Contact information
Type
Scientific
Primary contact
Dr F. Waanders
ORCID ID
Contact details
University Medical Center Groningen (UMCG)
Department of Nephrology
Hanzeplein 1
Groningen
9700 RB
Netherlands
+31 (0)50 3611564
F.Waanders@int.umcg.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
DUAAAL
Study hypothesis
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
Not provided at time of registration
Study design
Randomized, crossover, placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
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
Phase
Not Specified
Drug names
Lisinopril, valsartan
Primary outcome measures
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 trial start date
28/04/2006
Overall trial end date
01/09/2008
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
56
Participant 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
Recruitment start date
28/04/2006
Recruitment end date
01/09/2008
Locations
Countries of recruitment
Netherlands
Trial participating centre
University Medical Center Groningen (UMCG)
Groningen
9700 RB
Netherlands
Funders
Funder type
Industry
Funder name
Novartis Pharma B.V.
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary