Imaging Skeletal Muscle Mitochondrial OXPHOS Activity In Acute Lymphoblastic Leukemia Survivors
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Physical function assessment, Peripheral blood sample.
- Who it may be relevant to
- Registry conditions: Childhood Cancer, Muscle Weakness. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
The participants are being asked to take part in this trial, because the participant is a survivor of childhood cancer or agreed to be part of a volunteer group to understand the relation between cancer and cancer treatment and muscle weakness in survivors of Acute Lymphoblastic Leukemia (ALL). ALL is cancer of the blood and bone marrow. Primary Objective • To compare muscle mtOXPHOS activity and satellite cell content among ALL survivors and controls. Secondary Objective * To evaluate the association between muscle mtOXPHOS, muscle satellite cell content and physical performance in ALL survivors. * To evaluate the association of muscle morphology and epigenetics with muscle mtOXPHOS in ALL survivors.
Detailed description
This study hypothesizes that sarcopenia (low lean mass and muscle weakness), the central components of frailty, result from cancer- and or treatment-related impairment of cellular function within skeletal myocytes. Impaired mitochondrial oxidative phosphorylation (mtOXPHOS) is a hallmark of aging and implicated in skeletal muscle (muscle) weakness and lowered physical performance with normal aging. There is a lack of understanding of how the dysfunctional mitochondrial capacity affects the individual muscle groups in the lower extremities of the survivors.
This pilot study will explore the feasibility of non-invasive metabolic imaging to measure the major muscle groups in the calf muscle mtOXPHOS in childhood survivors of Acute Lymphoblastic Leukemia (ALL) in SJLIFE cohort by incorporating magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in survivors and age/sex-matched healthy volunteers (Controls). Control participants will be recruited from SJLIFE control cohort and may be recruited from new SJLIFE controls; The MRI/MRS findings will be correlated with clinically ascertained muscle phenotype; and will explore and describe differences in muscle morphology, epigenetics, mtDNA-CN between survivors and controls using peripheral blood and muscle biopsies, and their association with MRI/MRS findings.
Survivor and Control participants will be asked to have two MRI sessions; a physical function, and a muscle ultrasound assessment done during SJLIFE Human Performance Lab (HPL). Participants will be asked to give a peripheral blood sample and muscle sample. MR imaging will be performed in two appointments.
Interventions
- Diagnostic test Magnetic Resonance Imaging
Non-invasive MRI will be used to measure the major muscle groups in the calf muscle mtOXPHOS in childhood survivors of Acute Lymphoblastic Leukemia (ALL) in SJLIFE cohort and community controls and measure how muscle mitochondria produce energy to function. - Diagnostic test Magnetic Resonance Spectroscopy
Non-invasive MRS will be used to measure the major muscle groups in the calf muscle mtOXPHOS in childhood survivors of Acute Lymphoblastic Leukemia (ALL) in SJLIFE cohort and community controls and measure how muscle mitochondria produce energy to function. - Other Physical function assessment
As part of the SJLIFE visit in the Human Performance Lab, the participant's physical health will be assessed by testing muscle strength, physical function, and lean muscle mass. - Other Peripheral blood sample
Peripheral blood sample will be used to evaluate muscle morphology, mitochondrial health and epigenetic differences in the muscles of survivors and age/sex-matched community controls. - Other Skeletal muscle biopsy
Muscle biopsy will be used to evaluate muscle morphology, mitochondrial health and epigenetic differences in muscles of survivors and age/sex-matched community controls. - Diagnostic test Muscle Ultrasound
Bilateral quadriceps and calf muscle ultrasound will be used to measure muscle volume by calculating the cross-sectional area using the Cavalieri method.
Primary outcome measures
- To explore feasibility of MRI/MRS to measure OXPHOS capacity [Time frame: Baseline]
- To explore feasibility of 31P-MRS to measure OXPHOS capacity [Time frame: Baseline]
- To explore feasibility of 1H-MRS to measure OXPHOS capacity [Time frame: Baseline]
- To explore feasibility of CrCEST MRI to measure OXPHOS capacity [Time frame: Baseline]
- To explore feasibility of Fat Fraction MRI to measure OXPHOS capacity [Time frame: Baseline]
- To explore feasibility of Muscle Ultrasound to measure OXPHOS capacity [Time frame: Baseline]
- To explore feasibility of Muscle Biopsy to measure OXPHOS capacity [Time frame: Baseline]
- To explore feasibility of mtDNA-CN to measure OXPHOS capacity [Time frame: Baseline]
Secondary outcome measures (2)
- Evaluate muscle strength to measure physical performance [Time frame: Baseline]
- Evaluate physical function to measure physical performance [Time frame: Baseline]
Eligibility criteria
Inclusion criteria
- Survivor- or Control-Participant is age 18 years old or older at time of consent and enrolled in SJLIFE.
- Survivor- Participant is childhood ALL survivor
- Survivor- or Control Participant has low muscle mass as defined by relative lean mass z-score of less than or equal to -0.5 SD (lean mass divided by height in meters squared).
- Survivor - Participant is able and willing to give informed consent
Exclusion criteria
- Survivor-Participant has history of cranial radiation.
- Survivor- or Control-Participant has implanted medical devices or metal that would interfere with MRI or MRS
- Female Survivor- or Control-Participant is pregnant.
- Survivor- or Control-Participant is taking anticoagulants (e.g. aspirin, apixaban, coumadin, edoxaban, rivaroxaban)
- Survivor- or Control-Participant weighs more than 300 pounds.
- Survivor- or Control-Participant is allergic to local anesthetic (i.e., lidocaine, bupivacaine).
- Survivor- or Control-Participant cannot lie flat on his/her back for 90 minutes or longer
- Survivor- or Control-Participant has a current history of peripheral motor neuropathy.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Screening
Study locations
United States · 1 center
- St. Jude Children's Research Hospital — Memphis
Identifiers
NCT: NCT06819475 · MMICCS · NCI-2024-09771