Dual renin-angiotensin system-blockade by angiotension-converting enzyme-inhibition and angiotension receptor type 1 receptor blockade, role of the angiotension-converting enzyme inhibitor or D genotype and low sodium diet in non-diabetic proteinuric patients
| ISRCTN | ISRCTN50137410 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN50137410 |
| Secondary identifying numbers | NL616, NTR675 |
- Submission date
- 29/06/2006
- Registration date
- 29/06/2006
- Last edited
- 08/01/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Urological and Genital Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr F. Waanders
Scientific
Scientific
University Medical Center Groningen (UMCG)
Department of Nephrology
Hanzeplein 1
Groningen
9700 RB
Netherlands
| Phone | +31 (0)50 3611564 |
|---|---|
| F.Waanders@int.umcg.nl |
Study information
| Study design | Randomized, crossover, placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | Dual renin-angiotensin system-blockade by angiotension-converting enzyme-inhibition and angiotension receptor type 1 receptor blockade, role of the angiotension-converting enzyme inhibitor or D genotype and low sodium diet in non-diabetic proteinuric patients |
| Study acronym | DUAAAL |
| Study objectives | The recently found gene-environment interaction between dietary sodium intake and the angiotensin-converting enzyme (ACE) genotype with sodium-induced therapy resistance to ACE inhibition in DD homozygotes (that was absent in II and ID subjects) is present in renal patients as well. With regards to the pathophysiological mechanism, we hypothesise that a high dietary sodium intake induces an increase in tissue ACE activity, which is stronger in the DD homozygotes, resulting in a worse therapy response to angiotensin-converting enzyme-inhibitors (ACEi). The alleged sodium-induced therapy resistance of the DD homozygotes may therefore be overcome by addition of angiotensin receptor type 1 (AT1) receptor blockade, since AT1 receptor blockers act downstream of the ACE. Moreover, we hypothesize that low dietary sodium intake has additional effects on proteinuria and blood pressure on top of dual renin-angiotensin system (RAS) blockade in patients with non-diabetic proteinuria |
| Ethics approval(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | Proteinuria |
| Intervention | Lisinopril 40 mg, with the addition of valsartan 320 mg (160 mg; twice a day) or placebo, both during low dietary sodium intake and high dietary sodium intake in randomised order |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Lisinopril, valsartan |
| Primary outcome measure | The primary endpoint will be reduction of proteinuria and blood pressure expressed as percentage change from baseline and analysed with each patient as his or her own control |
| Secondary outcome measures | 1. Serum creatinine 2. Circulating RAS parameters 3. Lipid profile 4. Adiponectin |
| Overall study start date | 28/04/2006 |
| Completion date | 01/09/2008 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 56 |
| Total final enrolment | 52 |
| Key inclusion criteria | 1. Older than 18 years of age 2. Chronic non-diabetic renal disease, as established by history, urine analysis, serum biochemistry tests and/or renal biopsy 3. Creatinine clearance >30 ml/min/1.73 m 4. Residual proteinuria >1 g per 24 hours |
| Key exclusion criteria | 1. Failure to meet the above inclusion criteria 2. Diabetes mellitus 3. Any contra-indication to the use of ACE inhibitors or AT1 receptor blockers 4. A history of myocardial infarction, unstable angina, coronary bypass or cardiovascular accident (CVA) during the past six months 5. Heart failure New York Heath Association (NYHA) class III-IV 6. High rate of renal function loss (decline in creatinine clearance >6 ml/min/1.73 m^2 during the past year) 7. Need for treatment with corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) or immunosuppressive drugs 8. Proteinuria >10 g per 24 hours and hypoalbuminaemia <28 g/l 9. Renovascular hypertension, malignant hypertension (diastolic blood pressure >100 mmHg) 10. Serum potassium >6 mmol/l |
| Date of first enrolment | 28/04/2006 |
| Date of final enrolment | 01/09/2008 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
University Medical Center Groningen (UMCG)
Groningen
9700 RB
Netherlands
9700 RB
Netherlands
Sponsor information
University Medical Center Groningen (UMCG) (The Netherlands)
University/education
University/education
P.O. Box 30001
Groningen
9700 RB
Netherlands
"ROR" |
https://ror.org/03cv38k47 |
|---|
Funders
Funder type
Industry
Novartis Pharma B.V.
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 26/07/2011 | 08/01/2021 | Yes | No |
Editorial Notes
08/01/2021: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
3. The NTR numbers have been added.
