Childhood CancerNCT06819475
Imaging Skeletal Muscle Mitochondrial OXPHOS Activity In Acute Lymphoblastic Leukemia Survivors
A study testing Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy and Physical function assessment in people with Childhood Cancer and Muscle Weakness, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Childhood Cancer, Muscle Weakness
- What is being tested?
- Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy and Physical function assessment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jun 2025to Jan 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Puneet Bagga, PhD contact
United States1 site, 1 recruiting
- Recruiting
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Puneet Bagga, PhD, 888-226-4343, referralinfo@stjude.org
About this study
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.
Read the 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.
- Conditions
- Childhood Cancer, Muscle Weakness
- Being tested
- Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Physical function assessment, Peripheral blood sample, Skeletal muscle biopsy
- Keywords
- Survivor, Acute Lymphoblastic Leukemia, Adult, ALL, Healthy Volunteer
- Medical subject headings
- Neoplasms, Muscle Weakness, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Resonance ImagingDiagnostic test
Also called MRI
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.
Magnetic Resonance SpectroscopyDiagnostic test
Also called MRS
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.
Physical function assessmentOther
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 sampleOther
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.
Skeletal muscle biopsyOther
Muscle biopsy will be used to evaluate muscle morphology, mitochondrial health and epigenetic differences in muscles of survivors and age/sex-matched community controls.
Muscle UltrasoundDiagnostic test
Bilateral quadriceps and calf muscle ultrasound will be used to measure muscle volume by calculating the cross-sectional area using the Cavalieri method.
| Study group | Role | What they receive |
|---|---|---|
| Survivors | Experimental | Adult survivor of acute lymphoblastic leukemia (ALL) enrolled in St. Jude Life Cohort (SJLIFE). Receives: Diagnostic Test: Magnetic Resonance Imaging; Diagnostic Test: Magnetic Resonance Spectroscopy; Other: Physical function assessment; Other: Peripheral blood sample; Other: Skeletal muscle biopsy; Diagnostic Test: Muscle Ultrasound |
| Control | Experimental | Control 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. Receives: Diagnostic Test: Magnetic Resonance Imaging; Diagnostic Test: Magnetic Resonance Spectroscopy; Other: Physical function assessment; Other: Peripheral blood sample; Other: Skeletal muscle biopsy; Diagnostic Test: Muscle Ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline
Secondary outcomes (2)
Evaluate muscle strength to measure physical performance
Isokinetic quadricep and ankle strength (Biodex System 4) will be evaluated bilaterally, measured as peak torque (Newton-meters (Nm)) per kilogram (kg) of body weight during cyclical contractions at standard speeds. The average maximum value from each side is used.
Measured: Baseline
Evaluate physical function to measure physical performance
The Timed Up and Go42 captures time to stand, walk 3m, and return to a seated position. The Six Minute Walk tests functional endurance, recorded as the max distance walked 6 minutes.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2025
- Study start2 Jun 2025
- Primary completionJul 2027 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Childhood CancerStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Puneet Bagga, PhD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06819475
- Sponsor's protocol ID
- MMICCS
- Other IDs
- NCI-2024-09771
- Status last verified
- Sep 2026
- First submitted
- 8 Jan 2025
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.