Multiple SclerosisMS-M3AXNCT07500727
Skeletal Muscle Aging and Responsiveness in Aged People With MS
A study testing Exercise trial consisting of both cardiovascular and strength training in people with Multiple Sclerosis and Aging, run by Oklahoma Medical Research Foundation at 1 site in United States.
Trial summary
The purposes of this study are to: 1) compare baseline muscle and cardiovascular health in older individuals (>60 years old) diagnosed with MS to age-matched people without MS, 2) determine muscle and whole body changes to an exercise training program, 3) determine if the muscle in a more affected leg in individuals… Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Multiple Sclerosis, Aging
- What is being tested?
- Exercise trial consisting of both cardiovascular and strength training
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Mar 2026to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Male or female aged 60 or above 2. Free of unmanaged chronic diseases other than multiple sclerosis 3. No structured exercise program (2 or more bouts/wk) within previous 6 months 4. Cognitively capable of providing informed consent 5. Must meet EDSS score between 2 to 5.5 during screening
Who cannot join
- 1. Neuromuscular or musculoskeletal disorder, other than multiple sclerosis, that would limit the ability to perform the exercise and/or testing bouts.
- 2. Cardiopulmonary disorders or reduced breathing capacity
- 3. Metabolic diseases including markers of liver disease (ALT > 52 U/dl) and type 2 diabetes (HbA1C ≥ 6.5, fasting blood glucose ≥ 126 mg/dl)
- 4. Taking any dose of metformin
- 5. Any other disease or disorder that would influence exercise response (e.g., chronic kidney disease, Alzheimer's, current cancer diagnosis or within 2 yr remission, cerebrovascular)
- 6. History of Chemotherapy within 5 years
Show all 18Show fewer
- 7. Unchangeable anticoagulant (Coumadin, Pradaxa, etc.) use. To be determined by clinical staff.
- 8. Insulin sensitizing/blood glucose lowering (e.g., metformin) or metabolic (GLP1 agonists) drugs.
- 9. High dose statin (40 mg and above)
- 10. Have a non-correctable visual impairment
- 11. Score less than 29 on the Symbol Digit Test
- 12. Received Botox for spasticity within the prior 3 months of study participation.
- 13. Cannot have any adjustments to Baclofen during study participation.
- 13. Unable to commit to ~4 months required to complete the study.
- 14. Lidocaine allergy
- 15. Tobacco use
- 16. Excessive alcohol consumption (3 drinks/d or 7 drinks/wk for females; 4 drinks/day or drinks/wk for males)
- 17. BMI greater than 35.0 kg/m2
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, 73104
Lena Fuentes, 4052717745, lena-fuentes@omrf.org
About this study
The purposes of this study are to: 1) compare baseline muscle and cardiovascular health in older individuals (>60 years old) diagnosed with MS to age-matched people without MS, 2) determine muscle and whole body changes to an exercise training program, 3) determine if the muscle in a more affected leg in individuals diagnosed with MS is different from the muscle of a less affected leg, and 4) if or how individuals diagnosed with MS adapt differently than age-matched people without MS to exercise training. Participation in this study will average 1.5 hours per visit, 3 visits per week, for approximately 4 months.
Read the detailed description
Disease-modifying therapies (DMT) are effective in reducing the risk of developing additional debilitating symptoms of multiple sclerosis (MS) and slowing disease progression, leading to better functional mobility outcomes and quality of life. As a result, people with MS (PwMS) are now more likely to maintain independence into their later years. Since older PwMS maintaining independence is a relatively recent phenomenon, there is virtually nothing known about how MS exacerbates the age-related loss of muscle mass and function (i.e., sarcopenia) or how PwMS adapt to interventions, such as exercise, that slow age-related declines. In addition, PwMS are known to be highly heterogeneous in functional ability, fatigue, and other physical factors. The investigators do not yet understand the aging trajectory in PwMS and if current treatment guidelines for aged individuals for overall health, including maintaining muscle mass and function, are effective in aged PwMS.
