Distinct Exercise Modalities on Gut Microbiome

NCT06545123 | Recruiting

• 1 other identifier: CEFADE 04 2024
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sarcopenia; Older Adults

Keywords

Gut Microbiome; Exercise; Metabolomics; Physical function

Outcome Measures

Primary Outcomes (1)

• Percent change in the relative abundance of Faecalibacterium prausnitzii and other SCFA producing bacteria

  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 Outcomes (2)

• Percent change of Faecalibacterium prausnitzii relative abundance at close-out

  26- weeks

• Percent change of relative abundance of Lactobacillus and Bifidobacterium genera after the intervention and at the end of the follow-up

  26- weeks

Other Outcomes (4)

• Body composition

  14- weeks

• Skeletal muscle function

  14-weeks

• Nutritional Intake

  14-weeks

Study Arms (3)

Resistance exercise training

ACTIVE COMPARATOR

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

Aerobic exercise training

ACTIVE COMPARATOR

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

Concurrent exercise training

ACTIVE COMPARATOR

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

Interventions

Concurrent exercise training BEHAVIORAL

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

Aerobic exercise training; Concurrent exercise training; Resistance exercise training

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Faculty of Sports- Research Center in Physical Activity, Health and Leisure: lead
• Unit for Multidisciplinary Research in Biomedicine: collaborator

Study Sites (1)

Faculty of Sports

Porto, Portugal

RECRUITING

Related Publications (1)

• Merelim AS, Zacca R, Moreira-Goncalves D, Costa PP, Baptista LC. Distinct exercise modalities on GUT microbiome in sarcopenic older adults: study protocol of a pilot randomized controlled trial. Front Med (Lausanne). 2025 Mar 5;12:1504786. doi: 10.3389/fmed.2025.1504786. eCollection 2025.

  PMID: 40109720 DERIVED

MeSH Terms

Conditions

Sarcopenia; Motor Activity

Condition Hierarchy (Ancestors)

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Behavior

Study Officials

• Liliana C. Baptista, PhD

  Faculty of Sport, University of Porto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liliana C. Baptista, PhD

CONTACT

+351 220 425 239; lbaptista@fade.up.pt

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: July 20, 2024
• First Posted: August 9, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)