Fluconazole in Hypercalciuric Patients With Increased 1,25(OH)2D Levels
Status:
Recruiting
Trial end date:
2023-07-13
Target enrollment:
Participant gender:
Summary
Hypercalciuria is one of the most frequent metabolic disorders associated with
nephrolithiasis and/or nephrocalcinosis leading to Chronic Kidney Disease (CKD) and bone
complications in adults.
Hypercalciuria can be secondary to increased intestinal absorption and/or increased renal
distal tubular reabsorption of calcium due to increased active vitamin D, i.e. 1,25(OH)2D,
levels. The management of hypercalciuria is challenging. Classic management based on
hyperhydration and dietary advice has low impact on calciuria and therefore on CKD
progression. Other strategies such as hydrochlorothiazide can be proposed, however with an
uncertain medical benefit in view of side effects (hypokalemia, asthenia, potential cutaneous
long-term side effects).
Azoles are known to inhibit the 1α-hydroxylase and therefore decrease 1,25(OH)2D levels.
These antifungal drugs are commonly used in neonates, infants and adults; pharmacokinetic
data are well described. Recently, to improve azoles tolerance, fluconazole has been
successfully reported to reduce calciuria in patients with CYP24A1 mutation (1 adult) or
NPTIIc mutations (1 child), while maintaining a stable renal function. Based on these
observations, the investigators hypothesize that fluconazole is effective to decrease and
normalize calciuria in patients with hypercalciuria and increased 1,25(OH)2D levels.
The primary objective is to demonstrate that fluconazole normalizes or decreases calciuria
after 4 months of treatment in patients with hypercalciuria and increased 1,25(OH)2D levels.
The secondary objectives aim to describe:
- the effects of fluconazole on the evolution over time of the calcium/phosphate
metabolism,
- the evolution of renal function,
- the cohort at Baseline and after 4 months of treatment period,
- the safety of fluconazole,
- the onset of potential mycological resistances,
- and the treatment compliance. This is a prospective, interventional, national,
randomized in 2 parallel groups (1:1), controlled versus placebo, double blind trial.
This study will involve patients between 10 and 50 years of age suffering from
nephrolithiasis and/or nephrocalcinosis with hypercalciuria (> 0.1 mmol/kg/d) and increased
1,25 (OH)2D levels (≥ 150 pmol/l) and 25-OH-D levels (≥50 nmol/L).
FLUCOLITH study is a unique opportunity to develop a new indication of a well-known and not
expensive drug (e.g. fluconazole) in rare renal diseases, the ultimate objective being the
secondary prevention of CKD worsening in these patients.
If the results of this proof-of-concept randomized controlled trial are positive, the
investigators will propose an extension phase to evaluate the long term efficacy and safety
of fluconazole on renal and bone parameters.