Aging-related functional declines are thought to be caused by hallmark biological processes that ultimately manifest in physical, mental, and metabolic impairments, which compromise healthspan and quality of life. Exercise is a multipotent treatment with promise to mitigate most aging hallmarks. However, there is substantial variability in how individuals respond to exercise training, which is termed inter-individual response heterogeneity (IRH). Low cardiorespiratory fitness (CRF, VO2max) and low functional muscle quality (fMQ; strength/muscle mass) are multi-system manifestations of the deterioration of the cellular hallmarks of aging, but both CRF and fMQ are modifiable with endurance exercise training (ET) and resistance exercise training (RT). It is yet to be determined how the hallmarks of aging influence IRH. For example, poor responder status could be caused by hallmark deterioration of mitochondrial function, ability to maintain proteostasis, or systemic inflammation.
The investigators are conducting an NIH funded clinical trial that hypothesizes that factors central to aging itself, such as proteostasis, mitochondrial energetics, and inflammation, are contributors to the multidimensional circuitry that determines whether an individual achieves the minimum clinically important difference (MCID) in CRF and/or fMQ with exercise training. The goal of the funded trial is to disentangle the complicated relationships between endogenous and exogenous factors that drive response variation to exercise. To accomplish this goal, investigators will use tissue (muscle and blood) sampling, multi-omics, extensive phenotyping, and multidimensional modeling. For the PHF proposal, investigators will leverage this ongoing clinical trial and enroll aged PwMS into the study. The overall goal of the current proposal is to establish baseline muscle and overall health characteristics, responsiveness to exercise training, and factors that give rise to heterogeneity of symptomology in aged PwMS.
- Conditions
- Multiple Sclerosis, Aging
- Being tested
- Exercise trial consisting of both cardiovascular and strength training
- Keywords
- exercise, skeletal muscle, metabolism, muscle, resistance training, training, cardiovascular training
- Medical subject headings
- Multiple Sclerosis, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise trial consisting of both cardiovascular and strength trainingOther
Also called endurance, strength
All participants will receive 12 weeks of combined ET and RT. All exercise is supervised with a certified trainer. All study staff are CPR trained. Progression of volume and intensity will occur during the ramp-up week and into the first week of training. The ramp-up period increases the number of sets, repetitions, and intensity to limit excessive muscle damage, soreness, and fatigue. Full volume training will be achieved by the end of week one and progression thereafter will be based on intensity. Participants will complete 3x/wk ET and 3x/week RT. Both ET and RT will be progressed on an individual level via monitoring of each session with pragmatic increases in cycling wattage, treadmill speed/grade, and weight lifted as needed. At the completion of training there will be a testing week that repeats the battery of testing completed during the wash-in period to determine responder status by the a priori designated MCIDs for CRF and fMQ.
| Study group | Role | What they receive |
|---|---|---|
| People with MS | Experimental | People with MS, 60 or older Receives: Other: Exercise trial consisting of both cardiovascular and strength training |
What is being measured
The primary outcome is the main question the study is designed to answer.
fMQ
Investigators will determine fMQ from bilateral one-repetition maximum (1RM) knee extension strength / bilateral thigh lean mass via dual-energy x-ray absorptiometry (DXA). Strength testing will be performed with a study trainer and DXA scanning will occur at Oklahoma Children's Hospital OU Health.
Measured: Week -3 and Week -2
CRF
Investigators will test CRF on a cycle ergometer using a continuous ramp protocol and ECG monitoring. The study clinician will monitor the ECG during testing while 1-2 other study personnel are administering the test. The ideal ramp for the individual is based on sex, body size, and initial assessments during familiarization
Measured: Enrollment to end of study at 18 weeks
Secondary outcomes (19)
Total and Regional Body Composition
Additional clinical phenotyping includes total and regional body composition scans using a GE Lunar iDXA and insulin resistance by HOMA-IR from fasting blood draws obtained from a study phlebotomist. An Octave biomarker panel will also be evaluated from blood draws.
Measured: Week -3 and Week -2
Muscle Biopsy
Investigators will use established methods to assess hallmarks of aging. Investigators will assess proteostasis in skeletal muscle using the final muscle biopsy sample from each leg with tracer-based proteomics. Investigators will use high-resolution respirometry on skeletal muscle mitochondria (Oroboros O2K respirometers) to determine both mitochondrial respiratory function and reactive oxygen species generation.
