MADREPIEC: Angiotensin-converting Enzyme Inhibitors and Early Sickle Cell Renal Disease in Children

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Terminated

CT.gov ID

NCT01096121

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients with sickle cell anaemia may develop renal disease. In fact, renal disease occurred in 40% of adults patients (macroalbuminuria) with evolution to end-stage renal disease for half of them. Microalbuminuria is an early and sensitive marker of glomerular damage. It appears during the first decade and occurred in 20 to 25% of infants (2 to 18 years). Physiopathology of renal scarring is not well understood actually. Renal scarring might be due to glomerular hyperfiltration and vascular and endothelial damage. Angiotensin-converting enzyme inhibitors (ACE) were studied and used in diabetic nephropathy. In a study on 26 sickle cell adults, albuminuria was reduced about 50% by ACE compared to placebo after six months treatment. It might be interesting studying ACE efficacy in sickle cell children with microalbuminuria because renal disease is directly related to sickle cell and is not influenced by other cardiovascular risk factors like in adult patients.

We hypothesized to have a successful ACE treatment in more than 40% of cases after a nine months treatment period. A success is defined as a 50% reduction of the albuminuria/creatinuria ratio.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Drug: Enalapril Drug: Placebo	N/A

Detailed Description

This is a multicenter study. In order to include 72 patients we should pre-include 400 patients.

They will be included in the study after signing the protocol consent. For final inclusion in the study, two albuminuria/creatinuria ratio should be over or equal to 3mg/mmol. If so, inclusion will be done and patient will be randomized (placebo/enalapril) by CLEANWEB software. A blood sample will be done.

Treatment tolerance will be check up at day 7 (blood sample for renal tolerance and clinical examination), month 1(clinical examination), month 3(clinical examination), month 6(clinical examination), and month 9 (clinical examination). Treatment efficacy will be evaluated by albuminuria/creatinuria ratio at month 1, month 3, month 6, and month 9. Physiopathology of ACE efficacy will be studied at first day and month 9 by dosage of ICAM-1 and VCAM-1.

Treatment plain posology (0.5mg/kg/day) will be progressively obtained on a three months period, beginning at 0.2mg/kg/day.

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Interest of Angiotensin-converting Enzyme Inhibitors on Early Sickle Cell Renal Disease in Children. A Randomized, Double-blind Trial Enalapril vs Placebo.

Study Start Date :

Jun 1, 2010

Actual Primary Completion Date :

Jan 1, 2012

Actual Study Completion Date :

Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 2	Drug: Placebo Glucose Other Names: Glucose
Experimental: 1 Enalapril	Drug: Enalapril during 1 month : 0,2 mg/kg/day then during 2 months (if no adverse event): 0,35 mg/kg/day and then during 6 months (if no adverse event): 0,5 mg/kg/day

Arm

Intervention/Treatment

Placebo Comparator: 2

Drug: Placebo

Glucose

Other Names:

Glucose

Experimental: 1

Enalapril

Drug: Enalapril

during 1 month : 0,2 mg/kg/day then during 2 months (if no adverse event): 0,35 mg/kg/day and then during 6 months (if no adverse event): 0,5 mg/kg/day

Outcome Measures

Primary Outcome Measures

Percentage of successful treatment of each arm [at 9 months of treatment]
Successful treatment is defined by a reduction by half of the albuminuria/ creatinuria ratio (mg / mmol).

Secondary Outcome Measures

Measure of albuminuria/ creatinuria ratio [at 1, 3 and 6 month of treatment.]
Dosage of circulating forms of cell adhesion molecules ICAM-1 and VCAM-1 [at the first day and at 9 months of treatment.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Sickle cell disease (SS, SC, Sb thalassemia, SD Punjab)
Affiliation to French Health benefits
Signed informed consent
Albuminemia / Creatinemia >= 3 mg / mmol (on 2 samples)

Exclusion Criteria:

Albuminemia / Creatinemia > 100 mg / mmol
Hypersensibility to enalapril
Angio-oedemas due to a previous treatment by ACE
idiopathic or hereditary angio-oedemas
cerebral echo-doppler
treatment by lithium digoxine
treatment by other ACE
congenital galactosemia
Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Trousseau Hospital, Nephro-pediatric unit	Paris		France	75012

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Principal Investigator: Tim ULINSKI, PH, Assistance Publique - Hôpitaux de Paris

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Assistance Publique - Hôpitaux de Paris

ClinicalTrials.gov Identifier:

NCT01096121

Other Study ID Numbers:

P071222
AOM08052

First Posted:

Mar 30, 2010

Last Update Posted:

Jul 26, 2012

Last Verified:

Jun 1, 2012

Keywords provided by Assistance Publique - Hôpitaux de Paris

Angiotensin-converting enzyme inhibitors (ACE)

Renal disease

Microalbuminemia

Additional relevant MeSH terms:

Kidney Diseases

Anemia, Sickle Cell

Enalapril

Study Results

No Results Posted as of Jul 26, 2012