Mitochondrial Function in Peripheral Arterial Disease

NCT ID: NCT05644158

Last Updated: 2024-03-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-01
• Study Completion Date: 2025-01-31

Brief Summary

The aim of this study is to investigate the effect of different treatment strategies on mitochondrial function and to correlate in-vitro results to findings from in-vivo measurements of mitochondrial function. The authors hypothesize that interventional revascularization and therefore the restoration of blood and oxygen supply is more relevant to mitochondrial function compared to the effect of exercise training.

Detailed Description

Resulting from a chronic narrowing of arteries by atherosclerotic lesions, the leading clinical symptom of peripheral arterial disease (PAD), a walking induced pain, reduces quality of life of patients. Affected muscle regions are altered by a characterized myopathy and mitochondria are known to play a crucial role in this pathophysiological mechanism. There are different methodological approaches to investigate mitochondrial function in-vivo as well as in-vitro. Regarding our own preliminary data, mitochondria are known to recover after successful revascularization. The effect of different treatment strategies on mitochondrial function and the correlation of in-vitro to clinical more applicable in-vivo methods was understudied so far.

The overall aim of this study is to investigate the effect of different treatment strategies on mitochondrial function and to correlate in-vitro results to findings from in-vivo measurements of mitochondrial function. The authors hypothesize that interventional revascularization and therefore the restoration of blood and oxygen supply is more relevant to mitochondrial function compared to the effect of exercise training.

Patients with isolated pathologies of the superficial femoral artery and symptomatic PAD (Fontaine stage IIB) will be included and randomized to different treatment groups (conservative treatment versus interventional revascularization). Near-infrared refracted spectroscopy and the TIVITA ® hyperspectral camera will be used for in-vivo measurement of peripheral oxygen saturation and distal perfusion before and after an exercise. Muscle biopsies will be obtained from affected (gastrocnemius muscle) as well as from unaffected muscle (lateral vastus muscle) shortly before and 12 weeks after initiating treatment. Muscle samples will be investigated by measurement of CSA regarding mitochondrial content and HRR regarding mitochondrial respiration as well as for oxidative stress.

Conditions

Peripheral Arterial Disease; Cardiovascular Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Exercise group

Patients with intermittent claudication will receive conservative treatment with monitored exercise training for a total of 12 weeks (home-based training, minimum of three times a week, documented by using a diary with documentation of the type, the intensity and the duration of the training as well as by using a physical activity monitoring system (Move 4, Karlsruhe, Germany).

Group Type: ACTIVE_COMPARATOR

Exercise therapy

Intervention Type: OTHER

Home-based monitored exercise training (walking), 3 times a week, monitored with log book and activity sensors.

Revascularization group

will receive revascularization of the underlying atherosclerosis lesion of the superficial femoral artery. Depending on the exact morphology of the lesion, patients with short superficial femoral artery lesions (\<25 cm) will be subdivided into group 2A with endovascular treatment and patients with long superficial femoral artery lesions (\>25 cm) will be subdivided into group 2B with open surgical treatment

Group Type: ACTIVE_COMPARATOR

Revascularization

Intervention Type: PROCEDURE

Depending on the exact morphology of the lesion, patients with short superficial femoral artery lesions (\<25 cm) will be subdivided into group 2A with endovascular treatment (percutaneous transluminal angioplasty with or without stenting) and patients with long superficial femoral artery lesions (\>25 cm) will be subdivided into group 2B with open surgical treatment (femoropopliteal bypass) .

Healthy control group

Patients undergoing surgery for symptomatic varicose veins with excluded PAD will serve as a control group.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Revascularization

Depending on the exact morphology of the lesion, patients with short superficial femoral artery lesions (\<25 cm) will be subdivided into group 2A with endovascular treatment (percutaneous transluminal angioplasty with or without stenting) and patients with long superficial femoral artery lesions (\>25 cm) will be subdivided into group 2B with open surgical treatment (femoropopliteal bypass) .

Intervention Type: PROCEDURE

Exercise therapy

Home-based monitored exercise training (walking), 3 times a week, monitored with log book and activity sensors.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Isolated flow limiting arteriosclerotic lesion of the superficial femoral artery
• Unilateral grade II b (Fontaine) peripheral arterial disease
• Informed consent

Exclusion Criteria

• Flow limiting arteriosclerotic lesions of the infrarenal aorta, iliac arteries or common/ deep femoral artery
• Contraindication for exercise therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University Innsbruck

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sabine Wipper, MD

Role: STUDY_CHAIR

Medical University of Innsbruck

Locations

Medical University Innsbruck

Innsbruck, Tyrol, Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Alexandra Gratl, MD

Role: CONTACT

alexandra.gratl@i-med.ac.at

00435050480804

Michaela Kluckner, MD

Role: CONTACT

michaela.kluckner@i-med.ac.at

00435050422587

Facility Contacts

Alexandra Gratl, MD

Role: primary

alexandra.gratl@i-med.ac.at

004350504 80804

References

Schoenherr L, Heidler J, Kluckner M, Lobenwein D, Pesta D, Frese JP, Wipper SH, Gratl A. A Randomized Control Trial Investigating the Effect of Different Treatment Strategies on Mitochondrial Function in Peripheral Arterial Disease: A Study Protocol. J Surg Res. 2025 Mar;307:78-85. doi: 10.1016/j.jss.2025.01.014. Epub 2025 Feb 22.

Reference Type: DERIVED

PMID: 39987612 (View on PubMed)

Other Identifiers

1194/2019

Identifier Type: -

Identifier Source: org_study_id