Muscle WeaknessNCT07531498
Muscle Aging Phenotypes in Childhood Cancer Survivors
An observational study of Muscle Weakness and Low Muscle Mass, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
Childhood cancer survivors experience premature declines in muscle mass, strength, and physical function that contribute to morbidity and early mortality. The biological mechanisms driving these impairments are heterogeneous and poorly understood. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Muscle Weakness, Low Muscle Mass, Sarcopenia
- What is being tested?
- Multimodal Muscle Imaging and Functional Assessment, Multimodal Muscle Imaging and Neuromuscular Assessment and Comprehensive Muscle Phenotyping
- How many people
- 533 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Sep 2026to May 2031
- Phase
- Observational
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study population includes adults aged 18 years or older enrolled in the St. Jude Lifetime Cohort (SJLIFE) who are childhood cancer survivors and community control participants without a cancer history. Eligible survivors are at least five years from primary cancer diagnosis and have reduced muscle mass and/or muscle strength based on age- and sex-specific z-scores. Survivors are categorized by prior exposure to peripheral neurotoxic cancer therapies. Community controls are frequency-matched by age and sex. All participants complete neuromuscular, imaging, and physical function assessments during a single study visit.
Who may be able to join
- Age 18 years old or older at time of consent and enrolled in SJLIFE.
- Participant (100 per group for a total of 400) is/has:
- Group 1: No cancer history
- Group 2: Age and sex specific relative lean mass z-score of less than -0.5 OR age and sex specific hand grip or isokinetic (60 degrees/sec) quadriceps strength z-score of <-0.5 AND exposure to a peripheral neurotoxin.
- Group 3: Age and sex specific relative lean mass z-score of less than -0.5 OR age and sex specific hand grip or isokinetic (60 degrees/sec) quadriceps strength z-score of <-0.5 AND NOT exposed to a peripheral neurotoxin.
- Group 4: Age and sex specific relative lean mass z-score of less than -0.5 AND age and sex specific hand grip strength or isokinetic (60 degrees/sec) quadriceps strength z-score of <-0.5 REGARDLESS of exposure status.
- Participant or legal guardian is able and willing to give informed consent.
Who cannot join
- Presence of implanted medical devices or metal that would interfere with MRI or MRS.
- Female Participant is pregnant.
- Body weight exceeding 300 pounds, due to MRI restrictions.
- Inability to lie flat on his/her back for 90 minutes or longer for MRI.
- Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
- Presence of known radiation-induced nerve injury.
- Prescence of pre-existing neurologic (non-cancer related) or who develop chronic neurologic disorders (i.e. Charcot Marie Tooth Disease, Downs, congenital brain injury).
- Participation on a lifestyle or medication clinical trial within the past 1 year.
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
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Kirsten Ness, PhD, 888-226-4343, referralinfo@stjude.org
Kirsten Ness, PhD
About this study
Childhood cancer survivors experience premature declines in muscle mass, strength, and physical function that contribute to morbidity and early mortality. The biological mechanisms driving these impairments are heterogeneous and poorly understood. This observational study aims to characterize distinct muscle health endotypes in adult survivors of childhood cancer using advanced imaging, neuromuscular testing, and functional assessment. Survivors with reduced muscle health and community controls will undergo multimodal magnetic resonance imaging and spectroscopy, nerve conduction studies, surface electromyography, body composition assessment, and physical performance testing during a single study visit integrated into an ongoing cohort evaluation. Identifying mechanistic endotypes of impaired muscle health will support development of targeted interventions to preserve function and improve long-term outcomes in childhood cancer survivors.
Primary Objective:
Read more
- Characterize reduced muscle health endotypes in childhood cancer survivors.
Secondary Objective:
- Identify specific treatment and lifestyle related risk factors for each reduced muscle health endotype.
Exploratory Objective:
- Host germline genetics will be associated with specific muscle endotypes.
Read the detailed description
Survivors of childhood cancer are at increased risk for early-onset frailty characterized by low lean mass, muscle weakness, and impaired physical function. Prior studies in the St. Jude Lifetime Cohort (SJLIFE) demonstrate that the prevalence of these impairments increases with age and is associated with a significantly higher risk of mortality. Traditional lifestyle and resistance training interventions have yielded only modest benefits, suggesting that superficially similar muscle phenotypes may be driven by distinct biological mechanisms.
Potential contributors to impaired muscle health in this population include peripheral nervous system dysfunction, altered motor unit activation, mitochondrial dysfunction, and muscle fat infiltration, resulting from cancer therapies, chronic health conditions, and lifestyle factors. Advanced imaging and neuromuscular phenotyping provide an opportunity to define distinct mechanistic "endotypes" that underlie reduced muscle health and to inform future precision interventions.
- Conditions
- Muscle Weakness, Low Muscle Mass, Sarcopenia
- Being tested
- Multimodal Muscle Imaging and Functional Assessment, Multimodal Muscle Imaging and Neuromuscular Assessment, Comprehensive Muscle Phenotyping, Integrated Neuromuscular and Imaging Evaluation
- Keywords
- Childhood Cancer Survivors, Adult Survivors of Childhood Cancer, Neuromuscular Function, Muscle Health
- Medical subject headings
- Muscle Weakness, Sarcopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multimodal Muscle Imaging and Functional AssessmentOther
Participants undergo comprehensive muscle phenotyping, including magnetic resonance imaging (MRI) to assess muscle cross-sectional area and fat fraction; magnetic resonance spectroscopy (¹H MRS and ³¹P MRS) to evaluate skeletal muscle mitochondrial energetics; body composition assessment using dual energy X ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA); nerve conduction velocity testing; surface electromyography (EMG); and standardized physical performance testing.
