Indole-3-PROpionic Acid Clinical Trials - a Pilot Study (iPROACT-pilot)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 79
- 试验地点
- 1
- 主要终点
- Regulatory T cells (first primary outcome)
研究概览
简要总结
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.
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 bottle is named with a unique number (1-96) and no other identifier. Capsule bottles have already been randomized by the external party using block randomization with random block sizes of 4 or 8. Study participants receive the next available capsule bottle 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 as well as the identity of the groups. This is a prerequisite for performance of statistical analyses, as the primary analysis is defined as the comparison between the group with the highest treatment dose and placebo.
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
- •Pregnant or lactating women or birth within the last five months
- •Use of medicine that requires prescription
研究组 & 干预措施
Placebo
Placebo
干预措施: Placebo (Dietary Supplement)
500 mg IPA
500 mg indole-3-propionic acid
干预措施: Indole-3-propionic acid (Dietary Supplement)
120 mg IPA
120 mg indole-3-propionic acid
干预措施: Indole-3-propionic acid (Dietary Supplement)
50 mg IPA
50 mg indole-3-propionic acid
干预措施: Indole-3-propionic acid (Dietary Supplement)
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 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)
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 dosis).
Brain-derived neurotrophic factor measured in plasma samples using ELISA or mesoscale.
次要结局
- 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).)
- 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).)
- Triglycerides(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(Results from fasting blood samples taken on day 15 and adjusted for results from day 1 (fasting just before first supplement/placebo dosis).)
- 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).)
- 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).)
- Isoprostane-F2-alpha(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 dosis).)
- 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).)
- 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).)
- 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).)
- 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 dosis).)
- 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
Professor, Clinical Consultant, DMSc, MD
Glostrup University Hospital, Copenhagen