Imaging Skeletal Muscle Mitochondrial OXPHOS Activity In Acute Lymphoblastic Leukemia Survivors
2 other identifiers
interventional
60
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Jun 2025
Typical duration for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 8, 2025
CompletedFirst Posted
Study publicly available on registry
February 11, 2025
CompletedStudy Start
First participant enrolled
June 2, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2028
April 23, 2026
April 1, 2026
1.7 years
January 8, 2025
April 22, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (8)
To explore feasibility of MRI/MRS to measure OXPHOS capacity
Multimodal MR imaging will be performed in two appointments. The first appointment will consist of Part 1 (approximately 1 hour) and Part 2 (approximately 30 minutes). There will be a 5-10 minute break between the two parts. The second appointment will consist of Part 1 (approximately 1 hour).
Baseline
To explore feasibility of 31P-MRS to measure OXPHOS capacity
This will be performed with a 7-cm diameter 1H/31P dual-tuned surface/volume coil using an unlocalized free induction decay (FID) sequence: number of points = 512, averages = 2-5, and TR = 2.4-5 seconds, with 4 dummy scans. TPCr is determined by fitting the signal intensity of PCr following plantar flexion exercise to a mono-exponential function. Additionally, we will acquire a steady state 31P-MR spectra for phosphorylated metabolite quantification (sec).
Baseline
To explore feasibility of 1H-MRS to measure OXPHOS capacity
This will be performed on a Siemens 3T scanner using Point RESolved Spectroscopy (PRESS) 31 sequence. A water-suppressed 1H MR spectrum will be acquired from a voxel positioned in gastrocnemius and soleus muscles. 1H MRS data will be processed using LCModel providing the metabolite levels (mM).
Baseline
To explore feasibility of CrCEST MRI to measure OXPHOS capacity
We will perform CrCEST MRI to map calf muscle Cr recovery kinetics (TCrCEST) following plantar flexion exercise (sec).
Baseline
To explore feasibility of Fat Fraction MRI to measure OXPHOS capacity
We will perform Dixon MRI to quantify intramuscular fat fraction (IFF %) in the calf.
Baseline
To explore feasibility of Muscle Ultrasound to measure OXPHOS capacity
Participants will lay supine with legs fully extended with their ankles stabilized in neutral. Customized templates will be strapped on the thigh and consist of five to eight 2-cm slices with a 1-cm gap between slices. Using transmission gel, a continuous, single view will be measured by transversely moving the probe across the thigh in approximately four seconds to acquire images of the rectus femoris (RF) and the vastus lateralis (VL), ensuring minimal pressure is applied to the skin to avoid muscle compression. Bilateral calf muscle CSA will be assessed in the same manner.
Baseline
To explore feasibility of Muscle Biopsy to measure OXPHOS capacity
A vacuum-assisted biopsy device and ultrasound guidance will be used to obtain skeletal muscle samples. The procedure is performed under local anesthesia with the patient in supine position. The needle will be inserted into the vastus lateralis, accessed through a 2-3 mm incision, under local anesthesia. When the needle is removed, a small section of muscle will remain with the needle. Two samples will be obtained during the procedure. One sample will be analyzed for satellite cell content and morphology. The second sample will be analyzed for mtDNA-CN and epigenetic profile.
Baseline
To explore feasibility of mtDNA-CN to measure OXPHOS capacity
Peripheral blood samples will be drawn and analyzed for mtDNA-CN, metabolic and epigenetic profile and compared to the muscle sample.
Baseline
Secondary Outcomes (2)
Evaluate muscle strength to measure physical performance
Baseline
Evaluate physical function to measure physical performance
Baseline
Study Arms (2)
Survivors
EXPERIMENTALAdult survivor of acute lymphoblastic leukemia (ALL) enrolled in St. Jude Life Cohort (SJLIFE).
Control
EXPERIMENTALControl participants are not a close relative of someone who has received treatment for childhood cancer or a similar illness; age/sex-matched healthy volunteers and recruited from SJLIFE Control cohort and may be recruited from new SJLIFE Controls.
Interventions
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 healthy controls and measure how muscle mitochondria produce energy to function.
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 healthy controls and measure how muscle mitochondria produce energy to function.
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.
Peripheral blood sample will be used to evaluate muscle morphology, mitochondrial health and epigenetic differences in the muscles of survivors and age/sex-matched healthy controls.
Muscle biopsy will be used to evaluate muscle morphology, mitochondrial health and epigenetic differences in muscles of survivors and age/sex-matched healthy controls.
Bilateral quadriceps and calf muscle ultrasound will be used to measure muscle volume by calculating the cross-sectional area using the Cavalieri method.
Eligibility Criteria
You may qualify if:
- 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- or Control-Participant is able and willing to give informed consent
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Puneet Bagga, PhD
St. Jude Children's Research Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- SCREENING
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 8, 2025
First Posted
February 11, 2025
Study Start
June 2, 2025
Primary Completion (Estimated)
March 1, 2027
Study Completion (Estimated)
January 1, 2028
Last Updated
April 23, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data will be made available at the time of article publication.
- Access Criteria
- Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
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.