Mitochondrial Function in Peripheral Arterial Disease

Not Applicable

Recruiting

• Conditions: Peripheral Arterial Disease; Cardiovascular Diseases
• Interventions: Procedure: Revascularization; Other: Exercise therapy

• Registration Number: NCT05644158
• Lead Sponsor: Medical University Innsbruck

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.

Study Timeline

• Study Start: 2022-11-01
• Study First Submitted: 2022-11-07
• Study First Submitted QC: 2022-11-30
• Study First Posted: 2022-12-09
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-12
• Last Update Posted: 2024-03-13
• Primary Completion: 2024-12-31
• Study Completion: 2025-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Revascularization group	Revascularization	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
Exercise group	Exercise therapy	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).

Primary Outcome Measures

Name	Time	Method
Change of near infrared spectroscopy	After 12 weeks - compared to baseline at inclusion	Near infrared spectroscopy measurement of calf
Change in mitochondrial function after defined treatment	After 12 weeks - compared to baseline at inclusion	High-resolution respirometry of muscle biopsy sample

Secondary Outcome Measures

Name	Time	Method
Change in standardized 6-minutes walking test	After 12 weeks - compared to baseline at inclusion	Evaluation of cardiovascular risk with measurement of maximal walking distance (meters) in 6 minutes.
Change in ankle-brachial index	After 12 weeks - compared to baseline at inclusion	Evaluation of hemodynamic parameters (ankle-brachial index).
Change in flow mediated dilation of the brachial artery	After 12 weeks - compared to baseline at inclusion	Evaluation of endothelial dysfunction with ultrasound measurements of flow mediated dilation of the brachial artery.

Trial Locations

Locations (1)

Medical University Innsbruck; 🇦🇹 Innsbruck, Tyrol, Austria