Mitochondrial Function in Peripheral Arterial Disease (MIVA)

Effect of Different Treatment Strategies on Mitochondrial Function in Peripheral Arterial Disease - a Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Peripheral Arterial Disease
• Intervention / Treatment: Other: Exercise therapy; Procedure: Revascularization

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 Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alexandra Gratl, MD; Phone Number: 00435050480804; Email: alexandra.gratl@i-med.ac.at
• Study Contact Backup: Name: Michaela Kluckner, MD; Phone Number: 00435050422587; Email: michaela.kluckner@i-med.ac.at

Study Locations

• Austria
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Recruiting
      • Medical University Innsbruck
      • Contact: Alexandra Gratl, MD; Phone Number: 004350504 80804; Email: alexandra.gratl@i-med.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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).	Other: Exercise therapy; Home-based monitored exercise training (walking), 3 times a week, monitored with log book and activity sensors.
Active Comparator: 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	Procedure: 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) .
No Intervention: Healthy control group; Patients undergoing surgery for symptomatic varicose veins with excluded PAD will serve as a control group.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Medical University Innsbruck
• Investigators: Study Chair: Sabine Wipper, MD, Medical University of Innsbruck

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: November 7, 2022
• First Submitted That Met QC Criteria: November 30, 2022
• First Posted (Actual): December 9, 2022

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: endothelial dysfunction; exercise training; peripheral arterial disease; near infrared spectroscopy; mitochondrial function; respirometry; revascularisation
• Additional Relevant MeSH Terms: Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Cardiovascular Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: 1194/2019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No