptide | Proinsulin C-peptide (pmol/l) measured in plasma. | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| Fasting glucose | 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. | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| F2-isoprostanes | F2-isoprostanes with a specific focus on 8-iso-prostaglandin F2α measured in blood or morningurine samples as a marker of lipid oxidation. | Results from samples taken on day 15 and adjusted for results from day 1. |
| 8-oxo-dG | 8-oxo-dG (8-Oxo-2'-deoxyguanosine) measured in blood or morningurine samples as a marker of DNA-related stress damage. | Results from samples taken on day 15 and adjusted for results from day 1. |
| Serum metabolomics | 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. | 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. |
| Total cholesterol | Plasma cholesterol (mmol/l). | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| VLDL cholesterol | Plasma very low-density lipoproteins (mmol/l). | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| LDL cholesterol | Plasma low-density lipoprotein (LDL) (mmol/l). | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| HDL cholesterol | Plasma high-density lipoprotein (HDL) (mmol/l). | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| Malondialdehyde | Malondialdehyde measured in blood or morningurine samples as a marker of oxidative stress. | Results from samples taken on day 15 and adjusted for results from day 1. |
| Protein carbonyls | Protein carbonyls measured in blood or morningurine samples as a marker of protein oxidation. | Results from samples taken on day 15 and adjusted for results from day 1. |
| Glycated hemoglobin (HbA1c) | HbA1c (IFCC, mmol/mol) measured in whole blood. Estimated average glucose values (mmol/l) are also calculated automatically from HbA1c by our laboratory. | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| T cell profiling | Targetted and untargetted T cell profiling of freshly isolated peripheral blood mononuclear cells (PBMCs) using a Symphony A3 flowcytometer. Panel antigens: FVS780, CD3, CD4, CD8, CD45RA, CCR7, CXCR3, CCR6, CCR4, CCR10, CD25, CD127, FoxP3. Target populations: Naïve: CD45RA+CCR7+, Central memory: CD45RA-CCR7+, Effector memory: CD45RA-CCR7-, TEMRA: CD45RA+CCR7-, 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+, as well as expression of chemokine receptors on cytotoxic T cells and regulatory T cells. An untargetted approach may be employed to allow for unbiased identification of changes in novel, yet uncharacterized populations. | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| Changes in the gut microbiome | Characterization of the gut microbiome using molecular biology methods such as 16s rRNA sequencing. | 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 metabolic activity of the gut microbiota | 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. | 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. |
| Bacterial polysaccharides | Endotoxin, capsular polysaccharides or other bacterial polysaccharides measured in blood samples as biomarker of bacterial translocation across the intestinal epithelium. | Results from samples taken on day 15 and adjusted for results from day 1. |
| Pre-haptoglobin 2 | Measurement of pre-haptoglobin 2 in blood samples as a biomarker of intestinal permeability. | Results from samples taken on day 15 and adjusted for results from day 1. |
| Intestinal fatty acid binding protein | Measurements of intestinal fatty acid binding protein in blood samples as a biomarker of enterocyte damage. | Results from samples taken on day 15 and adjusted for results from day 1. |
| Citrulline | Measurement of citrulline in blood samples as a biomarker of intestinal function. | Results from samples taken on day 15 and adjusted for results from day 1. |
| Calprotectin | Calprotectin measured in fecal samples as a biomarker of intestinal inflammation. | Results from samples taken on day 15 and adjusted for results from day 1. |
| Neopterin | Neopterin measured in morningurine samples as a biomarker of systemic inflammation. | Results from samples taken on day 15 and adjusted for results from day 1. |
| suPAR | Soluble urokinase plasminogen activator receptor (suPAR) measured in blood samples. | Results from samples taken on day 15 and adjusted for results from day 1. |
| Microvesicles | Flow cytometric analyses of microvesicles/ microparticles in platelet-free plasma as biomarker of systemic inflammation. | Results from samples taken on day 15 and adjusted for results from day 1. |
| Endothelial progenitor cells | Flow cytometric analyses of endothelial progenitor cells measured in platelet-free plasma as biomarker of systemic inflammation | Results from samples taken on day 15 and adjusted for results from day 1. |
| 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. |
| 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). |
| 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. | 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)). |
| Fecal pH | pH of collected fecal samples | 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). |
| Antibody-coating of bacteria | Characterization of IgA, IgG and IgM-coating of bacteria from fecal samples using bacterial flow cytometry. | 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). |
| Immunoglobulin G | Plasma immunoglobulin G (g/l) | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (just before first supplement/placebo dose). |
| Immunoglobulin A | Plasma immunoglobulin A (g/l) | 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). |
| Leucocyte counts | Total leucocytes as well as basophils, eosinophils, lymphocytes, monocytes, neutrophils as well as the joint group of metamyelo-, myelo- and promyelocytes. All counted in whole blood samples (10^9/l). | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (just before first supplement/placebo dose). |
| Hemoglobin | Hemoglobin measured in whole blood (mmol/l). | 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). |
| Alanine transaminase | Plasma alanine transaminase (ALT, U/l) as a biomarker of liver function. | Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose). |
| Alkaline phosphatase | Alkaline phosphatase (U/l) as a biomarker of liver function. | 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). |
| Aspartate aminotransferase | Aspartate aminotransferase also known as aspartate transaminase measured in plasma (U/l) as a biomarker of liver damage. | 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). |
| Bilirubin | Bilirubins measured in plasma (µmol/L) as a biomarker of liver function. | 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). |
| Coagulation factors II + VII + X | Coagulation factors II + VII + X (INR: International Normalized Ratio) measured in plasma as a biomarker of liver function. | 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). |
| Lactate dehydrogenase (LDH) | Lactate dehydrogenase measured in plasma (U/l). | 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). |
| Creatinine | Plasma creatinine (µmol/L) as a biomarker of kidney function. | 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) |
| eGFR | Estimated glomerular filtration rate (eGFR/ 1,73m² (ml/min)) as a biomarker of kidney function. | 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). |
| Albumin | Albumin measured in plasma (g/l). | 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). |
| 25-OH-vitamin D | Plasma 25-OH-vitamin D (D3+D2) (nmol/L) | 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). |
| TSH | Thyroid-stimulating hormone (TSH) measured in plasma (mU/L) | 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). |
| Blood pressure | Blood pressure (mm Hg) defined as the lowest value obtained across three measurements. | Measured on day 1 and then again on day 15 |
|