Anhydrous Amiloride Hydrochloride: Amiloride is a blocker of ENaC that is administered patients with various disorders, such as primary or secondary hyperaldosteronism. It does not have the market authorization in the indication of lithium-induced NDI.
Dose : 5 mg Pharmaceutical form: Tablets Daily Posology : 10 mg Route of administration : oral Procedures and duration of treatment: 2 months during the double blinded phase and 10 additional months for the open label phase
Placebo: Route of administration : oral the control arm will receive a placebo twice daily during 2 months
Study summary
Lithium (Li) is the leading treatment for BD, protecting against both maniac and depressive relapse, and reducing the risk of suicide and mortality. However, despite this major clinical efficacy, the use of lithium is limited by its narrow therapeutic index and by its side effects. Li induces a vasopressin-resistant urinary concentration defect, with resulting nephrogenic diabetes insipidus (NDI) in 12-50 % of patients. This feature is more frequent after 5 years of treatment with lithium. Polyuria and subsequent thirst might affect patients' quality of life, but also cause potentially life-threatening hypernatremia if free access to water is impaired. Thus, we aim at evaluating the efficacy of amiloride on urine concentrating ability in patients with nephrogenic diabetes insipidus due to chronic lithium treatment.
Eligibility
Sex
ALL
Min age
18 Years
Max age
70 Years
Healthy volunteers
No
Inclusion Criteria:
* Adults between 18 and 70 years (age ≥ 18 years and \<70 years)
* Patient with bipolar disorder
* Patient treated with lithium for at least 5 years
* Patient with a urine concentration defect defined by a maximal urine osmolality \< 600 mOsm/kg
* Woman of childbearing age agreeing to use an efficient contraceptive method for 12 months
Exclusion Criteria:
* Renal failure defined as eGFR \< 30 ml/min/1.73m² estimated by the CKD-EPI equation
* Kalemia \> 5 mmol/l
* Hypersensitivity or known allergy to amiloride
* Hypersensitivity to lactose
* Known adrenal insufficiency
* Concomitant use of other potassium-sparing treatment (e.g. spironolactone, angiotensin converting enzyme inhibitors (ACE), angiotensin II receptor (AT2R) antagonists, calcineurin inhibitors tacrolimus and ciclosporin)
* Acute ongoing infection (less than 3 days before inclusion)
* Severe heart failure (NYHA \> II)
* Rhythm, conduction or repolarisation disorder present on an ECG done within 12 months prior to inclusion
* Acute phase of mood disorder
* Uncontrolled diabetes mellitus or diabetes with hyporeninism hypoaldosteronism
* Potassium supplements
* Use of heparins
* Use of trimethoprim
* Cirrhosis
* Oedemas
* Previous use of amiloride use in the 6 months prior to randomisation)
* Pregnant or breastfeeding women
* Participation in another clinical study involving investigational medicinal product or patient being in the exclusion period at the end of a previous study
* Patient refusal to participate
* Non-affiliation to a social security regimen or CMU
* Patient under State Medical Aid
* Subject deprived of freedom, subject under a legal protective measure
Primary outcome measure(s)
The main objective of this study is demonstrating the efficacy of amiloride to reduce the urine concentration defect in patients treated by lithium and presenting a nephrogenic diabetes insipidus after 2 months of treatment. — 2 month after randomization The primary endpoint is the percentage change in maximal urine osmolality before and after 2 months of treatment
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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