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NCT Number: NCT06819475

Imaging Skeletal Muscle Mitochondrial OXPHOS Activity In Acute Lymphoblastic Leukemia Survivors

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.

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Key information

Conditions

Childhood Cancer Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Muscle Weakness Muscular Diseases Musculoskeletal Diseases Neoplasms Neoplasms by Histologic Type Nervous System Diseases Neurologic Manifestations Neuromuscular Manifestations Pathologic Processes Pathological Conditions, Signs and Symptoms Precursor Cell Lymphoblastic Leukemia-Lymphoma Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location status: Recruiting

Location contact

Puneet Bagga, PhD

CONTACT

[email protected]

888-226-4343

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Magnetic Resonance Imaging

Diagnostic Test

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.

Other names: MRI

Magnetic resonance spectroscopy

Diagnostic Test

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 names: MRS

Physical function assessment

Other

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

Other

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 biopsy

Other

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 Ultrasound

Diagnostic Test

Bilateral quadriceps and calf muscle ultrasound will be used to measure muscle volume by calculating the cross-sectional area using the Cavalieri method.

Primary outcomes

  1. To explore feasibility of MRI/MRS to measure OXPHOS capacity

    Time frame: Baseline

    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).

  2. To explore feasibility of 31P-MRS to measure OXPHOS capacity

    Time frame: Baseline

    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).

  3. To explore feasibility of 1H-MRS to measure OXPHOS capacity

    Time frame: Baseline

    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).

  4. To explore feasibility of CrCEST MRI to measure OXPHOS capacity

    Time frame: Baseline

    We will perform CrCEST MRI to map calf muscle Cr recovery kinetics (TCrCEST) following plantar flexion exercise (sec).

  5. To explore feasibility of Fat Fraction MRI to measure OXPHOS capacity

    Time frame: Baseline

    We will perform Dixon MRI to quantify intramuscular fat fraction (IFF %) in the calf.

  6. To explore feasibility of Muscle Ultrasound to measure OXPHOS capacity

    Time frame: Baseline

    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.

  7. To explore feasibility of Muscle Biopsy to measure OXPHOS capacity

    Time frame: Baseline

    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.

  8. To explore feasibility of mtDNA-CN to measure OXPHOS capacity

    Time frame: Baseline

    Peripheral blood samples will be drawn and analyzed for mtDNA-CN, metabolic and epigenetic profile and compared to the muscle sample.

Secondary outcomes

  1. Evaluate muscle strength to measure physical performance

    Time frame: Baseline

    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.

  2. Evaluate physical function to measure physical performance

    Time frame: Baseline

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Puneet Bagga, PhD

CONTACT

[email protected]

888-226-4343

Puneet Bagga, PhD

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

St. Jude Children's Research Hospital

Other

Registry information

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Feb 11, 2025
Registry last updated
May 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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