The primary objective of this study is to determine the antialbuminuric response of vitamin D analogue in addition to ACE-inhibitor and low-sodium diet, in renal patients.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
chronische nierinsufficientie (excl. diabetische nefropathie)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Albuminuria (24-hour urinary albumin excretion)
Secondary outcome
- mean arterial pressure (MAP)
- serum creatinine / creatinine clearance
- PRA (plasma renin activity)
- renal hemodynamics (measured GFR, ERPF)
Background summary
Prevention of progressive renal function loss remains the main challenge in
clinical nephrology. Blockade of the renin-angiotensin-aldosterone system
(RAAS), which can be potentiated by a low-sodium diet, is the therapy of
choice, but still many patients develop end-stage renal disease on the long
term. Recent studies underline a crucial role for the vitamin D pathway in
progressive renal function loss, possibly due to interference in the RAAS. We
hypothesize that treatment with a vitamin D analogue could blunt the reactive
rise of renin levels seen in response to RAAS-blockade and reduce albuminuria,
thus optimizing renoprotection.
Study objective
The primary objective of this study is to determine the antialbuminuric
response of vitamin D analogue in addition to ACE-inhibitor and low-sodium
diet, in renal patients.
Study design
The study is designed as a multiple-center, double-blind, placebo-controlled,
crossover, randomized clinical trial.
Patients will enroll in a wash-out/wash-in period in which RAAS-blocking agents
and diuretics are discontinued, and 10 miligram ramipril 1dd1 is started.
Bloodpressure will be titrated to a value of <140/90 mmHg with additional
medication (in the fixed sequence of 100 miligram metoprolol retard 1dd1, 8
miligram doxazosin 1dd1, and 10 miligram amlodipine 1dd1), if needed.
Subsequently, patients will be consecutively treated in eight week treatment
periods, in randomized order, with placebo, the synthetic vitamin D receptor
acivator paricalcitol (1 microgram/day). At the same time, patients will be
randomly assigned to either a high-sodium diet (200 mmol Na/day) or a
low-sodium diet (50 mmol Na/day) during 32 weeks (two 16-week periods).
Every 8 weeks, after an overnight fast, patients will collect 24-h urine, BP is
measured, and blood is sampled to control dietary compliance and to monitor
renal function and BP. Also 24-h ambulatory blood pressure will be measured in
the centers that have the required devices available. In a subgroup of male
patients (those recruited in the UMCG and Martini Ziekenhuis), renal
hemodynamics (GFR/ERPF) will be measured. Every 4 weeks, 24-h urine is also
collected to control dietary compliance. Collected data at the end of each
eight week treatment period is used for analysis.
Intervention
paricalcitol 2 microgram / placebo
low-sodium diet / liberal-sodium diet
Study burden and risks
There are no direct benefits for the patients to be included. Participation in
the study is on a free-will base. Patients will not receive any financial
support or priority for treatment of other diseases in the clinic during this
study. Patients will visit the outpatient clinic on a more regular base than
standard patient care. During their visit, blood pressure, height and weight
will be measured. Also 24-h ambulatory blood pressure will be measured in the
centers that have the required devices available. Fasting blood samples will be
drawn during the venapuncture and 24-h urine will be collected. In a subgroup
of male patients (those recruited in the UMCG and Martini Ziekenhuis), renal
hemodynamics (GFR/ERPF) will be measured. The amount of radioactive radiation
during renal hemodynamic measurements is comparable to a single X-thorax (16%
of the yearly dosage of background radiation in the Netherlands). No further
invasive measurements will be executed and therefore risks of participation in
this study are minimal.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
- male and female patients
- non-diabetic renal disease as established by history, serum biochemistry tests and/or renal
biopsy
- age >=18 years
- residual albuminuria >300 mg/day and <10 g/day during conventional treatment of at least 8
weeks with ACE-inhibitor or ARB at the maximum recommended dose
- stable renal function (creatinine clearance of >30 ml/min/1.73m2; with <6 ml/min per year
decline)
- average of 2 consecutive PTH values of < 1.5 times the upper limit of normal (defined by the reference values of each participating center), 2 consecutive serum calcium levels
between 2.0 and 2.6 mmol/l (corrected for albumin levels), 2 consecutive serum phosphorus
levels of 1.5 mmol/l within 4 weeks prior to treatment
- written informed consent
Exclusion criteria
- uncontrolled hypertension, hyperkalemia (potassium >6.0 mmol/l, cardiovascular disease
(myocardial infarction, unstable angina, percutanous transluminal coronary angioplasty,
coronary artery bypass grafting, or stroke within last 6 months, heart failure NYHA III-IV),
Diabetes Mellitus
- epilepsy
- liver disease resulting in aberrations of liver function tests
- previously treated (within 3 months of screening) with paricalcitol or vitamin D (analogue)
- contraindication to ACEi, high/low-sodium diet or paricalcitol
- medication interacting with ACEi or paricalcitol
- frequent NSAID use (>2 doses/week)
- use of immunosuppressive drugs
- use of digoxine
- active malignancy
- any bowel disorder resulting in fat malabsorption
- pregnant or nursing (lactating) women, where pregnancy is defined as a state of a female after
conception and until the termination of gestation, confirmed by a positive ß-hCG laboratory test
(>5 mIU/ml).
- incompliance with diet or study medication
- any psychiatric condition or psychofarmacon use
- drug or alcohol abuse
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-016159-23-NL |
| Other | Nederlands Trial register: 9426 |
| CCMO | NL29900.042.09 |