Trials Today

Imaging Skeletal Muscle Mitochondrial OXPHOS Activity In Acute Lymphoblastic Leukemia Survivors

Purpose

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.

Conditions

Childhood Cancer
Muscle Weakness

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: Yes

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 -1 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.

Study Design

Phase: N/A
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Screening
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Survivors	Adult survivor of acute lymphoblastic leukemia (ALL) enrolled in St. Jude Life Cohort (SJLIFE).	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 healthy controls and measure how muscle mitochondria produce energy to function. Other names: MRI 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. Other names: MRS 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 healthy 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 healthy 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.
Experimental 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.	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 healthy controls and measure how muscle mitochondria produce energy to function. Other names: MRI 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. Other names: MRS 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 healthy 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 healthy 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.

Recruiting Locations

St. Jude Children's Research Hospital
Memphis, Tennessee 38105

Contact:
Puneet Bagga, PhD
866-278-5833
referralinfo@stjude.org

More Details

NCT ID: NCT06819475
Status: Recruiting
Sponsor: St. Jude Children's Research Hospital

Study Contact

Puneet Bagga, PhD
866-278-5833
referralinfo@stjude.org

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.