Distinct Exercise Modalities on Gut Microbiome (DEMGUTS)

February 28, 2025 updated by: Faculty of Sports- Research Center in Physical Activity, Health and Leisure

Unraveling the Impact of Distinct Exercise Modalities on GUT Microbiome and Gut-derived Metabolites in Older Adults with Sarcopenia

Sarcopenia is a multifactorial muscular disease with detrimental clinical consequences, impairing physical function, functional independence, quality of life, need for long-term care and premature mortality. The development of sarcopenia is influenced by a complex interaction of multiple environmental and endogenous factors. However, to date, these complex mechanisms were unable to fully explain sarcopenia adverse health outcomes on skeletal muscle mass and function in older adults. Recently, the gut microbiome and its gut-derived metabolites have emerged as a key player in sarcopenia, with evidence suggesting that influence many underlying pathophysiological mechanisms (i.e., immune and inflammation system, anabolic resistance, insulin sensitivity, and energy production) that are involved in the development of sarcopenia. Current treatment guidelines of sarcopenia reinforce the role of exercise training, particularly resistance training to prevent adverse health outcomes. Exercise also stimulates favorable changes in gut microbiome composition and function, leading to host health benefits, regardless of nutrition. Nonetheless, the effects of exercise training on gut microbiome in patients with sarcopenia remains unclear, with existing evidence derived mainly from observational studies. In addition, the available evidence suggests that different types of exercise modalities may elicit distinct changes in gut microbiota composition but, to date, no study specifically addressed the optimal type of exercise modality in older adults considering the impact of gut microbiota composition or of gut-derived metabolites. Thus, despite the growing body of literature on the gut-muscle axis and sarcopenia, evidence from comparative studies focused on different exercise training regimens with a randomized controlled trial design in the impact of gut microbiota on skeletal muscle mass and function in sarcopenic patients is still lacking. Given that aerobic and resistance exercise stimulate different bioenergetic mechanisms and metabolic signaling pathways, we hypothesize that gut microbiome composition may be differently modulated by these distinct exercise regimens and that differently impact skeletal muscle mass and function, and physical performance in older adults. Leveraging current recruitment, logistics and human resources from a community exercise training program and the internal institutional collaborations, the investigative team will build a consecutive line of research to fill this literature gap and explore the impact of different exercise regimens on gut microbiome composition and gut-derived metabolites in these patients. The research team will start with a pilot single center 3-parallel arm open-label randomize control trial. Participants that meet the inclusion/exclusion criteria will be randomly assigned to: i) moderate aerobic exercise (AER); ii) resistance exercise (RES); or iii) concurrent exercise training (RES+AER). Participants in the experimental groups will engage in a supervised center-based exercise intervention (12-weeks, 3d/w, 60min/d). All participants will be assessed at i) baseline, ii) end of intervention (14 weeks) and iii) at close-out (26-weeks). The primary outcome will be the change in the relative abundance of Faecalibacterium prausnitzii and other SCFA producing bacteria after the intervention (14-weeks). Secondary outcomes include 1) change of Faecalibacterium prausnitzii relative abundance at close-out (26 weeks); 2) change of relative abundance of Lactobacillus and Bifidobacterium genera after the intervention and at the end of the follow-up. A set of complementary outcomes will also be assessed to broadly characterize the impact of each exercise intervention, including body composition, skeletal muscle function, functional performance and general gut microbiome composition. Other important confounding outcomes will be evaluated, including nutritional intake, daily physical activity, medication and supplementation use, and associated comorbidities. In the long term, the study team expects to contribute to clinical guidance and exercise prescription in older adults with sarcopenia using an evidence-based approach by exploring the optimal exercise mode to elicit favorable gut and skeletal muscle health benefits.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The gut microbiome is an important regulator of metabolism and has recently emerged as a relevant contributor to musculoskeletal health and disease, specifically to changes in skeletal muscle mass and function through a communication axis known as the gut-muscle axis. This posited gut-muscle communication pathway raises the attractive possibility that by manipulating the gut microbiota composition and function, scientists could mediate changes in skeletal muscle health and prevent sarcopenia adverse health outcomes. Thus, therapeutic strategies developed to modulate gut microbiome composition may have clinically meaningful implications in age-related muscle loss and physical function decline. Exercise has been shown to modulate the gut microbiome in older adults, but the evidence from well-designed randomized clinical trials is scarce. On the one hand, current guidelines recommend resistance