Measured: Week 1 and Week 12 Muscle Biopsy
Skeletal Muscle Phenotyping
For additional skeletal muscle phenotyping, investigators will perform histological analyses of skeletal muscle with immunohistochemical approaches using the well-established methods for cellular morphology, myofiber type distribution and size heterogeneity, fibrosis, vascularization (capillary supply), senescence/DNA damage, the presence of resident stem cells, and inflammatory cells including M1 macrophages10-12. Image analysis will be performed using the automated workflow in MyoVision.
Measured: Week 0, 6, and 12
Systemic Inflammation
Systemic inflammation will be assessed in serum samples using the MSD 10-plex cytokine panel. The cytokines tested, GM-CSF, IL-1alpha, IL-5, IL-7, IL-12, IL-15, IL-16, IL-17A, TNF-beta, and VEGF-A each have dynamic detection ranges respectively, 0.16-750 pg/mL, 0.09-278 pg/mL, 0.14-562 pg/mL, 0.12-563 pg/mL, 0.33-2,250 pg/mL, 0.15-525 pg/mL, 2.83-1,870 pg/mL, 0.31-3,650 pg/mL, 0.08-458 pg/mL, and1.12-562 pg/mL. Increased cytokines (high pg/mL) indicates a more active, heightened immune response with low cytokines (low pg/mL) indicating a normal resting immune system state.
Measured: Week 1 and Week 12
Muscle Inflammation
Investigators will also assess muscle inflammation in a targeted manner based on the fold change in expression of 3 receptors (TNFα, Fn14, IL-6) and associated intracellular signaling (p-STAT3, NFKB p-p65).
Measured: Week 1 and Week 12
Blood Biomarkers
Investigators also evaluate biomarkers in the blood using the Octave biomarker panel, a panel that measures 18 biomarkers to assess disease level in PwMS. Each biomarker generates an overall activity (DA) score from 1.0 to 10.0. Low DA score indicates more controlled, lower inflammation. A high DA score indicates high inflammation.
Measured: Week 1 and Week 12
Mobility and Balance
Mobility and balance testing will be accomplished via the well-established short physical performance battery (SPPB). The scale is a minimum score of 0 and maximum score of 12 with higher scores indicating better lower extremity function.
Measured: Week -3 and Week -2
Basic Cognitive Function and Balance
Investigators will assess basic cognitive function (reaction time, impulse control, visual processing speed) and balance with the Sway platform (Sway Medical). A score of 100 indicates perfect stability and lower scores indicate instability with the lowest score being 0.
Measured: Week -3 and Week -2
Participant's Self Evaluation of Physical, Mental, and Social Health
Investigators will use the validated Patient-Reported Outcomes Measurement Information System (PROMIS) mental health battery to evaluate participant's perspective on physical, mental, and social health. This test uses a T-score metric (typical range of 20-80) with a mean of 50, and a standard deviation of 10, higher scores indicating higher levels of metric measured with a maximum of >70 indicating severe for negative domains like pain, and scores minimum of <55 being within normal limits/absent of negative domain.
Measured: Week -3 and Week -2
Depression
Beck Depression Inventory II will be used to assess the presence and severity of depression symptoms within the past 2 weeks. Minimum score is 0 which indicates no presence of depression, and 63 being the highest score indicating the presence of severe depression.
Measured: Week -3 and Week -2
Circadian Rhythm
Circadian rhythm will be assessed using the Morningness-Eveningness Questionnaire. Minimum score of 16 indicates evening preference and highest score of 86 indicates morning preference.
Measured: Week -3 and Week -2
Sleep Quality
Pittsburgh Sleep Quality Index is a self-reported questionnaire that will be used to evaluate participant's sleep quality. 0 being the lowest score and 21 being the highest, with higher scores indicating poorer sleep quality.
Measured: Week -3 and Week -2
Fatigue
Fatigue will be evaluated using the Modified Fatigue Impact Scale (MFIS) questionnaire to rate fatigue in three categories: physical, cognitive, and psychosocial. A total score ranging from 0 to 84, where higher scores indicate greater fatigue impacting daily life.
Measured: Week -3 and Week -2
Gait Speed
A 10 Metre Walk Test will be administered to evaluate participant's gait speed and functional mobility. The total time taken to walk 10 meters is recorded, with slower speed indicating fall risks and higher speeds indicating better mobility.
