Effects of a 6-months Fiber- and Polyphenol-rich Diet on Brain Inflammatory Processes in Perimenopausal Women Living With Overweight or Obesity

NCT07501377 | Recruiting

• 1 other identifier: NRO-286
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

People living with obesity have a higher risk of late-life cognitive decline and developing dementia. In women, the risk of cognitive decline may further raise during the menopausal transition, a period of substantial hormonal and metabolic changes. Recent studies suggest that a healthy diet could help to prevent neurocognitive disorders by reducing inflammatory processes in the body and brain. Emerging evidence further indicates that the gut-brain axis and the intestinal microbiome play a crucial role in mediating this effect, through metabolic, immune, neuronal and vascular routes. Modifying the gut microbiota may thus counteract the heightened systemic inflammation seen in obesity and during menopausal transition to eventually benefit brain health. Specifically, plant-based nutirents, such as fibre and polyphenols, have microbiome-changing, anti-inflammatory and neuroprotective properties that may slow brain aging and neuro-inflammation. However, evidence from human interventional studies and knowledge on the underlying mechanisms remain scarce. This randomized controlled trial will therefore test whether altering gut bacteria through six months of daily intake of a personalized "polybiotic" dietary formula, compared to placebo, improves markers of brain health in women during the perimenopausal transition that are living with overweight or obesity. We plan to enroll 120 women aged 35-60 with overweight/obesity and elevated inflammatory blood markers, randomized to: intervention (7.5 or 15 g inulin, plus 200 mg resveratrol and 320 mg quercetin per day in powder form with main meals) or control (isocaloric maltodextrin). Exclusions include type 1 diabetes, current psychiatric/gastrointestinal disorders, and magentic resonance imaging (MRI) contraindications. Before and after 26 weeks, participants will undergo brain MRI to assess inflammation-related brain markers, neuropsychological testing, anthropometric measurements, they will fill in a set of questionnaires and donate stool and blood. Gut bacteria will be profiled by next-generation sequencing; metabolites will be measured in blood and stool. The primary outcome is a proxy of neuroinflammation in the white matter assessed using diffusion-weighted MRI. Secondary analyses will examine blood-brain-barrier permeability and other functional and structural MRI measures, including MR spectoscropy. Mechanistic links among changes in inflammatory markers, microbiota composition, and short-chain fatty acids will be explored using path and network models. This study may help to develop novel prevention and treatment strategies to mitigate obesity-related cognitive decline via the gut-brain axis.

Conditions

Overweight and/or Obesity; Perimenopausal Women

Keywords

neuroinflammation; obesity; overweight; menopausal transition; gut-brain axis; diet; diffusion-weighted MRI; cognitive decline; brain aging; MR spectroscopy; prevention; open science

Outcome Measures

Primary Outcomes (1)

• Free water fraction averaged across the white matter skeleton

  Free water (measured using multi-shell diffusion-weighted MRI at 3 Tesla) reflects extra-cellular water which can be considered an indicator of tissue edema and impaired blood brain barrier

  6 months

Secondary Outcomes (5)

• Average grey matter kw from motion-compensated diffusion-weighted arterial spin labeling (ASL)

  6 months

• Apparent diffusion coefficient of metabolites in the thalamus from diffusion-weighted MR spectoscropy

  6 months

• Hypothalamic and hippocampal microstructure

  6 months

• Episodic memory

  6 months

• Microbial Composition

  6 months

Other Outcomes (13)

• soma signal fraction in thalamus and hippocampus derived from multi-shell diffusion-weighted MRI

  6 months

• Pattern separation

  6 months

• Executive function

  6 months

Study Arms (2)

Personalized intervention arm

EXPERIMENTAL

Daily intake of 7.5g or 15g of inulin + 200mg resveratrol + 320mg quercetin in a powder formula with main meals in the first half of day, over the course of 6 months. The lower or higher inulin dosage will be assigned depending on the participants' microbiome composition at baseline.

Dietary Supplement: Polybiotic dietary intervention

Placebo arm

PLACEBO COMPARATOR

Daily intake of equicaloric maltodextrin

Dietary Supplement: Placebo

Interventions

Polybiotic dietary intervention DIETARY_SUPPLEMENT

7.5g or 15g of inulin + 200mg resveratrol + 320mg quercetin in a powder formula

Personalized intervention arm

Placebo DIETARY_SUPPLEMENT

Equicaloric maltodextrin in powder form

Placebo arm

Eligibility Criteria

• Age: 35 Years - 60 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• STRAW+10 -1 or -2
• BMI \> 25 or WHR \>= 0.85
• hsCRP \> 1 mg/l
• no MRI contra-indication
• written informed consent

You may not qualify if:

• occurrence of a clinically relevant psychiatric disease in the last 12 months (e.g., depression, substance abuse, eating disorder, schizophrenia)
• type 1 diabetes
• previous bariatric/gastric surgery
• pregnancy or breastfeeding woman
• severe untreated disease, cancer treatment last 12 months, any chronic gastric tract disease (IBS, Morbus Crohn, Heliobacter pylori Infection etc.) or any chronic inflammatory disease
• Polycystic ovary syndrome, total ovarectomy
• Intake of antibiotics in past 3 months, intake of inulin (\>5g/day) or polyphenol supplementation (\>50mg/day) in past 3 months

Sponsors & Collaborators

• Max Planck Institute for Human Cognitive and Brain Sciences: lead

Study Sites (1)

Max Planck Institute for Human Cognitive and Brain Sciences

Leipzig, Saxony, 04103, Germany

RECRUITING

MeSH Terms

Conditions

Neuroinflammatory Diseases; Obesity; Overweight; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Veronica Witte, PhD

  University of Leipzig Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2026
• First Posted: March 30, 2026
• Study Start: March 19, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

DE (1)