Cyclosporine A in Patients With Small Diameter Abdominal Aortic Aneurysms

NCT ID: NCT02225756

Last Updated: 2015-06-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 360 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2018-09-30

Brief Summary

Aneurysms of the aorta are dilatations of the main artery in the body that distributes blood to organs. Aneurysms expose patients to aortic rupture. The risk of aortic rupture is high for large aneurysms, and low for small aneurysms. Currently, if the diameter of a small aneurysm grows up to a level at risk for rupture, surgery is indicated to prevent rupture. A drug that would stop growth of small aneurysms would obviate aortic surgery, the current treatment to prevent aortic rupture in patients. The ACA4 study aims at testing the possibility to stop growth of small aortic aneurysms in the abdomen with a drug, cyclosporine A. Patients with small aneurysms will receive cyclosporine A orally, or a placebo (fake liquid), every day during a short period of time. Efficacy of the drug will be evaluated by measuring the diameter of the aneurysm during 2 years after treatment cessation. Drug safety analysis will evaluate the impact of the drug on renal function, blood pressure, and other parameters. In case of adverse event during the drug administration phase, dose of the drug or of the placebo will be decreased or administration stopped.

Detailed Description

Abdominal aortic aneurysms (AAAs) expose patients to death caused by aortic rupture. Although screening of AAAs has been shown to decrease AAA-related mortality, translation into medical practice of screening is limited because there is no specific treatment to limit growth of AAAs below diameter thresholds for open surgery or stent graft. We have developed different approaches aimed at inducing healing and thereby stabilizing formed AAAs in animal models. We have identified TGF-beat1 as an inducer of experimental AAA healing. Cyclosporine A is an inducer of tumor growth factor - beta1 (TGF-beta1) in experimental AAAs and in human atherosclerotic AAAs in vitro, causing overgrowth of inflamed tissues. Since AAAs are caused by aortic wall atrophy, we have hypothesised and confirmed in animals, that cyclosporine AAA, when administrated during a short period of time, durably stabilizes small AAA diameter in animals, while inducing aortic wall reconstruction and healing.

The clinical trial ACA4 is a multicentric randomized, placebo controlled, double blind trial that will enrol 360 patients with small AAAs in France. Two doses of cyclosporine A will be tested against a placebo (three arms). Drug administration will be short, and AAA diameter evaluation will be performed for 2 years, by CT-scanner (main outcome) with no contrast, and duplex-scanner.

Conditions

Abdominal Aortic Aneurysm,; Small Abdominal Aortic Aneurysm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cyclosporine A dose 1

Group Type: EXPERIMENTAL

Cyclosporine A

Intervention Type: DRUG

Oral administration for a short time of cyclosporine A dose 1

Cyclosporine A dose 2

Group Type: EXPERIMENTAL

Cyclosporine A

Intervention Type: DRUG

Oral administration for a short time of cyclosporine A dose 2

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral administration for a short time of placebo

Interventions

Cyclosporine A

Oral administration for a short time of cyclosporine A dose 1

Intervention Type: DRUG

Cyclosporine A

Oral administration for a short time of cyclosporine A dose 2

Intervention Type: DRUG

Placebo

Oral administration for a short time of placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male patients with asymptomatic AAA ≥ 30 mm, ≤ 49 mm
• Female patients with asymptomatic AAA ≥ 25 mm, ≤ 44 mm

Exclusion Criteria

• Common iliac aneurysm > 25 mm
• Saccular aneurysm of the aorta
• Inflammatory aneurysm
• No signature of informed consent
• Renal dysfunction
• Diabetes

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric Allaire, MD. PhD.

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Henri Mondor Hospital

Créteil, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Eric Allaire, MD. PhD.

Role: CONTACT

eric.allaire@hmn.aphp.fr

(0)1 49 81 44 20 ext. +33

Morgane Quéré-Carne, CRA

Role: CONTACT

morgane.quere-carne@hmn.aphp.fr

(0)1 49 81 37 52 ext. +33

Facility Contacts

Marie-Antoinette Sevestre, MD, PhD

Role: primary

sevestre.marie-antoinette@chu-amiens.fr

(0)3 22 45 56 24 ext. +33

Patrick Lermusiaux, MD, PhD

Role: backup

patrick.lermusiaux@chu-lyon.fr

(0)4 72 11 76 76 ext. +33

Other Identifiers

P110119

Identifier Type: -

Identifier Source: org_study_id