Measured: Week -3 and Week -2
Functional Capacity
The 6 Minute Walk Test will be used to evaluate functional capacity, and measures the distance a participant can walk in 6 minutes. Longer distance covered indicates stronger gross functional capacity.
Measured: Week -3 and Week -2
Phenotyping Support with Multidimensional Interindividual Response Heterogeneity
To strengthen the phenotyping to support the multidimensional Interindividual Response Heterogeneity circuitry, investigators will use the Oura ring to monitor activity, sleep, mobility, temperature trends, and additional vital signs.
Measured: Week 1 through Week 13
Glucose Monitoring
To strengthen the phenotyping to support the multidimensional Interindividual Response Heterogeneity circuitry, subjects will wear a continuous glucose monitor (CGM) for ~7 d durations using the Dexcom G8 at the beginning and end of exercise training.
Measured: Week 1 and Week 12
Dietary Intake
Automated Self-Administered 24-Hour (ASA24) Dietary Assessment Tool will be used to evaluate participant's dietary intake.
Measured: Week -3 to -2, Week 0, Week 6, and Week 12
Blood Biomarkers
Investigators also evaluate biomarkers in the blood using the Octave biomarker panel, a panel that measures 18 biomarkers to assess disease level in PwMS. To assess inter-tissue communication, investigators will perform plasma EV long and small RNA-Seq, and whole muscle RNA-Seq and ATAC-Seq. All samples will be processed, sequenced, and analyzed.
Measured: Week 1 and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2026
- Study start6 Mar 2026 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oklahoma Medical Research Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benjamin F Miller, Ph.D., Principal investigator, Oklahoma Medical Research FoundationGabriel Pardo, Principal investigator, Oklahoma Medical Research Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07500727
- Sponsor's protocol ID
- 25-23-OMRF
- Other IDs
- 25-23
- Acronym
- MS-M3AX
- Status last verified
- Mar 2026
- First submitted
- 10 Mar 2026
- Last updated
- 30 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The data will be partially de-identified. IHMC will only have access to the participant's Subject ID, year of birth (and therefore age), and height/weight, which is necessary for normalization of outcomes such as cardiorespiratory fitness (VO2max testing).
Publications
Long DE, Peck BD, Lavin KM, Dungan CM, Kosmac K, Tuggle SC, Bamman MM, Kern PA, Peterson CA. Skeletal muscle properties show collagen organization and immune cell content are associated with resistance exercise response heterogeneity in older persons. J Appl Physiol (1985). 2022 Jun 1;132(6):1432-1447. doi: 10.1152/japplphysiol.00025.2022. Epub 2022 Apr 28.
PubMed 35482328Abbott CB, Lawrence MM, Kobak KA, Lopes EBP, Peelor FF 3rd, Donald EJ, Van Remmen H, Griffin TM, Miller BF. A Novel Stable Isotope Approach Demonstrates Surprising Degree of Age-Related Decline in Skeletal Muscle Collagen Proteostasis. Function (Oxf). 2021 May 10;2(4):zqab028. doi: 10.1093/function/zqab028. eCollection 2021.
PubMed 34124684Fuqua JD, Lawrence MM, Hettinger ZR, Borowik AK, Brecheen PL, Szczygiel MM, Abbott CB, Peelor FF 3rd, Confides AL, Kinter M, Bodine SC, Dupont-Versteegden EE, Miller BF. Impaired proteostatic mechanisms other than decreased protein synthesis limit old skeletal muscle recovery after disuse atrophy. J Cachexia Sarcopenia Muscle. 2023 Oct;14(5):2076-2089. doi: 10.1002/jcsm.13285. Epub 2023 Jul 14.
PubMed 37448295Miller B, Hamilton K, Boushel R, Williamson K, Laner V, Gnaiger E, Davis M. Mitochondrial respiration in highly aerobic canines in the non-raced state and after a 1600-km sled dog race. PLoS One. 2017 Apr 26;12(4):e0174874. doi: 10.1371/journal.pone.0174874. eCollection 2017.
PubMed 28445477Bubak MP, Davidyan A, O'Reilly CL, Mondal SA, Keast J, Doidge SM, Borowik AK, Taylor ME, Voloviceva E, Kinter MT, Britton SL, Koch LG, Stout MB, Lewis TL Jr, Miller BF. Metformin treatment results in distinctive skeletal muscle mitochondrial remodeling in rats with different intrinsic aerobic capacities. Aging Cell. 2024 Sep;23(9):e14235. doi: 10.1111/acel.14235. Epub 2024 Jun 24.
PubMed 38923664Graham ZA, Bubak MP, Raymond-Pope CJ, Cutter GR, McAdam JS, Tuggle SC, Siedlik JA, de Sousa LGO, Chappe EJ, Meece K, Kaur A, Ruiz BS, Bamman SC, Vanselow KM, Perry TW, Acosta-Arreguin JS, Bohmke NJ, Addison GJ, Bowers JM, Wright RL, Fuentes LD, Smith JE, Esser KA, Miller BF, Bodine SC, Bamman MM. Multidimensional Modeling to Maximize Adaptations to eXercise: the M3AX trial rationale and study design. J Appl Physiol (1985). 2025 Nov 1;139(5):1345-1356. doi: 10.1152/japplphysiol.00486.2025. Epub 2025 Sep 27.
PubMed 41015496Roberts BM, Lavin KM, Many GM, Thalacker-Mercer A, Merritt EK, Bickel CS, Mayhew DL, Tuggle SC, Cross JM, Kosek DJ, Petrella JK, Brown CJ, Hunter GR, Windham ST, Allman RM, Bamman MM. Human neuromuscular aging: Sex differences revealed at the myocellular level. Exp Gerontol. 2018 Jun;106:116-124. doi: 10.1016/j.exger.2018.02.023. Epub 2018 Feb 24.
PubMed 29481967Lee J, Song RJ, Musa Yola I, Shrout TA, Mitchell GF, Vasan RS, Xanthakis V. Association of Estimated Cardiorespiratory Fitness in Midlife With Cardiometabolic Outcomes and Mortality. JAMA Netw Open. 2021 Oct 1;4(10):e2131284. doi: 10.1001/jamanetworkopen.2021.31284.
PubMed 34714339Gaemelke T, Pedersen IS, Dalgas U, Hvid LG. Sarcopenia in older people with multiple sclerosis: A cross-sectional study. Mult Scler Relat Disord. 2025 Jan;93:106190. doi: 10.1016/j.msard.2024.106190. Epub 2024 Nov 25.
PubMed 39631136Powers SK, Lynch GS, Murphy KT, Reid MB, Zijdewind I. Disease-Induced Skeletal Muscle Atrophy and Fatigue. Med Sci Sports Exerc. 2016 Nov;48(11):2307-2319. doi: 10.1249/MSS.0000000000000975.
PubMed 27128663Naseri A, Nasiri E, Sahraian MA, Daneshvar S, Talebi M. Clinical Features of Late-Onset Multiple Sclerosis: a Systematic Review and Meta-analysis. Mult Scler Relat Disord. 2021 May;50:102816. doi: 10.1016/j.msard.2021.102816. Epub 2021 Feb 4.
PubMed 33571792Klistorner S, Barnett M, Parratt JDE, Yiannikas C, Wang C, Wang D, Shieh A, Klistorner A. Evolution of Chronic Lesion Tissue in Relapsing-Remitting Patients With Multiple Sclerosis: An Association With Disease Progression. Neurol Neuroimmunol Neuroinflamm. 2025 May;12(3):e200377. doi: 10.1212/NXI.0000000000200377. Epub 2025 Feb 28.
PubMed 40020214
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Skeletal Muscle Aging and Responsiveness in Aged People With MS
- ClinicalTrials.gov ID
- NCT07500727
- Acronym / sponsor ID
- MS-M3AX / 25-23-OMRF
- Conditions
- Multiple Sclerosis, Aging
- Keywords
- exercise, skeletal muscle, metabolism, muscle, resistance training, training, cardiovascular training
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Oklahoma Medical Research FoundationUniversity, hospital or other
- Study start
- 6 Mar 2026 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 30 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purposes of this study are to: 1) compare baseline muscle and cardiovascular health in older individuals (>60 years old) diagnosed with MS to age-matched people without MS, 2) determine muscle and whole body changes to an exercise training program, 3) determine if the muscle in a more affected leg in individuals diagnosed with MS is different from the muscle of a less affected leg, and 4) if or how individuals diagnosed with MS adapt differently than age-matched people without MS to exercise training. Participation in this study will average 1.5 hours per visit, 3 visits per week, for approximately 4 months.
