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NCT Number: NCT07531498

Muscle Aging Phenotypes in Childhood Cancer Survivors

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:

- 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.

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Key information

Conditions

Muscle Weakness Atrophy Low Muscle Mass Muscular Atrophy Muscular Diseases Musculoskeletal Diseases Nervous System Diseases Neurologic Manifestations Neuromuscular Manifestations Pathologic Processes Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Sarcopenia Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location contact

Kirsten Ness, PhD

CONTACT

[email protected]

888-226-4343

Kirsten Ness, PhD

PRINCIPAL_INVESTIGATOR

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

Multimodal Muscle Imaging and Functional Assessment

Other

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 Assessment

Other

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 Phenotyping

Other

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 Evaluation

Other

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.

Primary outcomes

  1. Nerve conduction velocity (NCV) at rest and Electromyography (EMG) during submaximal and maximal force generation

    Time frame: Baseline

    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.

  2. Creatinine recovery post exercise with magnetic resonance imaging (MRI)

    Time frame: Baseline

    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.

  3. Intramyocellular and extramyocellular fat fraction in muscle during magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS)

    Time frame: Baseline

    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).

Study contacts

Contact information is provided by the study sponsor or research team.

Kirsten Ness, PhD

CONTACT

[email protected]

888-226-4343

Sponsors and collaborators

Lead sponsor

St. Jude Children's Research Hospital

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Important dates

Study start
2026
Primary completion
2030
Study completion
2031
First posted
Apr 15, 2026
Registry last updated
Jul 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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