Mitochondrial Function in Peripheral Arterial Disease

Cardiovascular Diseases Clinical Trial

— MIVA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05644158
• Other study ID #: 1194/2019
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2022
• Est. completion date: January 31, 2025

Study information

• Verified date: March 2024
• Source: Medical University Innsbruck
• Contact: Alexandra Gratl, MD
• Phone: 00435050480804
• Email: alexandra.gratl[@]i-med.ac.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: January 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

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) .

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

Locations

Country	Name	City	State
Austria	Medical University Innsbruck	Innsbruck	Tyrol

Sponsors (1)

Lead Sponsor	Collaborator
Medical University Innsbruck

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in mitochondrial function after defined treatment	High-resolution respirometry of muscle biopsy sample	After 12 weeks - compared to baseline at inclusion
Primary	Change of near infrared spectroscopy	Near infrared spectroscopy measurement of calf	After 12 weeks - compared to baseline at inclusion
Secondary	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
Secondary	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
Secondary	Change in ankle-brachial index	Evaluation of hemodynamic parameters (ankle-brachial index).	After 12 weeks - compared to baseline at inclusion