Detailed description
Disease-modifying therapies (DMT) are effective in reducing the risk of developing additional debilitating symptoms of multiple sclerosis (MS) and slowing disease progression, leading to better functional mobility outcomes and quality of life. As a result, people with MS (PwMS) are now more likely to maintain independence into their later years. Since older PwMS maintaining independence is a relatively recent phenomenon, there is virtually nothing known about how MS exacerbates the age-related loss of muscle mass and function (i.e., sarcopenia) or how PwMS adapt to interventions, such as exercise, that slow age-related declines. In addition, PwMS are known to be highly heterogeneous in functional ability, fatigue, and other physical factors. The investigators do not yet understand the aging trajectory in PwMS and if current treatment guidelines for aged individuals for overall health, including maintaining muscle mass and function, are effective in aged PwMS.
Aging-related functional declines are thought to be caused by hallmark biological processes that ultimately manifest in physical, mental, and metabolic impairments, which compromise healthspan and quality of life. Exercise is a multipotent treatment with promise to mitigate most aging hallmarks. However, there is substantial variability in how individuals respond to exercise training, which is termed inter-individual response heterogeneity (IRH). Low cardiorespiratory fitness (CRF, VO2max) and low functional muscle quality (fMQ; strength/muscle mass) are multi-system manifestations of the deterioration of the cellular hallmarks of aging, but both CRF and fMQ are modifiable with endurance exercise training (ET) and resistance exercise training (RT). It is yet to be determined how the hallmarks of aging influence IRH. For example, poor responder status could be caused by hallmark deterioration of mitochondrial function, ability to maintain proteostasis, or systemic inflammation.
The investigators are conducting an NIH funded clinical trial that hypothesizes that factors central to aging itself, such as proteostasis, mitochondrial energetics, and inflammation, are contributors to the multidimensional circuitry that determines whether an individual achieves the minimum clinically important difference (MCID) in CRF and/or fMQ with exercise training. The goal of the funded trial is to disentangle the complicated relationships between endogenous and exogenous factors that drive response variation to exercise. To accomplish this goal, investigators will use tissue (muscle and blood) sampling, multi-omics, extensive phenotyping, and multidimensional modeling. For the PHF proposal, investigators will leverage this ongoing clinical trial and enroll aged PwMS into the study. The overall goal of the current proposal is to establish baseline muscle and overall health characteristics, responsiveness to exercise training, and factors that give rise to heterogeneity of symptomology in aged PwMS.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| People with MS | Experimental | Other: Exercise trial consisting of both cardiovascular and strength trainingPeople with MS, 60 or older |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 1. Male or female aged 60 or above 2. Free of unmanaged chronic diseases other than multiple sclerosis 3. No structured exercise program (2 or more bouts/wk) within previous 6 months 4. Cognitively capable of providing informed consent 5. Must meet EDSS score between 2 to 5.5 during screening
Key exclusion criteria (18 listed)
- 1. Neuromuscular or musculoskeletal disorder, other than multiple sclerosis, that would limit the ability to perform the exercise and/or testing bouts.
- 2. Cardiopulmonary disorders or reduced breathing capacity
- 3. Metabolic diseases including markers of liver disease (ALT > 52 U/dl) and type 2 diabetes (HbA1C ≥ 6.5, fasting blood glucose ≥ 126 mg/dl)
- 4. Taking any dose of metformin
- 5. Any other disease or disorder that would influence exercise response (e.g., chronic kidney disease, Alzheimer's, current cancer diagnosis or within 2 yr remission, cerebrovascular)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exercise trial consisting of both cardiovascular and strength trainingAlso: endurance, strengthAll participants will receive 12 weeks of combined ET and RT. All exercise is supervised with a certified trainer. All study staff are CPR trained. Progression of volume and intensity will occur during the ramp-up week and into the first week of training. The ramp-up period increases the number of sets, repetitions, and intensity to limit excessive muscle damage, soreness, and fatigue. Full volume training will be achieved by the end of week one and progression thereafter will be based on intensity. Participants will complete 3x/wk ET and 3x/week RT. Both ET and RT will be progressed on an individual level via monitoring of each session with pragmatic increases in cycling wattage, treadmill speed/grade, and weight lifted as needed. At the completion of training there will be a testing week that repeats the battery of testing completed during the wash-in period to determine responder status by the a priori designated MCIDs for CRF and fMQ. | Other | People with MS |
Primary outcome
fMQ
Time frame: Week -3 and Week -2
Investigators will determine fMQ from bilateral one-repetition maximum (1RM) knee extension strength / bilateral thigh lean mass via dual-energy x-ray absorptiometry (DXA). Strength testing will be performed with a study trainer and DXA scanning will occur at Oklahoma Children's Hospital OU Health.
