Ramipril Treatment of Claudication: Oxidative Damage and Muscle Fibrosis

NCT02842424 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: 0139-16-ET00991
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Peripheral artery disease (PAD) is a manifestation of atherosclerosis that produces progressive narrowing and occlusion of the arteries supplying the lower extremities. The most common clinical manifestation of PAD is claudication, i.e., a severe functional limitation identified as gait dysfunction and walking-induced leg muscle pain relieved by rest. The standard therapies for claudication include the medications cilostazol and pentoxifylline, supervised exercise therapy and operative revascularization. Recent data demonstrated that 24 weeks of treatment with the angiotensin-converting enzyme (ACE) inhibitor Ramipril produces improvements in the walking performance of patients with claudication that are higher than those of cilostazol and pentoxifylline and similar to those produced by supervised exercise therapy and operative revascularization. The mechanisms by which Ramipril therapy produces this impressive improvement in the functional capacity of claudicating patients remain unknown. The Investigators hypothesize that treatment of claudicating PAD patients with Ramipril will improve walking performance and quality of life by improving the myopathy of the gastrocnemius. Improved myopathy is a consequence of reduced oxidative damage, reduced TGF-β1 production by vascular smooth muscle cells and reduced collagen deposition in the affected gastrocnemius.

Conditions

Peripheral Arterial Disease

Keywords

Ramipril; Angiotensin-converting enzyme; Claudication; Myopathy; Peripheral Arterial Disease

Outcome Measures

Primary Outcomes (1)

• Absolute Claudication Distance

  Maximum walking distance in meters per Gardner protocol

  6 months

Secondary Outcomes (23)

• 6-minute Walking Distance

  6 months

• Initial Claudication Distance

  6 months

• Average Daily Steps Taken

  6 months

• Quality of life measured by the Walking Impairment Questionnaire

  6 months

• Quality of life measured by the Medical Outcomes Study Short Form 36 Healthy Survey

  6 months

Study Arms (1)

Ramipril Treatment

EXPERIMENTAL

6 months treatment with the medication Ramipril

Drug: Ramipril

Interventions

Ramipril DRUG

Ramipril therapy will start at 2.5mg/day for 1 week. Then 5mg/day for 1 week and will be increased to 10mg/day by the third week. The patients will stay on Ramipril 10mg/day for 22 weeks.

Also known as: Altace

Ramipril Treatment

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A positive history of chronic claudication,
• Exercise-limiting claudication established by history and direct observation during a screening walking test administered by the evaluating vascular surgeon,
• Arterial occlusive disease per ankle Brachial index measurements and/or other imaging modalities,
• Stable blood pressure regimen, stable lipid regimen, stable diabetes regimen and risk factor control for 6 weeks.

You may not qualify if:

• Rest pain or tissue loss due to PAD (Fontaine stage III and IV),
• acute lower extremity ischemic event secondary to thromboembolic disease or acute trauma,
• Walking capacity significantly limited by conditions other than claudication including leg (joint/musculoskeletal, neurologic) and systemic (heart, lung disease) pathology,
• Current use of either ACE inhibitors or angiotensin II receptor blockers,
• Chronic kidney disease with estimated Glomerular Filtration Rate \< 30 ml/min/1.73 m2,
• History of bilateral severe renal artery stenosis and 7) History of angioedema related to previous ACE-inhibitor treatment or known hypersensitivity to ramipril or other ACE inhibitors.

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

VA Medical Center

Omaha, Nebraska, 68105, United States

RECRUITING

MeSH Terms

Conditions

Peripheral Arterial Disease; Intermittent Claudication; Muscular Diseases

Interventions

Ramipril

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Iraklis I Pipinos, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

• George P Casale, PhD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Holly DeSpiegelaere

CONTACT

402-995-4171; Holly.DeSpiegelaere@va.gov

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2016
• First Posted: July 22, 2016
• Study Start: February 25, 2016
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: May 23, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)