Imaging Skeletal Muscle Mitochondrial OXPHOS Activity In Acute Lymphoblastic Leukemia Survivors

NCT ID: NCT06819475

Last Updated: 2025-11-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-02
• Study Completion Date: 2028-01-31

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

Survivors

Adult survivor of acute lymphoblastic leukemia (ALL) enrolled in St. Jude Life Cohort (SJLIFE).

Group Type: EXPERIMENTAL

Magnetic Resonance Imaging

Intervention Type: 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 healthy controls and measure how muscle mitochondria produce energy to function.

Magnetic Resonance Spectroscopy

Intervention Type: 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 healthy controls and measure how muscle mitochondria produce energy to function.

Physical function assessment

Intervention Type: 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

Intervention Type: 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 healthy controls.

Skeletal muscle biopsy

Intervention Type: OTHER

Muscle biopsy will be used to evaluate muscle morphology, mitochondrial health and epigenetic differences in muscles of survivors and age/sex-matched healthy controls.

Muscle Ultrasound

Intervention Type: 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.

Control

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.

Group Type: EXPERIMENTAL

Magnetic Resonance Imaging

Intervention Type: 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 healthy controls and measure how muscle mitochondria produce energy to function.

Magnetic Resonance Spectroscopy

Intervention Type: 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 healthy controls and measure how muscle mitochondria produce energy to function.

Physical function assessment

Intervention Type: 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

Intervention Type: 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 healthy controls.

Skeletal muscle biopsy

Intervention Type: OTHER

Muscle biopsy will be used to evaluate muscle morphology, mitochondrial health and epigenetic differences in muscles of survivors and age/sex-matched healthy controls.

Muscle Ultrasound

Intervention Type: 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.

Interventions

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 healthy controls and measure how muscle mitochondria produce energy to function.

Intervention Type: 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 healthy controls and measure how muscle mitochondria produce energy to function.

Intervention Type: DIAGNOSTIC_TEST

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.

Intervention Type: 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 healthy controls.

Intervention Type: 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 healthy controls.

Intervention Type: OTHER

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.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

MRI; MRS

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- or Control-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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Puneet Bagga, PhD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Puneet Bagga, PhD

Role: CONTACT

referralinfo@stjude.org

866-278-5833

Puneet Bagga, PhD

Role: CONTACT

referralinfo@stjude.org

Facility Contacts

Puneet Bagga, PhD

Role: primary

referralinfo@stjude.org

866-278-5833

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

NCI-2024-09771

Identifier Type: OTHER

Identifier Source: secondary_id

MMICCS

Identifier Type: -

Identifier Source: org_study_id