Muscle Aging Phenotypes in Childhood Cancer Survivors
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorSt. Jude Children's Research Hospital
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Age 18 years old or older at time of consent and enrolled in SJLIFE.
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.
Disqualifiers
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.
Trial 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.
Trial design
Design model
Cohort
Time perspective
Cross-sectional
Treatments tested in this trial
Multimodal Muscle Imaging and Functional Assessment
Other interventionParticipants 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 interventionParticipants 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 interventionParticipants 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 interventionParticipants 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.
Treatment groups
533 Participants
are divided into 4 treatment groupsGroup A: Community Controls1 intervention
Group B: Survivors With Low Lean Mass or Weakness and Peripheral Neurotoxin Exposure1 intervention
Group C: Survivors With Low Lean Mass or Weakness Without Peripheral Neurotoxin Exposure1 intervention
Group D: Survivors With Low Lean Mass and Muscle Weakness (Regardless of Neurotoxin Exposure)1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Baseline2
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.
Time frame
Baseline3
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).
Time frame
BaselineSponsors and contacts
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St. Jude Children's Research Hospital
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Source ClinicalTrials.gov