A Phase 2 interventional study of Fluconazole and Placebo in Nephrolithiasis, Nephrocalcinosis and Hypercalciuria, sponsored by Hospices Civils de Lyon. Completed at 11 sites in France. Open to participants aged 10 Years to 60 Years. Per ClinicalTrials.gov, last updated 2024-07-12.
Sponsored by Hospices Civils de Lyon · Phase 2, Interventional, and Treatment
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 18 weeks of treatment in patients with hypercalciuria and increased 1,25(OH)2D levels.
The secondary objectives aim to describe:
This study will involve patients between 10 and 60 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.
324 studies on the registry are indexed under Nephrolithiasis; 90 are open to participants now.
This study's enrollment of 56 is below the median of 92 across 257 interventional studies indexed under Nephrolithiasis.
Browse Nephrolithiasis studies →Hospices Civils de Lyon is the lead sponsor of 1,866 studies on the registry; 448 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients who have at inclusion (V1), a local biological evaluation with:
Exclusion Criteria:
Relating to the risk of QT interval prolongation:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Fluconazole 50mg capsule (1, 2, 3 or 4 pills to take daily during 18 weeks, corresponding respectively to 50, 100, 150 or 200 mg of fluconazole).
Drug: Fluconazole
Placebo (1, 2, 3 or 4 pills to take daily during 18 weeks), same appearance to experimental drug
Drug: Placebo
Fluconazole 50 mg/capsule or placebo, per os during 18 weeks : * From W0 to W2 : 1 caps/ day * From W2 to W4 : 1 or 2 caps/day * From W4 to W6 : 1, 2 or 3 caps/day * From W6 to W18 : 1, 2, 3 or 4 caps/day The number of capsules to take will be determined by 24-hours calciuria results performed every 2 weeks during the titration period (W2, W4 and W6). During the titration period, if 24-hours calciuria is \> 0.1 mmol/kg/day, fluconazole dose will be increased every 2 weeks to 50 mg per intake, with a maximum dose of 200 mg/day. If 24-hour calciuria is ≤ 0.1mmol/kg/day, fluconazole dose will remain stable. After W6 and until the end of the study, the treatment dose will remain stable (stable period).
Placebo (1, 2, 3 or 4 pills to take daily during 18 weeks), same appearance to experimental drug
Proportion of patients with normalization of calciuria
Proportion of patients with normalization of 24-hour calciuria (≤ 0.1 mmol/kg/d) between Baseline (V1) and W18 (V7), or with a relative change of 30% of 24-hour calciuria between Baseline (V1) and W18 (V7) for patients who still have at W18 a 24-hour calciuria\> 0.1mmol/kg/d.
Time frame: Baseline (V1) and 18 weeks of treatment (V7)
Evolution over time of the calcium/phosphate metabolism (serum and urines dosages)
Serum: calcium, ionized calcium, phosphate, magnesium, PTH, 25-OH-D, 1,25(OH)2D, 24-25 (OH)2 D, 25-OH-D:24-25(OH)2D ratio, total alkaline phosphatase.
Time frame: Baseline (V1), 18 weeks of treatment (V7)
Serum creatinine
Evolution of renal function
Time frame: Baseline (V1), 18 weeks of treatment (V7)
number of lithiasis, nephrocalcinosis
Evolution of renal function
Time frame: Baseline (V1), 18 weeks of treatment (V7)
size of lithiasis, nephrocalcinosis
Evolution of renal function
Time frame: Baseline (V1), 18 weeks of treatment (V7)
Quantity of calcium intakes
Anthropometry
Time frame: 18 weeks
Quantity of sodium intakes
Anthropometry
Time frame: 18 weeks
Quantity of protein intakes
Anthropometry
Time frame: 18 weeks
bone alkaline phosphatases
Bone evaluation with biomarkers
Time frame: 16 weeks
FGF23
Bone evaluation with biomarkers
Time frame: 16 weeks
Klotho
Bone evaluation with biomarkers
Time frame: 18 weeks
femoral neck (FN) assessed with Dual energy x-ray absorptiometry (DXA):
Bone evaluation with biomarkers
Time frame: at randomization (day 0)
lumbar spine vertebra 2 to 4 (LS2-4) areal bone mineral density assessed with Dual energy x-ray absorptiometry (DXA):
Bone evaluation with biomarkers
Time frame: at randomization (day 0)
total body (TB) areal bone mineral density assessed with Dual energy x-ray absorptiometry (DXA):
Bone evaluation with biomarkers
Time frame: at randomization (day 0)
Safety evaluation through the study : cardiac evaluation
Cardiac evaluation : electrocardiogram, corrected QT interval
Time frame: Baseline (V1)
Safety evaluation through the study : cardiac evaluation
Cardiac evaluation : electrocardiogram, corrected QT interval
Time frame: 4 weeks
Safety evaluation through the study : cardiac evaluation
Cardiac evaluation : electrocardiogram, corrected QT interval
Time frame: 10 weeks
Safety evaluation through the study : blood analysis
Hepatic functions : aspartate transaminase
Time frame: 20 weeks
Safety evaluation through the study : blood analysis
Hepatic functions : bilirubin
Time frame: 20 weeks
Safety evaluation through the study : blood analysis
Hepatic functions : gamma-glutamyl-transpeptidase
Time frame: 20 weeks
Safety evaluation through the study : blood analysis
Lactate dehydrogenase
Time frame: 20 weeks
Safety evaluation through the study : blood analysis
phosphoremia
Time frame: 20 weeks
Safety evaluation through the study : blood analysis
Calcemia
Time frame: 20 weeks
Safety evaluation through the study : blood analysis
Serum creatinine
Time frame: 20 weeks
Safety evaluation through the study : blood analysis
Albumin
Time frame: 20 weeks
Safety evaluation through the study : blood analysis
Hepatic functions : alanine aminotransferase
Time frame: 18 weeks
Safety evaluation through the study : blood analysis
Complete blood cell counts
Time frame: 20 weeks
Proportion of patients that developed mycological resistance
Mycological urine samples will be collected to evaluate the onset of potential mycological resistances to Candida. A description of the proportion of patients that developed at least one mycological resistance into the study will be performed by treatment arm, with a listing of the given resistances.
Time frame: 18 weeks
Proportion of patients that developed mycological resistance
Mycological buccal samples will be collected to evaluate the onset of potential mycological resistances to Candida. A description of the proportion of patients that developed at least one mycological resistance into the study will be performed by treatment arm, with a listing of the given resistances.
Time frame: 18 weeks
Compliance assessment
Compliance under treatment (fluconazole or placebo) will be measured by accountability of returned study treatment and information recorded on patients' diary. Level of compliance will be described separately at several follow-up times
Time frame: every month from Randomization (V2) to 18 weeks of treatment (V7)
Quality of life and treatment satisfaction assessments : adults
Quality of life will be assessed with SF-36 auto-questionnaire (for adult patients)
Time frame: The endpoint will be the variation of total score between Randomization (V2) and 18 weeks of treatment (V7)
Quality of life and treatment satisfaction assessments : children and adolescents
PedsQL auto-questionnaire (PedsQL 8-12 years for children, and PedsQL 13-18 years for adolescents).
Time frame: The endpoint will be the variation of total score between Randomization (V2) and 18 weeks of treatment (V7)
Ran from Jan 2021 to primary completion in Jul 2024, 41 months.
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Studies of the drug tested here: Fluconazole