training to reduce age-related skeletal muscle loss and physical function impairment. Still, on the other hand, aerobic exercise training is associated with increased microbiota diversity and an increase in SCFA-producing taxa, which has been linked to skeletal muscle health benefits and improved function. Given that these two exercise training regimens have different bioenergetic pathways, the study team hypothesized that each regimen promotes distinct alterations in gut microbiome composition. In contrast, combining both forms of exercise (resistance + aerobic) may lead to an added effect. Therefore, unraveling the impact of these exercise regimens on the gut microbiome is crucial to fill this relevant knowledge gap and to help clarify the optimal exercise regimen to manage sarcopenia. The research team long-term goal is to develop a consecutive line of research to explore the impact of these different exercise training regimens (i.e., resistance, aerobic, and concurrent exercise training) on gut microbiome composition and gut-derived metabolites and investigate its effects on skeletal muscle mass and function in older adults with sarcopenia. Methodology: Study design: This project will use a pilot 3-arm open-label randomized controlled trial (RCT), designed to evaluate the impact of distinct exercise training regimens on gut microbiome composition in older adults (age ≥ 60 years old) with sarcopenia. Methods: This study will use the recruitment, logistic and material resources from a community exercise program. Those who met our pre-screening criteria will be contacted by a study member, exposing the study's purposes, procedures, risk-discomforts, and benefits. Participants who agree will be invited to an in-person medical screening visit to assess the final inclusion/exclusion criteria and to provide their written informed consent (before enrollment). In this visit, volunteers will be evaluated through clinical examination, medication history, and a handgrip dynamometry test (an objective indicator of sarcopenia) to assess participants eligibility. Those who meet all inclusion/exclusion criteria will be randomly assigned (N= 69; 23/group) to three distinct exercise training programs: i) aerobic exercise (AER) training, ii) resistance exercise (RES), or iii) concurrent training (RES+AER). This project aims to randomize up to n=69 participants (n=23 / group) based on evidence from a recent systematic review with meta-analysis (11). Participants will engage in supervised center-based exercise interventions (12 weeks, 3d/w, 60min/d) consisting of either moderate aerobic training [60-70% HRmax], or resistance exercise [8 exercises/major muscle groups; 6-12 reps; 60-75% 1RM] or a combination of both (RES+AER). Assessments: All participants will be assessed at: i) baseline; ii) end of intervention (14-weeks); and iii) at close-out (26-weeks). Total length of the study is 26-weeks. At each study visit, participants will complete a skeletal muscle strength test, physical performance tests, assessment of body composition and provide a fasted blood, urine and fecal sample. Other important confounding variables will also be recorded including nutritional intake (using a 3-day diary), daily physical activity (using a physical activity tracker- wrist Fitbit), medication and supplementation use and associated comorbidities (assessed through medical and medication history questionnaire). Per the study design, the study team will also evaluate: a) retention and attrition rates; b) adherence to exercise intervention; c) safety; d) intervention effect on dependent outcomes. The success of recruitment and retention rates will be measured by the number of participants recruited, the number of drop-outs and losses to follow-up throughout the trial. Adherence to the exercise intervention will be carefully documented by study staff and will be measured by the number of sessions attended. Safety will be measured by the number and/or seriousness of adverse events attributable to the intervention and monitored and recorded by study staff throughout the trial. Objectives: Primary aim: The primary outcome will be the change in the relative abundance of Faecalibacterium prausnitzii and other SCFA producing bacteria after the intervention (14-weeks). Secondary outcomes include: 1) change of Faecalibacterium prausnitzii relative abundance at close-out (26-weeks); 2) change of relative abundance of Lactobacillus and Bifidobacterium genera after the intervention and at the end of the follow-up. Secondary aim: A set of complementary outcomes will also be assessed to broadly characterize the impact of each exercise intervention, including body composition, skeletal muscle function, functional performance and general gut microbiome composition. This broad set of outcomes will allow a comprehensive evaluation of the impact of these distinct exercise regimens on gut microbiota and on several health outcomes that are crucial for modulating gut microbiome and sarcopenia and may point to other mechanistic links that are currently undetermined. Expected Outcomes: The investigative team hypothesized that combining aerobic and resistance training will have a greater impact on the gut microbiome, specifically in increasing the relative abundance of Faecalibacterium prausnitzii and other SCFA-producing bacterial strains, an increase in skeletal muscle mass and strength, as well as enhanced physical performance measures in the concurrent exercise training group.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
69

