Spectroscopy in Functional Assessment of Peripheral Artery Disease (spectroAMI) (SPECTROAOMI)

Peripheral Artery Disease: Gated P-31 Magnetic Resonance Spectroscopy in Functional Assessment of Peripheral Artery Disease (spectroAMI)

To explore the reliability of P-31 MR spectroscopy mitochondrial function in patients with peripheral arterial occlusive disease.

Study Overview

• Status: Recruiting
• Conditions: Arterial Occlusive Diseases
• Intervention / Treatment: Device: Magnetic Resonance Imaging (MRI)

Detailed Description

Peripheral arterial occlusive disease (PAOD) is defined as the partial or total obstruction of one or more lower extremity arteries, most often of atherosclerotic origin. It is a common disease whose 5-years mortality is near 30%.The positive diagnosis is based on clinical examination and measurement of the ankle-brachial index (ABI), which is the ratio of systolic pressure of ankle and brachial systolic pressure. The threshold value for the diagnosis is <0.90. Physiopathologically, mitochondria have the predominant role of providing the ATP necessary for the energetic needs of myocytes, which increase drastically during muscle contraction during exercise. This energy production is of course conditioned by the availability of oxygen. In patients with PAOD, the decrease in blood flow secondary to significant stenosis has the direct consequence of disrupting oxygen delivery to distal muscles and thus limiting muscular performance. Because mitochondrial respiration is the only metabolic pathway capable of providing the energy needed to sustain an effort of several minutes, intermittent claudication in PAOD has logically been related to a hemodynamic mechanism of intermittent muscle hypoperfusion. Recently, an increasing number of histological or functional studies have suggested that episodes of ischemia-reperfusion could induce mitochondrial dysfunction. Medical treatment of patients frequently includes statins while a direct deleterious effect on mitochondrial function has been suspected, inducing a deterioration of the muscular oxidative capacity which would increase the factors hemodynamics and may accumulate in mitochondrial myopathy. In the light of these elements, it is clear that there would be a benefit in being able to distinguish and quantify 1) the part of the reduction of mitochondrial activity secondary to the hemodynamic factor alone due to a decreased muscle perfusion 2) the mitochondrial involvement (mitochondriopathy) potentially induced by oxidative stress in PAOD. 2 sub-groups are distinguished to identify the statin-induced mitochondrial dysfunction.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Pierre CROISILLE, PhD; Phone Number: +33 (0)477127584; Email: croisille@creatis.insa-lyon.fr

Study Locations

• France
  • Saint-Étienne, France
    • Recruiting
    • CHU Saint-Etienne
    • Sub-Investigator: Jean-Pierre FAVRE, PhD
    • Principal Investigator: Pierre CROISILLE, PhD
    • Sub-Investigator: Jean-Noël ALBERTINI, PhD
    • Sub-Investigator: Mourad BOUFI, PhD
    • Sub-Investigator: Aude GROGNET, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patient with Peripheral arterial occlusive disease with claudication and surgery planning

Description

Inclusion Criteria:

• Peripheral arterial occlusive disease (PAOD) with claudication and surgery planning with proximal lesion (iliac or femoral (x-ray angiography or CT or MRA) and no distal lesions (doppler)
• ABI<0.90 or >1.30
• signed consent form
• health insurance coverage

Exclusion Criteria:

• Contraindication in the practice of MRI: pacemaker, metallic cardiac valve, intra-ocular metal part, claustrophobia
• critical ischemia >15 days
• Type 1 or 2 diabetes
• weight >200kg
• non stabilized hypertension
• beta-blockers
• non-atherosclerotic vascular occlusive disease (Buerger disease, Takayasu disease, venous disease, trapped popliteal artery etc..)
• Neurological pathology/non-voluntary contraction

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PAOD patients statin (+); Patients with Peripheral Arterial Occlusive Disease (PAOD) and statin treatment. They will have Magnetic Resonance Imaging (MRI; muscular volume and composition) and gated-P-31 magnetic resonance spectroscopy (MRS) with low-intensity ergometric exercise. It will be performed before surgery (within 48h) and after surgery (first week)	Device: Magnetic Resonance Imaging (MRI); MRI (muscular volume and composition) and gated-P-31 magnetic resonance spectroscopy (MRS) with low-intensity ergometric exercise.
PAOD patients statin (-); Patients with Peripheral Arterial Occlusive Disease (PAOD) without statin treatment . They will have Magnetic Resonance Imaging (MRI ; muscular volume and composition) and gated-P-31 magnetic resonance spectroscopy (MRS) with low-intensity ergometric exercise. It will be performed before surgery (within 48h) and after surgery (first week)	Device: Magnetic Resonance Imaging (MRI); MRI (muscular volume and composition) and gated-P-31 magnetic resonance spectroscopy (MRS) with low-intensity ergometric exercise.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle phosphocreatine (PCr) recovery time constant	Muscle phosphocreatine (PCr) recovery time constant (index of muscle aerobic capacity) after gated low-intensity exercise (2"maximum voluntary isometric dorsiflexion contractions, at 30s intervals for 8min (total contractions = 15)	During the MRI procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscular volume and content	impact of muscular volume and content. Measures will be extracted from DIXON and T2* MRI	During the MRI procedure
PCr recovery time constant	impact of statin treatment on PCr recovery time constant	During the MRI procedure

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Dr MAYER Ronald A. Department of Physiology, Michigan State University; Dr SLADE Jill M. Department of Osteopathic Manipulative Medicine, Michigan State University
• Investigators: Principal Investigator: Pierre CROISILLE, PhD, CHU Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2019
• Primary Completion (Anticipated): April 1, 2025
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: October 26, 2018
• First Submitted That Met QC Criteria: October 26, 2018
• First Posted (Actual): October 29, 2018

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Revascularization; Spectroscopy; Magnetic Resonance Imaging (MRI); Peripheral Arterial Occlusive Disease (PAOD); Phosphorus-31; Claudication with surgical planning
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Atherosclerosis; Peripheral Vascular Diseases; Peripheral Arterial Disease; Arterial Occlusive Diseases
• Other Study ID Numbers: 1708029; 2017-A01421-52 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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