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Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
Yes

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.

Study Design

Phase
Study Type
Observational
Observational Model
Cohort
Time Perspective
Cross-Sectional

Arm Groups

ArmDescriptionAssigned Intervention
Community Controls Adults with no history of cancer recruited from the community or non-first-degree relatives of St. Jude patients.
  • Other: Multimodal Muscle Imaging and Functional Assessment
    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.
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.
  • Other: Multimodal Muscle Imaging and Neuromuscular Assessment
    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.
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.
  • Other: Comprehensive Muscle Phenotyping
    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.
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.
  • Other: Integrated Neuromuscular and Imaging Evaluation
    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.

Recruiting Locations

St. Jude Children's Research Hospital
Memphis, Tennessee 38105
Contact:
Kirsten Ness, PhD
888-226-4343
referralinfo@stjude.org

More Details

Status
Recruiting
Sponsor
St. Jude Children's Research Hospital

Study Contact

Kirsten Ness, PhD
888-226-4343
referralinfo@stjude.org

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.