CRF
Time frame: Enrollment to end of study at 18 weeks
Investigators will test CRF on a cycle ergometer using a continuous ramp protocol and ECG monitoring. The study clinician will monitor the ECG during testing while 1-2 other study personnel are administering the test. The ideal ramp for the individual is based on sex, body size, and initial assessments during familiarization
19 secondary outcomes
Total and Regional Body Composition
Time frame: Week -3 and Week -2
Muscle Biopsy
Time frame: Week 1 and Week 12 Muscle Biopsy
Skeletal Muscle Phenotyping
Time frame: Week 0, 6, and 12
Systemic Inflammation
Time frame: Week 1 and Week 12
Muscle Inflammation
Time frame: Week 1 and Week 12
Blood Biomarkers
Time frame: Week 1 and Week 12
Mobility and Balance
Time frame: Week -3 and Week -2
Basic Cognitive Function and Balance
Time frame: Week -3 and Week -2
Participant's Self Evaluation of Physical, Mental, and Social Health
Time frame: Week -3 and Week -2
Depression
Time frame: Week -3 and Week -2
Circadian Rhythm
Time frame: Week -3 and Week -2
Sleep Quality
Time frame: Week -3 and Week -2
Fatigue
Time frame: Week -3 and Week -2
Gait Speed
Time frame: Week -3 and Week -2
Functional Capacity
Time frame: Week -3 and Week -2
Phenotyping Support with Multidimensional Interindividual Response Heterogeneity
Time frame: Week 1 through Week 13
Glucose Monitoring
Time frame: Week 1 and Week 12
Dietary Intake
Time frame: Week -3 to -2, Week 0, Week 6, and Week 12
Blood Biomarkers
Time frame: Week 1 and Week 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2026.
- Background: PubMed 35482328Long DE, Peck BD, Lavin KM, Dungan CM, Kosmac K, Tuggle SC, Bamman MM, Kern PA, Peterson CA. Skeletal muscle properties show collagen organization and immune cell content are associated with resistance exercise response heterogeneity in older persons. J Appl Physiol (1985). 2022 Jun 1;132(6):1432-1447. doi: 10.1152/japplphysiol.00025.2022. Epub 2022 Apr 28.
- Background: PubMed 34124684Abbott CB, Lawrence MM, Kobak KA, Lopes EBP, Peelor FF 3rd, Donald EJ, Van Remmen H, Griffin TM, Miller BF. A Novel Stable Isotope Approach Demonstrates Surprising Degree of Age-Related Decline in Skeletal Muscle Collagen Proteostasis. Function (Oxf). 2021 May 10;2(4):zqab028. doi: 10.1093/function/zqab028. eCollection 2021.
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- Individual participant dataSharing planned: Undecided. The data will be partially de-identified. IHMC will only have access to the participant's Subject ID, year of birth (and therefore age), and height/weight, which is necessary for normalization of outcomes such as cardiorespiratory fitness (VO2max testing).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Benjamin F Miller, Ph.D. principal investigator
Oklahoma Medical Research Foundation
Gabriel Pardo principal investigator
Oklahoma Medical Research Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise trial consisting of both cardiovascular and strength training in people with Multiple Sclerosis and Aging, run by Oklahoma Medical Research Foundation at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lena Fuentes (4052717745, lena-fuentes@omrf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
fMQ (time frame: Week -3 and Week -2). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07500727, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2026.