Effect and Safety MABs Administration m.3243A>G Mutation Carriers

NCT ID: NCT05962333

Last Updated: 2024-04-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-01
• Study Completion Date: 2025-02-01

Brief Summary

The first primary objective is to assess the effect of three intra-arterial administrations of autologous mesoangioblasts (MABs) with respect to improving muscle strength and reduce fatigue of the treated biceps brachii (BB) compared to the untreated BB.

The second primary objective is safety of three intra-arterial administrations of autologous MABs, which the investigators will assess by monitoring (serious) adverse events ((S)AEs), blood flow in left arm pre- and post-intervention, and neurological vital signs during 8h post-intervention observation in the hospital.

Secondary objectives are to assess changes in muscle mass of the treated and untreated BB muscle, and microscopic changes and m.3243A>G mutation load at tissue level in treated biceps brachii (BB) muscle at baseline and after treatment.

Up to 20 adult m.3243A>G patients will undergo a ~30mg m. biceps brachii muscle biopsy at visit 1. The first six eligible patients will enroll the clinical study based on their m.3243A>G mutation load in skeletal muscle (50-90%) and mesoangioblasts (<10%), and on a decreased BB muscle strength and increased fatigue.

These 6 selected patients will visit the Maastricht University Medical Center for 8 additional times. From each patient, during visit 2 till 9:

• BB muscle biopsies of the left arm will be collected (1x ~130 mg at visit 2 and 1x ~30mg at visit 9)
• MRI of the BB muscles in both arms will be performed (visit 2 and 9).
• Autologous MABs will be injected into the left arm via axillary artery delivery. Angiography will be performed before and after infusion to assess vascular obstructions, and the participant will be monitored in the hospital for 8 hours (visit 4,6,8).
• Tc99m macroaggregated albumin (MAA) is infused to quantify blood flow to the BB muscle (visit 4).
• A bout of maximal eccentric exercise of BB muscles on both sides will be executed at visit 3, 5 and 7.
• BB muscle strength will be assessed using a Biodex dynamometer (visit 3-9)
• venous blood samples will be taken for assessing muscle damage and inflammation markers (visit 3-9), kidney functioning, coagulation and viral screening (visit 1 and 2).

Conditions

Mitochondrial Myopathies

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intra-arterial delivery of autologous MABs

Autologous MABs will be injected three times in left arm to treat biceps brachii muscle

Group Type: EXPERIMENTAL

Intra-arterial delivery of autologous MABs

Intervention Type: BIOLOGICAL

three times intra-arterial administration of autologous mesoangioblasts in biceps brachii of the left arm at 4-6 week interval

Interventions

Intra-arterial delivery of autologous MABs

three times intra-arterial administration of autologous mesoangioblasts in biceps brachii of the left arm at 4-6 week interval

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Written informed consent
• Age: 18-64
• Sex: male/female
• Patients with the m.3243A>G mutation load of 50%-90% determined in skeletal muscle or derived from age-corrected calculation of blood m.3243A>G mutation load

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• Use of dabigatran, apixaban, edoxaban or rivaroxaban (DOACs) as anti-coagulants
• Have a weekly alcohol intake of ≥ 35 units (men) or ≥ 24 units (women)
• Current history of drug abuse
• Deficient immune system or autoimmune disease
• Significant concurrent illness
• Ongoing participation in other clinical trials with intervention
• Pregnant or lactating women
• Psychiatric or other disorders likely to impact on informed consent
• Patients unable and/or unwilling to comply with treatment and study instructions
• A history of strokes with signs of extra-pyramidal or pyramidal syndrome
• Allergy for contrast fluid
• Peripheral signs of ischemia or vasculopathy
• Claustrophobia
• Metal implants
• Any other factor that in the opinion of the investigator excludes the patient from the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maastricht University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janneke Hoeijmakers, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Center

Locations

Maastricht University Medical Center

Maastricht, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Florence van Tienen, PhD

Role: CONTACT

florence.vantienen@maastrichtuniversity.nl

00314331995

Bert Smeets, Prof. PhD

Role: CONTACT

bert.smeets@maastrichtuniversity.nl

00314331995

Facility Contacts

Florence van Tienen, PhD

Role: primary

0031433882918

References

van Tienen F, Zelissen R, Timmer E, van Gisbergen M, Lindsey P, Quattrocelli M, Sampaolesi M, Mulder-den Hartog E, de Coo I, Smeets H. Healthy, mtDNA-mutation free mesoangioblasts from mtDNA patients qualify for autologous therapy. Stem Cell Res Ther. 2019 Dec 21;10(1):405. doi: 10.1186/s13287-019-1510-8.

Reference Type: RESULT

PMID: 31864395 (View on PubMed)

Related Links

http://www.generateyourmuscle.com

website Generate Your Muscle (GYM) project

Other Identifiers

NL82815.000.22

Identifier Type: -

Identifier Source: org_study_id