Health TrialsbyHealthPanel

Imaging Skeletal Muscle Mitochondrial OXPHOS Activity In Acute Lymphoblastic Leukemia Survivors

ConditionsChildhood CancerMuscle Weakness
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorSt. Jude Children's Research Hospital

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

  • 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.

  • Physical function assessment

    Other intervention

    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 intervention

    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 intervention

    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.

Treatment groups

60 Participants
are divided into 2 treatment groups
Group A: SurvivorsExperimental treatment 6 interventions
Group B: ControlExperimental treatment 6 interventions

Trial outcomes

Primary outcomes

1

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).

Time frame
Baseline
2

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).

Time frame
Baseline
3

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).

Time frame
Baseline
4

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).

Time frame
Baseline

Secondary outcomes

1

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.

Time frame
Baseline
2

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.

Time frame
Baseline

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

St. Jude Children's Research Hospital

Lead sponsor

Source ClinicalTrials.gov
Apply now