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Portugal
      • Porto, Portugal
        • Recruiting
        • Faculty of Sports
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age: ≥ 60 years old
  • Sex: Men and women
  • Medical History: Objective indicators of sarcopenia- Handgrip strength: men < 27 kg and women < 16 kg; 4-m gait speed ≤ 0.8 m/s; Short Physical Performance Battery ≤ 8-point score; Chair stand test > 15 s; Time-up-go ≥ 20 s.
  • Physical Inactivity: International Physical Activity Questionnaire (IPAQ)- Portuguese version ≤ 150 minutes/week of moderate physical activity
  • Willingness to participate in all study procedures regardless of possible group allocation.

Exclusion Criteria:

  • Failure to provide consent.
  • Uncontrolled Hypertension: SBP> 180 mmHg or DBP> 110 mmHg.
  • History of coronary artery stenosis (>50%).
  • Heart Failure: Ejection fraction < 50%.
  • History of syncope at exertion.
  • History of hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, dilated cardiomyopathy or evidence in the previous 6 months of myocarditis or pericarditis.
  • Severe valvular heart disease.
  • Chronic kidney disease stage ≥ 4,8.
  • Chronic Obstructive Pulmonary Disease stage ≥ 3,9.
  • Musculoskeletal or neurodegenerative conditions that hinder exercise engagement.
  • Current participation in another structured exercise training program.
  • Inability to commit to study procedures or the exercise intervention throughout the study period.
  • Other condition or concern precluding safe participation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Resistance exercise training
The main part of RES group session will include free weights, weight machines and calisthenics. Loads will be set and adjusted based on 1 repetition maximum (1RM) method (details are described in Table 2). Exercises will be standardized but exercises may be adapted according to participants limitations. For RES group, the intervention was divided in 2 periods: a) 3- weeks adaptation phase (7-10 exercises; 1-2 sets; 15-20 reps; 40-60% 1RM); b) 9-weeks training phase (8 exercises; 3 sets; 6-12 reps; 70% 1RM; intensity measured by the rate of perceived exertion (RPE) 3-5 on category ratio 10 (CR10) scale progressing to RPE 6-8; resting 60-120 s between sets; 3-5 min between exercises) as recommended (29). Each session will aim at two anatomical regions (upper limbs, torso, back, lower limbs).
Behavioral: Concurrent exercise training
The experimental groups (AER, RES and AER+RES) will be enrolled in a supervised center-based exercise program for 12 weeks (3 days/week; 60 min/d). Sessions will occur in the morning, on alternating days of the week, and will be supervised by experienced exercise physiologists
Active Comparator: Aerobic exercise training
The main part of AER group sessions will include treadmill, stationary and elliptical bikes. The intensity throughout these sessions will be measured by heart rate maximum (HRmax) and by RPE 3-5 on CR10 scale progressing to RPE 6-8. The main part of AER group was divided in 3 periods; a) from week 1-2 (50% HRmax: 3x15 min+3min rest); b) week 3-4 (60% HRmax: 2x23min+5min rest); c) week > 5 (70% HRmax: continuous).
Behavioral: Concurrent exercise training
The experimental groups (AER, RES and AER+RES) will be enrolled in a supervised center-based exercise program for 12 weeks (3 days/week; 60 min/d). Sessions will occur in the morning, on alternating days of the week, and will be supervised by experienced exercise physiologists
Active Comparator: Concurrent exercise training
The main part of RES+AER group sessions will combine both exercise training protocols. The main parts of this group will start with resistance training using weights, weight machines and calisthenics combined with a main part of moderate aerobic exercises in the treadmill, stationary and elliptical bikes. This intervention was divided into 2 phases: a) a 3-week adaptation period (4-6 exercises; 1-2 sets; 15-20 reps; 40-60% 1RM); b) 9-weeks training phase (4 exercises; 3 sets; 6-12 reps; 60-70% 1RM; intensity measured by the RPE 3-5 on CR10 scale progressing to RPE 6-8; resting 60-120 s between sets; 3-5 min between exercises). Afterward, the moderate aerobic exercise training part will include three phases: 50% HRmax: 1x15 min); b) week 3-4 (60% HRmax: 1x23min); c) week > 5 (70% HRmax: continuous).
Behavioral: Concurrent exercise training
The experimental groups (AER, RES and AER+RES) will be enrolled in a supervised center-based exercise program for 12 weeks (3 days/week; 60 min/d). Sessions will occur in the morning, on alternating days of the week, and will be supervised by experienced exercise physiologists

