Indole-3-PROpionic Acid Clinical Trials - a Pilot Study Part 2 (iPROACT-pilot2)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Regulatory T cells (first primary outcome)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy women and men ≥18 and ≤65 years of age
- •Deemed mentally and physically able to participate
排除标准
- •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
结局指标
主要结局
Regulatory T cells (first primary outcome)
时间窗: Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose).
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)
时间窗: 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 measured in platelet-free plasma samples using ELISA or mesoscale.
次要结局
- Th1/Th2 ratio in PBMCs(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(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(Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose).)
- CRP(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(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(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(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(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(Results from samples taken on day 15 and adjusted for results from day 1.)
- 8-oxo-dG(Results from samples taken on day 15 and adjusted for results from day 1.)
- 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.)
- Total cholesterol(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(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(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(Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dose).)
- Malondialdehyde(Results from samples taken on day 15 and adjusted for results from day 1.)
- Protein carbonyls(Results from samples taken on day 15 and adjusted for results from day 1.)
- 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 dose).)
- T cell profiling(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(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(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(Results from samples taken on day 15 and adjusted for results from day 1.)
- Pre-haptoglobin 2(Results from samples taken on day 15 and adjusted for results from day 1.)
- Intestinal fatty acid binding protein(Results from samples taken on day 15 and adjusted for results from day 1.)
- Citrulline(Results from samples taken on day 15 and adjusted for results from day 1.)
- Calprotectin(Results from samples taken on day 15 and adjusted for results from day 1.)
- Neopterin(Results from samples taken on day 15 and adjusted for results from day 1.)
- suPAR(Results from samples taken on day 15 and adjusted for results from day 1.)
- Microvesicles(Results from samples taken on day 15 and adjusted for results from day 1.)
- Endothelial progenitor cells(Results from samples taken on day 15 and adjusted for results from day 1.)
研究者
Jette Lautrup Frederiksen
Prof, DMSc, MD
Glostrup University Hospital, Copenhagen