Mitochondrial dysfUnction: a Key Player in Doxorubicin-induced Skeletal and Cardiac muscLE Damage

NCT05731375 | Unknown

• 1 other identifier: NL83538.041
• Study Type: observational
• Target: 12
• Locations: 1 country
• Sites: 2

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.

Conditions

Doxorubicin Induced Cardiomyopathy; Chemotherapeutic Toxicity; B-cell Lymphoma; T-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Changes in skeletal and cardiac muscle mitochondrial function

  Assessed through 31P-MRS imaging. Parameters include: * PCr recovery rate (in seconds) * PCr/ATP ratio

  Baseline, halfway (R-)CHOP treatment (+/- 9 weeks), after (R-)CHOP treatment (+/- 18 weeks)

Secondary Outcomes (12)

• Adherence rates to the study protocol

  Baseline to 18 weeks.

• Changes in physical fitness (Maximum short exercise capacity (Watt))

  Baseline, halfway (R-)CHOP treatment (+/- 9 weeks), after (R-)CHOP treatment (+/- 18 weeks)

• Changes in hand grip strength (kg)

  Baseline, halfway (R-)CHOP treatment (+/- 9 weeks), after (R-)CHOP treatment (+/- 18 weeks)

• Changes in leg strength (kg)

  Baseline, halfway (R-)CHOP treatment (+/- 9 weeks), after (R-)CHOP treatment (+/- 18 weeks)

• Changes in skeletal muscle area in cm2

  Baseline, halfway (R-)CHOP treatment (+/- 9 weeks), after (R-)CHOP treatment (+/- 18 weeks)

Other Outcomes (2)

• Changes in weight (kg)

  Baseline, halfway (R-)CHOP treatment (+/- 9 weeks), after (R-)CHOP treatment (+/- 18 weeks)

• Height (cm)

  Baseline, halfway (R-)CHOP treatment (+/- 9 weeks), after (R-)CHOP treatment (+/- 18 weeks)

Study Arms (1)

Study population

Patients with large B-cell lymphoma or T-cell lymphoma scheduled for 6 full-dose cycles of 1st line immunochemotherapy with (R-)CHOP

Diagnostic Test: 31-MRS at 7 Tesla (T)

Interventions

31-MRS at 7 Tesla (T) DIAGNOSTIC_TEST

31-MRS imaging at 7T to evaluate mitochondrial function in skeletal and cardiac muscles.

Study population

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited at UMC Utrecht, Diakonessenhuis Utrecht and possibly other hospitals in the vincity of the UMC Utrecht. The aim is to include 12 patients with large B-cell lymphoma or T-cell lymphoma, who are scheduled to undergo (R-)CHOP treatment at any of the recruiting hospitals.

You may qualify if:

• Age ≥ 18 years
• 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).
• WHO-performance score 0-2.
• Patients with sufficient Dutch writing and reading skills.
• Written informed consent.

You may not qualify if:

• Contra-indications for 7T MR scanning, including patients with a non-MRI compatible pacemaker, cochlear implant or neurostimulator; patients with non-MR compatible metallic implants in their eye, spine, thorax or abdomen; patients with a non-MR compatible aneurysm clip in their brain; patients with claustrophobia, and/or severe obesity.
• Any circumstances that would impede adherence to study requirements or ability to give informed consent.
• Medical disorders affecting mitochondrial function; e.g., spinal muscular atrophy.
• (Other) relevant medical disorders; e.g., comorbidities affecting exercise tolerance.
• Being under examination for non-diagnosed disease at the time of investigation.

Sponsors & Collaborators

• UMC Utrecht: lead
• Julius Clinical: collaborator

Study Sites (2)

Diakonessenhuis

Utrecht, 3582 KE, Netherlands

Location

UMC Utrecht

Utrecht, 3584CX, Netherlands

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, T-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

David Binyam, MD

CONTACT

+31648564688; d.binyam-2@umcutrecht.nl

Anouk Hiensch, PhD

CONTACT

+3188 75 677 08; a.e.hiensch@umcutrecht.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: January 25, 2023
• First Posted: February 16, 2023
• Study Start: April 1, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: February 16, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Data and documentation needed to reproduce findings from this study will be stored for at least 15 years.
• Access Criteria: Data access can only be granted for research with a research question in line with the original informed consent signed by the study participants.

Locations

NL (2)