Cyclosporine A in Patients With Small Diameter Abdominal Aortic Aneurysms

Small Abdominal Aortic Aneurysm Clinical Trial

— ACA4  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02225756
• Other study ID #: P110119
• Status: Recruiting
• Phase: Phase 2
• First received: August 6, 2014
• Last updated: June 1, 2015
• Start date: December 2013
• Est. completion date: September 2018

Study information

• Verified date: May 2015
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Eric Allaire, MD. PhD.
• Phone: (0)1 49 81 44 20
• Email: eric.allaire[@]hmn.aphp.fr
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 360
• Est. completion date: September 2018
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 85 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Abdominal Aortic Aneurysm,
• Aneurysm
• Aortic Aneurysm
• Aortic Aneurysm, Abdominal
• Small Abdominal Aortic Aneurysm

Intervention

Drug:
• Cyclosporine A
Oral administration for a short time of cyclosporine A dose 1
• Cyclosporine A
Oral administration for a short time of cyclosporine A dose 2
• Placebo
Oral administration for a short time of placebo

Locations

Country	Name	City	State
France	Henri Mondor Hospital	Créteil

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AAA diameter evolution on CT-scanner 12 months after treatment interruption		1 years	Yes
Secondary	AAA diameter evolution on duplex-scanner 12 months after treatment interruption		1 years	No
Secondary	Renal function (creatinine clearance)		at inclusion visit, V4 and V8	Yes
Secondary	All cause cardiovascular mortality and morbidity		at V1 and V8	No