Multidimensional Predictive Modeling to Understand Mechanisms of Exercise Response Heterogeneity in Older Adults (M3AX)

NCT06507189 | Recruiting DMC

• 1 other identifier: IRB-2024-0083
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 2

Brief Summary

Aging-related functional declines are thought to be caused by hallmark biological processes that ultimately manifest in physical, mental, and metabolic impairments that compromise healthspan and quality of life. Exercise is a multipotent treatment with promise to mitigate most aging hallmarks, but there is substantial variability in exercisƒe responsiveness. Combining endurance and resistance training in alignment with public health guidelines will be used to better understand variable exercise responsiveness in older adults with the ultimate goal of improving each older adult's capacity to attain the many health benefits of exercise.

Conditions

Aging; Aging Well

Outcome Measures

Primary Outcomes (2)

• Cardiorespiratory fitness (CRF)

  A primary outcome of this investigation is cardiorespiratory fitness (CRF). The CRF is the amount of oxygen (ml/kg) that is used during exercise and how efficient you are using that oxygen. The exercise used to measure oxygen uptake is a stationary bicycle with increasing intensity until you are able to maintain pace. Your expired air is collected with a mask or mouthpiece and analyzed with an oxygen and carbon dioxide sensor.

  23 weeks

• Functional muscle quality (fMQ)

  A primary outcome of this investigation is functional muscle quality (fMQ). This is a ratio of knee extension strength to thigh leanness. Knee extension strength is the maximum amount of weight you can successfully lift one time. Thigh lean mass is measured with the dual energy x-ray absorptiometry (DEXA). This is a common tool used to measure bone density, but it is very efficient at determining fat and lean masses partitioned in the body.

  23 weeks

Secondary Outcomes (5)

• Balance

  23 weeks

• Cognitive performance

  23 weeks

• Body composition

  23 weeks

• Metabolic health

  23 weeks

• Metabolic health

  23 weeks

Study Arms (2)

Phase I (12 weeks)

EXPERIMENTAL

In Interrogation, all participants will exercise train using an exercise prescription that is in accordance with current public health recommendations. At the end of Phase I participants will be classified into one of four categories: (1) CRF-/fMQ-, 2) CRF-/fMQ+, 3) CRF+/fMQ- and 4) CRF+/fMQ+).

Other: Combined endurance and resistance training

Phase II (10 weeks)

EXPERIMENTAL

Based on the Phase I categories of responsiveness, exercise training will be boosted in the three groups that are non-responsive in one or both outcomes. CRF-/fMQ+ will receive boosted ET, CRF+/fMQ- will receive boosted RT, and CRF-/fMQ- will receive boosting in both. All three of these classifications will also receive education on wearable device data and other free-living recommendations. Participants classified as CRF+/fMQ+ at the end of Phase I will be randomized to either continue the supervised exercise training or to free-living.

Other: Combined endurance and resistance training

Interventions

Combined endurance and resistance training OTHER

ET will consist of 3x/wk training (MWF) with MF being steady state cycling, treadmill, or elliptical at 70-75% HRR for 30 min and the W session being a 20 min high intensity interval session on a cycle ergometer (1 min on/off; 10 cycles) targeting 85-90% HRR. The treadmill and elliptical on M or F will be provided for variety but the mainstay will be cycle ergometry. On MF participants will complete 3 sets x 8-12 repetitions for leg press, knee extension, hamstring curl, chest press, seated row, overhead press, lat pulldown, triceps push-down, and biceps curl in superset fashion \[i.e., alternate between opposing muscle groups without rest (chest press followed by seated row)\] with a 60 s rest between supersets. Sets will be performed with load progression to ensure volitional fatigue in the 8-12 rep range. Core exercises (trunk flexion and extension) will also be included using bodyweight only for 3 sets.

Phase I (12 weeks); Phase II (10 weeks)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 60 or above
• Free of chronic disease
• No structured exercise program (2 or more bouts/wk) within previous 12 months
• Cognitively capable of providing informed consent

You may not qualify if:

• Neuromuscular or musculoskeletal disorder that would limit ability to perform the exercise and/or testing bouts
• Cardiopulmonary disorders or reduced breathing capacity
• Metabolic diseases including markers of liver disease (ALT \> 52 U/l) and type 2 diabetes (HbA1C ≥ 6.5, fasting blood glucose ≥ 126 mg/dl)
• Any other disease or disorder that would influence exercise response (e.g., chronic kidney disease, dementia, current cancer diagnosis or within 2 yr remission, cerebrovascular disease)
• History of chemotherapy within 5 years
• Any current infectious disease
• Life expectancy \< 1 year
• Insulin sensitizing/blood glucose lowering agents such as metformin
• High dose statin (dose equivalent to ≥40 mg/d simvastatin)
• Lidocaine allergy
• Regular tobacco use and/or vaping
• Excessive alcohol consumption (3 drinks/d or 7 drinks/wk for females; 4 drinks/d or 14 drinks/wk for males)
• BMI \< 35.0 kg/m2
• Unable to commit to \~6 months required to complete the study

Sponsors & Collaborators

• Florida Institute for Human and Machine Cognition: lead
• University of Florida: collaborator
• Oklahoma Medical Research Foundation: collaborator

Study Sites (2)

Florida Institute for Human and Machine Cognition

Pensacola, Florida, 32502, United States

RECRUITING

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

MeSH Terms

Interventions

Resistance Training

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Marcas Bamman

  Florida Institute for Human and Machine Cognition

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Craig Tuggle

CONTACT

205-352-6036; ctuggle@ihmc.org

Marcas Bamman, PHD

CONTACT

mbamman@ihmc.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Biospecimen investigators will be blinded from gender and age.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The overarching goal of this project is to determine factors contributing to response heterogeneity in outcomes key to healthy aging. The first phase of this two-phase trial will be focused on understanding the underlying biological mechanisms that explain/predict response heterogeneity and the second phase will test augmentation efforts to mitigate poor responsiveness while assessing whether the same or different mechanisms predict response when augmenting an individual's prescription in Phase II.

Study Record Dates

• First Submitted: June 27, 2024
• First Posted: July 18, 2024
• Study Start: January 27, 2025
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): August 31, 2029
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data will be transferred and monitored on the day of acquisition. Data will be identified with unique study identity.

Locations

US (2)