Clinical Trial: Dose-Dependent Effect of Thiazide in Dent's Disease Hypercalciuria
Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional
Official Title: Pharmacodynamic Evaluation of the ANTICALCIURIC Effect of Hydrochlorothiazide in Dent's Disease
Brief Summary: Intrarenal calcifications (nephrocalcinosis) is present in Dent's disease and likely contribute to progression toward renal failure. In order to prevent this complication it is usually proposed to treat affected patients during childhood with high doses of thiazides.
Detailed Summary:
Intrarenal calcifications (nephrocalcinosis) is present in Dent's disease and likely contribute to progression toward renal failure. In order to prevent this complication it is usually proposed to treat affected patients during childhood with high doses of thiazides. Indeed, this class of diuretics is used for years to treat hypertension, can lower urinary calcium excretion. However the doses usually used are high, are known to be associated with adverse events such as severe potassium depletion, decrease in blood pressure and dehydration. The purpose of the study was to test whether lower dose of thiazides would be better tolerated, with similar efficacy to lower urinary calcium excretion, as previously demonstrated in other indication such as treatment of hypertension.
Patient recruitment and clinical evaluation Eight subjects with genetically proven Dent's disease were recruited through a French nationwide network for tubulopathies and were enrolled between July 2003 and December 2005.
All patients met at least three standard criteria for the disease including hypercalciuria, low molecular weight proteinuria and one of the following disorders: nephrocalcinosis, nephrolithiasis, renal failure, aminoaciduria, glucosuria, renal phosphate wasting, or familial history of Dent's disease. The disease was confirmed in all patients by direct sequencing of the CLCN5 gene according to Lloyd et al. (25) Patients presenting hyponatremia (< 135 mM), hypokalaemia (< 3.3 mM), severe fanconi syndrome, or chronic renal failure (GFR estimated with the Schwartz formula < 30 mL.min-1.1.73m-2) were excluded from the study.
The protocol was approved by the "comité de protection des personnes" (Paris, Hôtel Dieu) and all subjects and/or their parents gave written in
Sponsor: Assistance Publique - Hôpitaux de Paris
Current Primary Outcome: to investigate the dose-dependent benefit/risk ratio of low (6.25 mg/day), intermediate (12.5 mg/day) and high (25 mg/day) doses of hydrochlorothiazide [ Time Frame: at the end of the baseline initial and final washout periods (one month each) and at the end of each two-months duration treatment period, ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- clinical events (cramps, symptomatic dehydration, acute weight loss) [ Time Frame: at least two times overall the study, at J15 and at the end of each period. ]
- Biological : acute renal failure (estimated GFR), hypokalemia, hyperkalemia, hyponatremia, biological signs of extra cellular dehydration (protides, hematocrit, plasma active renin, plasma aldosterone) [ Time Frame: at least two times overall the study, at J15 and at the end of each period. ]
Original Secondary Outcome: Same as current
Information By: Assistance Publique - Hôpitaux de Paris
Dates:
Date Received: March 12, 2008
Date Started: July 2003
Date Completion:
Last Updated: March 17, 2008
Last Verified: July 2003
