Cyclosporine A in Patients With Small Diameter Abdominal Aortic Aneurysms (ACA4)

Brief Administration of Cyclosporine A to Induce the Stabilisation of the Diameter of Small Diameter Abdominal Aortic Aneurysms.

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.

Study Overview

• Status: Unknown
• Conditions: Small Abdominal Aortic Aneurysm; Abdominal Aortic Aneurysm,
• Intervention / Treatment: Drug: Cyclosporine A; Drug: Cyclosporine A; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eric Allaire, MD. PhD.; Phone Number: +33 (0)1 49 81 44 20; Email: eric.allaire@hmn.aphp.fr
• Study Contact Backup: Name: Morgane Quéré-Carne, CRA; Phone Number: +33 (0)1 49 81 37 52; Email: morgane.quere-carne@hmn.aphp.fr

Study Locations

• France
  • Créteil, France, 94010
    • Recruiting
    • Henri Mondor Hospital
    • Contact: Marie-Antoinette Sevestre, MD, PhD; Phone Number: +33 (0)3 22 45 56 24; Email: sevestre.marie-antoinette@chu-amiens.fr
    • Contact: Patrick Lermusiaux, MD, PhD; Phone Number: +33 (0)4 72 11 76 76; Email: patrick.lermusiaux@chu-lyon.fr
    • Principal Investigator: Eric Allaire, MD. PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Oral administration for a short time of placebo
Experimental: Cyclosporine A dose 1	Drug: Cyclosporine A; Oral administration for a short time of cyclosporine A dose 1; Drug: Cyclosporine A; Oral administration for a short time of cyclosporine A dose 2
Experimental: Cyclosporine A dose 2	Drug: Cyclosporine A; Oral administration for a short time of cyclosporine A dose 1; Drug: Cyclosporine A; Oral administration for a short time of cyclosporine A dose 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AAA diameter evolution on CT-scanner 12 months after treatment interruption	1 years

Secondary Outcome Measures

Outcome Measure	Time Frame
AAA diameter evolution on duplex-scanner 12 months after treatment interruption	1 years
Renal function (creatinine clearance)	at inclusion visit, V4 and V8
All cause cardiovascular mortality and morbidity	at V1 and V8

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Eric Allaire, MD. PhD., Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Anticipated): September 1, 2017
• Study Completion (Anticipated): September 1, 2018

Study Registration Dates

• First Submitted: August 6, 2014
• First Submitted That Met QC Criteria: August 25, 2014
• First Posted (Estimate): August 26, 2014

Study Record Updates

• Last Update Posted (Estimate): June 3, 2015
• Last Update Submitted That Met QC Criteria: June 1, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Drug therapy; Therapy; Healing; Prevention and control; Tissue regeneration
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Aortic Diseases; Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: P110119