Prebiotic Inulin for Late-Reproductive Individuals

Official title

A Placebo Randomized Cross-Over Controlled Trial of Inulin Supplementation to Improve Cardiometabolic, Gut, and Vaginal Microbiome in Perimenopausal Women

Overview

This study aims to evaluate the effects of 2 weeks of inulin supplementation in perimenopausal women with overweight or obesity. The primary questions this study seeks to answer are: 1. Does 2 weeks of inulin supplementation alter the gut and vaginal estrobolome compared with placebo? 2. Does 2 weeks of inulin supplementation affect cardiovascular health compared with placebo? 3. Does 2 weeks of inulin supplementation affect skeletal muscle health compared with placebo? Researchers will compare inulin with a placebo (a similar-looking supplement that does not contain inulin) to determine whether inulin influences gut and vaginal microbial function, cardiovascular health, and skeletal muscle health during the perimenopausal transition. Participants will: * Take either inulin or a placebo for 2 weeks, followed by a 2- to 4-week washout period, and then switch to the other supplement for an additional 2 weeks. * Attend 8 study visits over approximately 12 to 16 weeks for assessments and sample collection. * Complete weekly phone calls to monitor symptoms, supplement adherence, and dietary intake. * Wear a Fitbit device throughout the study to monitor physical activity.

Detailed description

This proposal presents a proof-of-concept study of the Prebiotic Inulin for Late Reproductive Individuals (PILI) intervention, a prebiotic fiber supplementation among women with perimenopause and overweight or obesity.

More specifically, the PILI intervention integrates multi-omics, physiological, and cardiometabolic assessments to examine the effects of inulin supplementation on overall health during the menopausal transition. Outcomes include changes in the gut and vaginal microbiome and their functional activity, gut-derived metabolites, vascular health, metabolic flexibility, skeletal muscle oxidative capacity, body composition, physical activity, sleep, dietary intake, and other cardiometabolic health markers. The target age range for this intervention is 40-55 years, reflecting the perimenopausal stage of life. Participants must also have overweight or obesity.

Participants will be randomly assigned to receive both the study intervention, inulin, and placebo, in a blind crossover design. Each participant will complete two intervention periods, separated by a washout period, allowing every participant to serve as her own control. Throughout the study, participants will consume the assigned supplement daily and attend scheduled in-person research visits before and after each intervention period.

At these visits, the research team will collect biological samples, including blood, stool, and vaginal swabs, and perform a comprehensive series of clinical assessments. These assessments include body composition, vascular health, metabolic flexibility, skeletal muscle oxidative capacity using near-infrared spectroscopy, physical function, and cardiometabolic testing. Participants will also complete questionnaires related to dietary intake, physical activity, sleep, menopausal symptoms, and quality of life, while wearing a Fitbit device to objectively monitor physical activity and sleep throughout the study.

The PILI study team will evaluate the feasibility of the intervention by assessing recruitment, retention, adherence to supplement consumption and study procedures, participant acceptability and tolerability, and completion of biological sample collection and clinical assessments. Preliminary changes in microbiome composition and function, microbial metabolites, and cardiometabolic health outcomes will also be evaluated to generate data that will inform the design of a future larger clinical trial.

This research has the potential to advance understanding of how prebiotic supplementation influences the gut-muscle-metabolism axis during the menopausal transition and to identify a safe, low-cost nutritional strategy to improve cardiometabolic health among perimenopausal women.

Interventions

• Dietary supplement Inulin
  10g per day for 2 weeks
• Dietary supplement Maltodextrin (Placebo)
  10g per day for 2 weeks

Primary outcome measures

• Change in Gut Microbiome Composition [Time frame: Baseline, end of each 2-week intervention period (inulin and placebo), and after washout period (2-4 weeks).]
• Change in Gut Microbiome Functional Capacity [Time frame: Baseline, end of each 2-week intervention period (inulin and placebo), and after washout period (2-4 weeks).]
• Change in Vaginal Microbiome Composition [Time frame: Baseline, end of each 2-week intervention period (inulin and placebo), and after washout period (2-4 weeks).]

Secondary outcome measures (3)

• Vascular Function [Time frame: Baseline and end of each 2-week intervention period (inulin and placebo), with assessments conducted during each intervention period following the washout phase (2-4 weeks).]
• Metabolic Flexibility [Time frame: Baseline and end of each 2-week intervention period (inulin and placebo), with assessments conducted during each intervention period following the washout phase (2-4 weeks).]
• Skeletal muscle mitochondrial oxidative capacity [Time frame: Baseline and end of each 2-week intervention period (inulin and placebo), with assessments conducted during each intervention period following the washout phase (2-4 weeks)]

Eligibility criteria

Inclusion criteria

• Body mass index: 25 - 40 kg/m2;
• Menstrual cycle irregularity (cycle length outside 21 - 35 days or variation > 7 days) or/and ≥ 2 skipped cycles and interval of ≥ 60 days of amenorrhea; with or without hot flashes or/and night sweats;
• Weight stable within the last 3 months (body weight fluctuations within the 5% of their habitual body weight);
• Spending ≥ 6 hours sitting;
• < 150 minutes per week (50 minutes per day, 3 days per week OR 30 minutes per day, 5 days per week) of moderate to vigorous structured physical activity (i.e., planned intentional physical activity, not incidental movement).

