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

NCT ID: NCT01096121

Last Updated: 2012-07-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2012-06-30

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.

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.

Conditions

Sickle Cell Disease

Keywords

Angiotensin-converting enzyme inhibitors (ACE); Renal disease; Microalbuminemia

Study Design

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

Study Groups

2

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Glucose

1

Enalapril

Group Type: EXPERIMENTAL

Enalapril

Intervention Type: DRUG

• 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

Interventions

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

Intervention Type: DRUG

Placebo

Glucose

Intervention Type: DRUG

Other Intervention Names

Glucose

Eligibility Criteria

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 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

Tim ULINSKI, PH

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Trousseau Hospital, Nephro-pediatric unit

Paris, , France

Countries

France

References

Sasongko TH, Nagalla S. Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in people with sickle cell disease. Cochrane Database Syst Rev. 2021 Dec 21;12(12):CD009191. doi: 10.1002/14651858.CD009191.pub4.

Reference Type: DERIVED

PMID: 34932828 (View on PubMed)

Other Identifiers

AOM08052

Identifier Type: OTHER

Identifier Source: secondary_id

P071222

Identifier Type: -

Identifier Source: org_study_id