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percent change in the relative abundance of Faecalibacterium prausnitzii and other SCFA producing bacteria
Time Frame: 14-weeks
The primary outcome will be the percent change in the relative abundance of Faecalibacterium prausnitzii and other SCFA producing bacteria after the intervention (14-weeks) using next generation sequencing on faecal samples
14-weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percent change of Faecalibacterium prausnitzii relative abundance at close-out
Time Frame: 26- weeks
Percent change of Faecalibacterium prausnitzii relative abundance at close-out (26-weeks)using next generation sequencing on faecal samples;
26- weeks
Percent change of relative abundance of Lactobacillus and Bifidobacterium genera after the intervention and at the end of the follow-up
Time Frame: 26- weeks
Percent change of relative abundance of Lactobacillus and Bifidobacterium genera after the intervention using next generation sequencing on faecal samples
26- weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Body composition
Time Frame: 14- weeks
Body composition will be assessed by whole-body dual-energy X-ray absorptiometry to measure percent body fat mass, percent lean mass, appendicular lean mass
14- weeks
Skeletal muscle function
Time Frame: 14-weeks
Dominant lower limb knee extension and flexion muscle strength will be assessed through a isokinetic dynamometer to measure peak torque of extension and flexion total work (J)
14-weeks
Nutritional Intake
Time Frame: 14-weeks
Participants will be instructed to record all food and beverage intake for three consecutive days using a 3-day food diary prior to the fecal collection day
14-weeks
Physical performance
Time Frame: 14-weeks
participants will be evaluated using gait speed, the 30-second chair rise, the Short Physical Performance Battery (SPPB) and the 400 meter walk test. To assess gait speed, we will use the 4-meter usual walk test with speed time. The SPPB is a composite test battery that includes assessment of gait speed, a balance test, and a chair stand test. Each test is scored 4 points until a maximum score of 12 points. the 400-meter walk test, participants are asked to complete 20 laps of 20 m, each lap as fast as possible. This test evaluates walking ability and endurance.
14-weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Faculty of Sports- Research Center in Physical Activity, Health and Leisure

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Unit for Multidisciplinary Research in Biomedicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Liliana C. Baptista, PhD, Faculty of Sport, University of Porto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 20, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 9, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CEFADE 04 2024

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

This project contemplates a plan to disseminate knowledge using specific methods and actions, distinct digital platforms and directed to different audiences. The goal is to disseminate the novel findings that may result from this project as soon as possible upon completion and make them publicly available to all that may benefit with it. As soon as the last participant finishes his last assessment visit, the study team members will start to adequately analyze the study data. The study team will prepare abstracts and manuscripts for publication. Preliminary results that may seem adequate for scientific meetings will be prepared in accordance and presented at national or international relevant conferences.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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