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

NCT01096121 | Terminated DMC

• 2 other identifiers: P071222AOM08052
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of successful treatment of each arm

  Successful treatment is defined by a reduction by half of the albuminuria/ creatinuria ratio (mg / mmol).

  at 9 months of treatment

Secondary Outcomes (2)

• 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.

Study Arms (2)

2

PLACEBO COMPARATOR

Drug: Placebo

1

EXPERIMENTAL

Enalapril

Drug: Enalapril

Interventions

Enalapril 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

1

Placebo DRUG

Glucose

Also known as: Glucose

2

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Trousseau Hospital, Nephro-pediatric unit

Paris, 75012, France

Location

Related Publications (1)

• 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.

  PMID: 34932828 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; Kidney Diseases

Interventions

Enalapril; Glucose

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Hexoses; Monosaccharides; Sugars; Carbohydrates

Study Officials

• Tim ULINSKI, PH

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2010
• First Posted: March 30, 2010
• Study Start: June 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: June 1, 2012
• Last Updated: July 26, 2012

Record last verified: 2012-06

Locations

FR (1)