NCT07500727

Brief 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 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for not_applicable multiple-sclerosis

Timeline
5mo left

Started Mar 2026

Shorter than P25 for not_applicable multiple-sclerosis

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress50%
Mar 2026Dec 2026

Study Start

First participant enrolled

March 6, 2026

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

March 10, 2026

Completed
20 days until next milestone

First Posted

Study publicly available on registry

March 30, 2026

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2026

Last Updated

March 30, 2026

Status Verified

March 1, 2026

Enrollment Period

10 months

First QC Date

March 10, 2026

Last Update Submit

March 25, 2026

Conditions

Multiple SclerosisAging

Keywords

exerciseskeletal musclemetabolismmuscleresistance trainingtrainingcardiovascular training

Outcome Measures

Primary Outcomes (2)

  • 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.

    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

    Enrollment to end of study at 18 weeks

Secondary Outcomes (19)

  • Total and Regional Body Composition

    Week -3 and Week -2

  • Muscle Biopsy

    Week 1 and Week 12 Muscle Biopsy

  • Skeletal Muscle Phenotyping

    Week 0, 6, and 12

  • Systemic Inflammation

    Week 1 and Week 12

  • Muscle Inflammation

    Week 1 and Week 12

  • +14 more secondary outcomes

Study Arms (1)

People with MS

EXPERIMENTAL

People with MS, 60 or older

Other: Exercise trial consisting of both cardiovascular and strength training

Interventions

Exercise trial consisting of both cardiovascular and strength trainingOTHER

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.

Also known as: endurance, strength
People with MS

Eligibility Criteria

Age60 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \. 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

You may not qualify if:

  • \. Neuromuscular or musculoskeletal disorder, other than multiple sclerosis, that would limit the 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/dl) and type 2 diabetes (HbA1C ≥ 6.5, fasting blood glucose ≥ 126 mg/dl)
  • \. Taking any dose of metformin
  • \. 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)
  • \. History of Chemotherapy within 5 years
  • \. Unchangeable anticoagulant (Coumadin, Pradaxa, etc.) use. To be determined by clinical staff.
  • \. Insulin sensitizing/blood glucose lowering (e.g., metformin) or metabolic (GLP1 agonists) drugs.
  • \. High dose statin (40 mg and above)
  • \. Have a non-correctable visual impairment
  • \. Score less than 29 on the Symbol Digit Test
  • \. Received Botox for spasticity within the prior 3 months of study participation.
  • \. Cannot have any adjustments to Baclofen during study participation.
  • \. Unable to commit to \~4 months required to complete the study.
  • \. Lidocaine allergy
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Related Publications (12)

  • 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). 132(6):1432-1447. doi: 10.1152/japplphysiol.00025.2022 (2022).

    BACKGROUND

  • Abbott 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). 2(4):zqab028. doi: 10.1093/function/zqab028 (2021). Erratum in: Function (Oxf). 3(3):zqac016. doi: 10.1093/function/zqac016 (2022).

    BACKGROUND

  • Fuqua 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. 14(5):2076-2089. doi: 10.1002/jcsm.13285 (2023).

    BACKGROUND

  • Miller 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. 12(4):e0174874. doi: 10.1371/journal.pone.0174874 (2017).

    BACKGROUND

  • Bubak MP, Davidyan A, O'Reilly CL, Mondal SA, Keast J, Doidge SM, Borowik AK, Taylor ME, Volovičeva 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. 23(9):e14235. doi: 10.1111/acel.14235 (2024).

    BACKGROUND

  • Graham ZA, Bubak MP, Raymond-Pope CJ, Cutter GR, McAdam JS, Tuggle SC, Siedlik JA, de Sousa LGO, Chappe EJ, Meece K, Kaur A, Ruiz BSR, 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). doi: 10.1152/japplphysiol.00486.2025. Epub ahead of print (2025).

    BACKGROUND

  • Roberts 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. 106:116-124. doi: 10.1016/j.exger.2018.02.023 (2018).

    BACKGROUND

  • Lee 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. 4(10):e2131284. doi: 10.1001/jamanetworkopen.2021.31284 (2021).

    BACKGROUND

  • Gaemelke, T., Pedersen, I. S., Dalgas, U. & Hvid, L. G. Sarcopenia in older people with multiple sclerosis: A cross-sectional study. Mult Scler Relat Disord. 93:106190, doi:10.1016/j.msard.2024.106190 (2025).

    BACKGROUND

  • Powers SK, Lynch GS, Murphy KT, Reid MB, Zijdewind I. Disease-Induced Skeletal Muscle Atrophy and Fatigue. Med Sci Sports Exerc. 48: 2307-2319, doi:10.1249/MSS.0000000000000975 (2016).

    BACKGROUND

  • Naseri 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. 50:102816, doi:10.1016/j.msard.2021.102816 (2021).

    BACKGROUND

  • Klistorner 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. 12:e200377, doi:10.1212/NXI.0000000000200377 (2025).

    BACKGROUND

MeSH Terms

Conditions

Multiple SclerosisMotor Activity

Interventions

Resistance Training

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System DiseasesBehavior

Intervention Hierarchy (Ancestors)

Exercise TherapyRehabilitationAftercareContinuity of Patient CarePatient CareTherapeuticsPhysical Therapy ModalitiesPhysical Conditioning, HumanExerciseMotor ActivityMovementMusculoskeletal Physiological PhenomenaMusculoskeletal and Neural Physiological Phenomena

Study Officials

  • Benjamin F Miller, Ph.D.

    Oklahoma Medical Research Foundation

    PRINCIPAL INVESTIGATOR

  • Gabriel Pardo

    Oklahoma Medical Research Foundation

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Lena Fuentes

CONTACT

4052717745lena-fuentes@omrf.org

Bobbette Miller

CONTACT

4052714214bobbette-miller@ou.edu

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
OTHER
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 10, 2026

First Posted

March 30, 2026

Study Start

March 6, 2026

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Last Updated

March 30, 2026

Record last verified: 2026-03

Locations

US(1)