Cardiovascular Diseases (CVD), Dietary Fiber, Gastrointestinal Microbiome, Insulin Resistance, Inulin, Microbiota, Muscle, Skeletal, Obesity & Overweight, Perimenopausal Women, Prebiotics, Vascular Health, Women Health
Conditions
Keywords
Perimenopause, Nutrition, Menopause transition, Overweight, Obesity, Cardiometabolic Health, Vascular function, Randomized Controlled Trial, Gut microbiome, Vaginal microbiome, Supplements, Inulin, Vascular Health
Brief summary
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_SUPPLEMENTInulin
10g per day for 2 weeks
DIETARY_SUPPLEMENTMaltodextrin (Placebo)
10g per day for 2 weeks
Sponsors
George Washington University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Intervention model description
Blinded Cross-Over Randomized Controlled Trial
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Gut Microbiome Composition | Baseline, end of each 2-week intervention period (inulin and placebo), and after washout period (2-4 weeks). | Change in gut microbiome composition, assessed by shotgun metagenomic sequencing, comparing inulin versus placebo in a randomized crossover design. |
| Change in Gut Microbiome Functional Capacity | Baseline, end of each 2-week intervention period (inulin and placebo), and after washout period (2-4 weeks). | Change in gut microbiome functional capacity, including biosynthetic gene clusters (BGCs) and estrobolome-related microbial pathways, assessed by shotgun metagenomic sequencing, comparing inulin versus placebo in a randomized crossover design. |
| Change in Vaginal Microbiome Composition | Baseline, end of each 2-week intervention period (inulin and placebo), and after washout period (2-4 weeks). | Change in vaginal microbiome composition, assessed by shotgun metagenomic sequencing, comparing inulin versus placebo in a randomized crossover design. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vascular Function | 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). | Change in vascular function, assessed by pulse-wave velocity (PWV), comparing inulin versus placebo in a randomized crossover design. |
| Metabolic Flexibility | 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). | Change in metabolic flexibility, assessed as the change in respiratory exchange ratio (RER) from the fasted resting state to the postprandial period following a standardized high-fat mixed meal, measured continuously via indirect calorimetry, comparing inulin versus placebo in a randomized crossover design. |
| Skeletal muscle mitochondrial oxidative capacity | 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) | Change in skeletal muscle mitochondrial oxidative capacity in the gastrocnemius muscle, comparing inulin versus placebo in a randomized crossover design. Muscle oxidative capacity will be assessed using near-infrared spectroscopy (NIRS). |
Countries
United States
Contacts
CONTACTCarmen Ortega-Santos, PhD, RD
Outcome results
None listed