Clinical trial NCT05644158: Mitochondrial Function in Peripheral Arterial Disease
Official title: Effect of Different Treatment Strategies on Mitochondrial Function in Peripheral Arterial Disease - a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Peripheral Arterial Disease
Cardiovascular Diseases
Keywords: mitochondrial function
respirometry
near infrared spectroscopy
endothelial dysfunction
peripheral arterial disease
exercise training
revascularisation
Lead sponsor: Medical University Innsbruck
Sponsor class: OTHER
First posted: 2022-12-09
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective randomized controlled trial

1. Exercise group
2. Revascularization group
3. Healthy control group
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Change in mitochondrial function after defined treatment
timeFrame: After 12 weeks - compared to baseline at inclusion
measure: Change of near infrared spectroscopy
timeFrame: After 12 weeks - compared to baseline at inclusion
Secondary outcomes:
measure: Change in flow mediated dilation of the brachial artery
timeFrame: After 12 weeks - compared to baseline at inclusion
measure: Change in standardized 6-minutes walking test
timeFrame: After 12 weeks - compared to baseline at inclusion
measure: Change in ankle-brachial index
timeFrame: After 12 weeks - compared to baseline at inclusion
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
state: Tyrol
Study officials:
affiliation: Medical University of Innsbruck
name: Sabine Wipper, MD
role: STUDY_CHAIR
References: