Ignite Creation Date:
2024-05-06 @ 6:39 PM
Last Modification Date:
2024-10-26 @ 2:51 PM
Study NCT ID:
NCT05731375
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-02-16
First Post:
2023-01-25
Brief Title:
Mitochondrial dysfUnction a Key Player in Doxorubicin-induced Skeletal and Cardiac muscLE Damage
Sponsor:
UMC Utrecht
Organization:
UMC Utrecht
Study Overview
Official Title:
Mitochondrial dysfUnction a Key Player in Doxorubicin-induced Skeletal and Cardiac muscLE Damage
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MUSCLE
Brief Summary:
The goal of this observational study is to demonstrate the ability of using non-invasive Phosphorus 31P Magnetic Resonance Spectroscopy MRS to monitor changes of in-vivo markers of mitochondrial function in skeletal and cardiac muscles in muscles in large B- or T-cell lymphoma patients during treatment with R-CHOP The main question it aims to answer is
Can 31P-MRS be used to monitor changes of in vivo markers of mitochondrial function in skeletal and cardiac muscles in large B- or T-cell lymphoma patients during treatment with R-CHOP
To be able to answer this main question participants will undergo 31P-MRS imaging of the calf muscles and of the heart 3 times during the study period
Can 31P-MRS be used to monitor changes of in vivo markers of mitochondrial function in skeletal and cardiac muscles in large B- or T-cell lymphoma patients during treatment with R-CHOP
To be able to answer this main question participants will undergo 31P-MRS imaging of the calf muscles and of the heart 3 times during the study period
Detailed Description:
Rationale Patients with large B-cell lymphoma or T-cell lymphoma are often treated with R-CHOP chemotherapy with the intent to cure the disease but this treatment can also lead to serious toxicities which may last for many years R-CHOP contains doxorubicin which has detrimental effects on skeletal and cardiac muscles Loss of skeletal muscle mass is associated with treatment modifications ie dose delayreductiondiscontinuation increased levels of fatigue decreased quality of life QoL and shorter survival Cardiomyopathy might lead to chronic heart failure in the long-term which negatively affects prognosis as well Preclinical studies investigating underlying mechanisms of these detrimental effects suggest that mitochondrial dysfunction plays a key role However human data is lacking due to the need of invasive repeated muscle biopsies Phosphorus 31P Magnetic Resonance Spectroscopy MRS is an innovative non-invasive technique which enables repeated measures of skeletal and cardiac muscle mitochondrial energy metabolism
Hypothesis
In this study the investigators hypothesize that patients with large B-cell lymphoma or T-cell lymphoma treated with R-CHOP will show decreased mitochondrial function in skeletal and cardiac muscle tissue following chemotherapy treatment
Objective
To demonstrate the ability of using non-invasive 31P-MRS to monitor changes of in vivo markers of mitochondrial function in skeletal and cardiac muscles ie skeletal muscle PCr recovery rate constant and cardiac PCrATP ratio in patients with large B-cell lymphoma or T-cell lymphoma during treatment with R-CHOP Furthermore the investigators will assess the feasibility of undergoing the study measurements for patients with large B-cell lymphoma or T-cell lymphoma during intensive R-CHOP treatment and explore the association between changes in in vivo measured mitochondrial function in skeletal and cardiac muscle tissue and changes in muscle mass physical fitness muscle strength physical activity levels measured by Fitbit chemotherapy completion rate and patient-reported outcomes including physical activity fatigue and quality of life
Study design Cohort study
Study population Patients with large B-cell lymphoma or T-cell lymphoma scheduled for 6 full-dose cycles of 1st line immunochemotherapy with cyclophosphamide doxorubicin vincristine and prednisone with or without rituximab reversed R-CHOP
Main study parametersendpoints
The main study parameters are differences in skeletal muscle PCr recovery rate constant and cardiac PCrATP ratio These parameters will be compared within-patients before halfway during and after completion of chemotherapy treatment
Nature and extent of the burden and risks associated with participation and benefit
Included patients will visit the UMC Utrecht 3 times ie before halfway during and after completion of chemotherapy treatment During these visits participants will undergo 31P-MRS imaging of the calf muscles and of the heart at 7 Tesla During the calf muscle scan patients will be asked to perform a mild exercise challenge ie dynamic plantar flexions 7T 31P-MRS is a safe and reliable technique for subjects without contra-indications for undergoing MRI Possible side-effects are limited to short-term vertigo and nausea In addition anthropometrics will be measured and small tests to evaluate muscle strength and physical performance will be performed Participants will be asked to complete questionnaires regarding physical activity quality of life and fatigue Finally patients will be asked to wear a Fitbit provided by the study team to objectively assess their levels of physical activity
Subjects will not experience direct benefits by participating in this study By the end of the study the investigators will demonstrate the ability to non-invasively monitor skeletal and cardiac muscle mitochondrial damage using 31P-MRS which is a pre-requisite to assess the efficacy of non-pharmacological interventions
Hypothesis
In this study the investigators hypothesize that patients with large B-cell lymphoma or T-cell lymphoma treated with R-CHOP will show decreased mitochondrial function in skeletal and cardiac muscle tissue following chemotherapy treatment
Objective
To demonstrate the ability of using non-invasive 31P-MRS to monitor changes of in vivo markers of mitochondrial function in skeletal and cardiac muscles ie skeletal muscle PCr recovery rate constant and cardiac PCrATP ratio in patients with large B-cell lymphoma or T-cell lymphoma during treatment with R-CHOP Furthermore the investigators will assess the feasibility of undergoing the study measurements for patients with large B-cell lymphoma or T-cell lymphoma during intensive R-CHOP treatment and explore the association between changes in in vivo measured mitochondrial function in skeletal and cardiac muscle tissue and changes in muscle mass physical fitness muscle strength physical activity levels measured by Fitbit chemotherapy completion rate and patient-reported outcomes including physical activity fatigue and quality of life
Study design Cohort study
Study population Patients with large B-cell lymphoma or T-cell lymphoma scheduled for 6 full-dose cycles of 1st line immunochemotherapy with cyclophosphamide doxorubicin vincristine and prednisone with or without rituximab reversed R-CHOP
Main study parametersendpoints
The main study parameters are differences in skeletal muscle PCr recovery rate constant and cardiac PCrATP ratio These parameters will be compared within-patients before halfway during and after completion of chemotherapy treatment
Nature and extent of the burden and risks associated with participation and benefit
Included patients will visit the UMC Utrecht 3 times ie before halfway during and after completion of chemotherapy treatment During these visits participants will undergo 31P-MRS imaging of the calf muscles and of the heart at 7 Tesla During the calf muscle scan patients will be asked to perform a mild exercise challenge ie dynamic plantar flexions 7T 31P-MRS is a safe and reliable technique for subjects without contra-indications for undergoing MRI Possible side-effects are limited to short-term vertigo and nausea In addition anthropometrics will be measured and small tests to evaluate muscle strength and physical performance will be performed Participants will be asked to complete questionnaires regarding physical activity quality of life and fatigue Finally patients will be asked to wear a Fitbit provided by the study team to objectively assess their levels of physical activity
Subjects will not experience direct benefits by participating in this study By the end of the study the investigators will demonstrate the ability to non-invasively monitor skeletal and cardiac muscle mitochondrial damage using 31P-MRS which is a pre-requisite to assess the efficacy of non-pharmacological interventions
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None