Sickle Cell DiseaseMADREPIECNCT01096121
Angiotensin-converting Enzyme Inhibitors and Early Sickle Cell Renal Disease in Children
A study testing Enalapril in people with Sickle Cell Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Enalapril
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2010to Jun 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 9Show fewer
- treatment by other ACE
- congenital galactosemia
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Interest of Angiotensin-converting Enzyme Inhibitors on Early Sickle Cell Renal Disease in Children. A Randomized, Double-blind Trial Enalapril vs Placebo.
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.
Read the 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
- Being tested
- Enalapril, Placebo
- Keywords
- Angiotensin-converting enzyme inhibitors (ACE), Renal disease, Microalbuminemia
- Medical subject headings
- Anemia, Sickle Cell, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnalaprilDrug
- 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
PlaceboDrug
Also called Glucose
Glucose
| Study group | Role | What they receive |
|---|---|---|
| 2 | Placebo comparator | Not described Receives: Drug: Placebo |
| 1 | Experimental | Enalapril Receives: Drug: Enalapril |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of successful treatment of each arm
Successful treatment is defined by a reduction by half of the albuminuria/ creatinuria ratio (mg / mmol).
Measured: at 9 months of treatment
Secondary outcomes (2)
Measure of albuminuria/ creatinuria ratio
Measured: at 1, 3 and 6 month of treatment.
Dosage of circulating forms of cell adhesion molecules ICAM-1 and VCAM-1
Measured: at the first day and at 9 months of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2010 (estimated)
- Study startJun 2010
- Primary completionJan 2012
- Study completionJun 2012
Why it stopped: Not enough inclusions
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tim ULINSKI, PH, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01096121
- Sponsor's protocol ID
- P071222
- Other IDs
- AOM08052
- Acronym
- MADREPIEC
- Status last verified
- Jun 2012
- First submitted
- 29 Mar 2010
- Last updated
- 26 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 34932828
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interest of Angiotensin-converting Enzyme Inhibitors on Early Sickle Cell Renal Disease in Children. A Randomized, Double-blind Trial Enalapril vs Placebo.
- ClinicalTrials.gov ID
- NCT01096121
- Acronym / sponsor ID
- MADREPIEC / P071222
- Conditions
- Sickle Cell Disease
- Keywords
- Angiotensin-converting enzyme inhibitors (ACE), Renal disease, Microalbuminemia
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Not enough inclusions
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jun 2010
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 30 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2 | Placebo comparator | Drug: Placebo |
| 1 | Experimental | Drug: EnalaprilEnalapril |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Drug | 1 |
| PlaceboAlso: GlucoseGlucose | Drug | 2 |
Primary outcome
Percentage of successful treatment of each arm
Time frame: at 9 months of treatment
Successful treatment is defined by a reduction by half of the albuminuria/ creatinuria ratio (mg / mmol).
2 secondary outcomes
Measure of albuminuria/ creatinuria ratio
Time frame: at 1, 3 and 6 month of treatment.
Dosage of circulating forms of cell adhesion molecules ICAM-1 and VCAM-1
Time frame: at the first day and at 9 months of treatment.
Results and safety
The study was stopped early (reason given: Not enough inclusions). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2012.
- Derived from this study: PubMed 34932828Sasongko 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tim ULINSKI, PH principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Enalapril in people with Sickle Cell Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Not enough inclusions). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of successful treatment of each arm (time frame: at 9 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01096121, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2012.