Exclusion criteria

• Recent antibiotic use oral or vaginal (≥ 6months);
• Diagnosed with any chronic disease (e.g., any gastrointestinal condition like IBD, type 2 diabetes, or cancer);
• Prescription of hormone replacement therapy, hormonal contraceptives, probiotics, GLP-1 medications, or weight loss medications
• Smoking;
• Recent blood donation (within the past 8-12 weeks);
• Significant weight changes (≥5%) in the last 4 weeks;
• Use of dietary supplements (unless discontinued 4 weeks prior);
• Participants taking long-term, stable medications for chronic conditions such as hypertension or hyperlipidemia will not be excluded if their medication regimen has been unchanged for at least 2 years, as these treatments are part of their usual health status. Recent medication changes (within the past 6 months), initiation of new prescriptions, or use of medications known to affect metabolic, vascular, vaginal, hormonal, or gastrointestinal function will result in exclusion.
• Fructose intolerance.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Prevention

Study locations

United States · 1 center

• Milken Institute School of Public Health — Washington D.C.

Publications

• Huang F, Cao Y, Liang J, Tang R, Wu S, Zhang P, Chen R. The influence of the gut microbiome on ovarian aging. Gut Microbes. 2024 Jan-Dec;16(1):2295394. doi: 10.1080/19490976.2023.2295394. Epub 2024 Jan 3. PMID 38170622
• Wang H, Shi F, Zheng L, Zhou W, Mi B, Wu S, Feng X. Gut microbiota has the potential to improve health of menopausal women by regulating estrogen. Front Endocrinol (Lausanne). 2025 Jun 9;16:1562332. doi: 10.3389/fendo.2025.1562332. eCollection 2025. PMID 40551890
• Houghton MJ, Kerimi A, Mouly V, Tumova S, Williamson G. Gut microbiome catabolites as novel modulators of muscle cell glucose metabolism. FASEB J. 2019 Feb;33(2):1887-1898. doi: 10.1096/fj.201801209R. Epub 2018 Sep 5. PMID 30183376
• Cross TL, Simpson AMR, Lin CY, Hottmann NM, Bhatt AP, Pellock SJ, Nelson ER, Loman BR, Wallig MA, Vivas EI, Suchodolski J, Redinbo MR, Rey FE, Swanson KS. Gut microbiome responds to alteration in female sex hormone status and exacerbates metabolic dysfunction. Gut Microbes. 2024 Jan-Dec;16(1):2295429. doi: 10.1080/19490976.2023.2295429. Epub 2023 Dec 28. PMID 38153260
• Cavallari JF, Schertzer JD. Intestinal Microbiota Contributes to Energy Balance, Metabolic Inflammation, and Insulin Resistance in Obesity. J Obes Metab Syndr. 2017 Sep;26(3):161-171. doi: 10.7570/jomes.2017.26.3.161. Epub 2017 Sep 30. PMID 31089513
• Cabre HE, Gould LM, Gordon AN, Giuliani-Dewig HK, Moore SR, Ryan ED, Smith-Ryan AE. Differences in strength, leg lean mass, and lifestyle factors between premenopausal and perimenopausal women. Clin Physiol Funct Imaging. 2022 Nov;42(6):460-464. doi: 10.1111/cpf.12771. Epub 2022 Jul 26. PMID 35762156
• Gould LM, Gordon AN, Cabre HE, Hoyle AT, Ryan ED, Hackney AC, Smith-Ryan AE. Metabolic effects of menopause: a cross-sectional characterization of body composition and exercise metabolism. Menopause. 2022 Feb 28;29(4):377-389. doi: 10.1097/GME.0000000000001932. PMID 35231009
• Le Bastard Q, Chapelet G, Javaudin F, Lepelletier D, Batard E, Montassier E. The effects of inulin on gut microbial composition: a systematic review of evidence from human studies. Eur J Clin Microbiol Infect Dis. 2020 Mar;39(3):403-413. doi: 10.1007/s10096-019-03721-w. Epub 2019 Nov 9. PMID 31707507

Identifiers

NCT: NCT07724522 · NCR267325 · 05RIA112025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