Multimodal Muscle Imaging and Neuromuscular AssessmentOther
Participants complete advanced neuromuscular and imaging assessments, including MRI-based evaluation of muscle structure and fat infiltration; magnetic resonance spectroscopy to assess mitochondrial oxidative metabolism; DXA and BIA for lean mass measurement; nerve conduction studies; surface electromyography during submaximal and maximal muscle activation; and physical function testing, performed during a single study visit.
Comprehensive Muscle PhenotypingOther
Participants undergo protocol-defined observational assessments including MRI and MRS of skeletal muscle, body composition analysis via DXA and BIA, neuromuscular testing with nerve conduction velocity and surface electromyography, and functional performance evaluations to characterize muscle health and underlying biological mechanisms.
Integrated Neuromuscular and Imaging EvaluationOther
Participants receive integrated phenotyping of muscle health using multimodal MRI and MRS imaging, neuromuscular testing with EMG and nerve conduction velocity, body composition assessment, and standardized physical performance measures to identify muscle aging endotypes.
| Study group | Role | What they receive |
|---|---|---|
| Community Controls | Adults with no history of cancer recruited from the community or non-first-degree relatives of St. Jude patients. Receives: Other: Multimodal Muscle Imaging and Functional Assessment | |
| Survivors With Low Lean Mass or Weakness and Peripheral Neurotoxin Exposure | Adult childhood cancer survivors with low lean mass and/or muscle weakness and documented exposure to peripheral neurotoxic therapies. Receives: Other: Multimodal Muscle Imaging and Neuromuscular Assessment | |
| Survivors With Low Lean Mass or Weakness Without Peripheral Neurotoxin Exposure | Adult childhood cancer survivors with low lean mass and/or muscle weakness and no history of exposure to peripheral neurotoxic therapies. Receives: Other: Comprehensive Muscle Phenotyping | |
| Survivors With Low Lean Mass and Muscle Weakness (Regardless of Neurotoxin Exposure) | Adult childhood cancer survivors meeting criteria for both low lean mass and muscle weakness, irrespective of treatment exposure. Receives: Other: Integrated Neuromuscular and Imaging Evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nerve conduction velocity (NCV) at rest and Electromyography (EMG) during submaximal and maximal force generation
Nerve conduction velocity (NCV) of sural sensory and tibial motor nerves will be performed using electromyography with standard landmarks for electrode placement. Compound Muscle Action Potential (CMAP) and Sensory Nerve Action Potential (SNAP) amplitudes are measured from negative to positive peak, and velocities calculated based on onset latency. NCV testing at rest and EMG during submaximal and maximal force generation will allow us to characterize the impact of the peripheral nervous system and the motor unit on muscle health.
Measured: Baseline
Creatinine recovery post exercise with magnetic resonance imaging (MRI)
The plantar flexion motion is performed during the dynamic CrCEST MRI and 31P MRS acquisitions to provide a standardized in scanner exercise stimulus that perturbs skeletal muscle energy metabolism in the calf muscles. We will perform Cr-weighted CEST MRI to map calf muscle Cr recovery kinetics following plantar flexion exercise using an ergometer device. MATLAB scripts will be used for post-processing CEST data. 31P-MRS is performed with 1H/31P dual-tuned surface/volume coil. PCr is determined by fitting the signal intensity of PCr following plantar flexion exercise to a mono-exponential function. We will acquire a steady state 31P-MR spectra for phosphorylated metabolite quantification.
Measured: Baseline
Intramyocellular and extramyocellular fat fraction in muscle during magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS)
Multiparametric MRI, 1H-MRS and Fat fraction MRI will be performed. 1H-MRS is a unique tool for studies of lipid metabolism because it is the only noninvasive method that separately quantifies Intramyocellular and extramyocellular lipids (IMCL and EMCL). Fat fraction is a metric for fat accumulation in healthy muscle tissue because of perturbed fatty acid oxidation. Dixon MRI sequence will be used to measure intramuscular fat fraction in legs and abdomen. MATLAB scripts are used for post- processing Dixon data. We will perform multiparametric quantitative MRI (PMID: 40172709). 1H-MRS is performed on a Siemens 3T scanner using Point RESolved Spectroscopy (PRESS) sequence (PMID: 3326459). A water-suppressed 1H spectrum will be acquired from a voxel positioned in gastrocnemius and soleus muscles. 1H- MRS data will be processed using LCModel (PMID: 8139448).
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2026
- Study start14 Sep 2026
- Primary completionMay 2030 (estimated)
- Study completionMay 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Muscle WeaknessStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 533 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Kirsten Ness, PhD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07531498
- Sponsor's protocol ID
- MUSCLEMAP
- Other IDs
- U01CA301480
- Status last verified
- Sep 2026
- First submitted
- 27 Mar 2026
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.