Aging Resilience Through Microbiota Optimization and Regulation

NCT06649981 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: WL-DR-GJDynamic resilience programme
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

Sarcopenia, characterized by the progressive loss of muscle mass and strength in older adults, is a key factor in health deterioration. It affects 15% of people between 65 and 80 years old and over 50% of those over 80, compromising autonomy and increasing the risk of diseases. Sarcopenia not only impacts muscle function but also bone health, mobility, and is associated with cardiometabolic diseases and cognitive decline. It has been proposed that changes in the gut microbiota in aging individuals, known as gut dysbiosis, contribute to sarcopenia. Species diversity decreases, and bacterial representation is altered, which could impair muscle function through various pathways, such as mitochondrial dysfunction, chronic inflammation, and disruption of protein synthesis. Muscle function loss is strongly associated with cognitive and metabolic impairment in older adults. Recently, it has been demonstrated that fecal microbiota transplantation (FMT) is an effective procedure for modulating gut microbiota and has proven highly effective in managing cases of Clostridium difficile-associated chronic diarrhea. The main objective of this project is to carry out FMT from young, physically active donors to a cohort of older adults to evaluate its effect on muscle, cognitive, and metabolic function. Why donors who exercise? There is growing evidence that gut microbiota diversity is increased in young, physically active individuals. The FMT is planned to be administered through lyophilized microbiota capsules. By restoring microbial diversity, it is expected to improve the quality and function of skeletal muscles, leading to greater cognitive and metabolic resilience. This project has great potential to develop an innovative approach for treating highly debilitating diseases that affect older adults, based on the lyophilization and encapsulation of gut microbiota from young, trained donors, which can be easily stored in a conventional freezer. Due to the high percentage of older adults worldwide and the high prevalence of sarcopenia within this age group, the aim of the project is to address a significant public health issue with a large target population eager for options to promote muscle health, functional autonomy, as well as cognitive and metabolic well-being.

Conditions

Resilience; Cognitive Function and Well-Being; Muscle Function, Handgrip Strength Test; Insulin Sensitivity

Keywords

FMT; Resilience; gut microbiota; aging; cognition; muscle function; metabolic function

Outcome Measures

Primary Outcomes (3)

• Isometric strength

  A standard dynamometer will be used to measure isometric strength.

  Before and after FMT (4-20 weeks follow-up)

• Functional Autonomy: Global Index of the Latin American Group for Maturity (GDLAM)

  The Global Index of the Latin American Group for Maturity (GDLAM) will be used to assess three aspects of mobility: balance, gait speed, and lower limb strength for standing up from a chair

  Before and after FMT (4-20 weeks follow-up)

• Adverse effects after FMT registration

  Incidence of adverse effects after FMT will be recorded (serious and non-serious reactions) for safety and tolerability evaluation.

  after FMT (4-20 weeks follow-up)

Secondary Outcomes (17)

• Frailty index (FI)

  Before and after FMT (4-20 weeks follow-up)

• Lean and fat mass content

  Before and after FMT (4-20 weeks follow-up)

• Gut microbiota composition

  Before and after FMT (4-20 weeks follow-up)

• Metabolic function evaluation

  Before and after FMT (4-20 weeks follow-up)

• Working memory evaluation

  Before and after FMT (4-20 weeks follow-up)

Study Arms (2)

Placebo group

PLACEBO COMPARATOR

The first group receives a placebo (no FMT capsule)

Dietary Supplement: Placebo Capsule(s)

FMT group

EXPERIMENTAL

The second group receives FMT from young-trained donors

Dietary Supplement: FMT capsule

Interventions

FMT capsule DIETARY_SUPPLEMENT

A lyophilized gut microbiota capsule derived from a rigorously screened, healthy, and physically active donor, free of gastrointestinal diseases, antibiotic use, and chronic conditions. The donor diverse microbiome is supported by a nutrient-rich diet and active lifestyle. The lyophilization process preserves microbial integrity, offering a high-potency dose aimed at restoring and optimizing the gut microbiome of older adults. This intervention is specifically designed for older adults to enhance resilience to stress, cognitive function, muscular strength, and metabolic health. It is part of a controlled clinical study with follow-up assessments at weeks 1, 4, 8, and 20 post-intervention. This targeted approach distinguishes it from other microbiome-based therapies by focusing on comprehensive health benefits for an aging population.

FMT group

Placebo Capsule(s) DIETARY_SUPPLEMENT

A placebo capsule will be used in this study to serve as a control, allowing us to objectively assess the true effects of the lyophilized gut microbiota intervention. The use of a placebo is essential to eliminate bias and ensure that any observed outcomes can be confidently attributed to the actual intervention rather than to psychological or other non-specific effects. The placebo capsule will be identical in appearance, size, shape, and color to the interventional capsule to maintain blinding for both participants and researchers. This ensures that neither group knows which capsule is being administered, thereby preserving the study's integrity and validity by preventing any expectations or beliefs from influencing the results.

Placebo group

Eligibility Criteria

• Age: 65 Years - 84 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Individuals aged 65-84 years
• Men and women
• Involuntary total body weight variation in the last 6 months \< 10%
• Self-sufficiency (with a score \>60 on the Barthel index)
• Fasting plasma glucose ≤ 7.2 mmol/l or glycosylated hemoglobin (HbA1c) ≤ 8% in the last 6 months.
• Must be able to swallow capsules

You may not qualify if:

• Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg at selection
• Allergy to rifaximin
• Acute infection or inflammatory condition in the last 4 weeks
• Use of antibiotics in the last 12 weeks
• Use of probiotics in the last 12 weeks
• Hospitalization in the last 12 weeks
• Current or within the last 6 months use of insulin
• Difficulty swallowing (dysphagia)
• Diagnosis of Inflammatory bowel disease
• Diagnosis of Crohn's disease
• Diagnosis of Ulcerative colitis
• Diagnosis of Clostridium difficile infection
• Diagnosis of Colon cancer
• Treatment with immunosuppressive therapy for organ transplant
• Diagnosis of leukemia

Sponsors & Collaborators

• Gonzalo Jorquera, PhD: lead
• Universidad de los Andes, Chile: collaborator

Study Sites (2)

Clínica Universidad de los Andes

Santiago, Santiago Metropolitan, 7620157, Chile

Location

INTA - Universidad de Chile

Santiago, Santiago Metropolitan, 7830490, Chile

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Gonzalo Jorquera, PhD

  University of Chile

  STUDY DIRECTOR

• Ricardo Espinoza, MD

  Universidad de Los Andes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research director

Model Details: Our research is structured as a randomized, placebo-controlled, double-blind clinical trial.

Study Record Dates

• First Submitted: October 14, 2024
• First Posted: October 21, 2024
• Study Start: January 10, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

CL (2)