AMIloride for the Treatment of Nephrogenic Diabetes Insipidus for Patients With Bipolar Disorder Treated With Lithium

• Status: Not yet recruiting
• Trial end date: 2024-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Amiloride

Criteria

Inclusion Criteria:

• Adults (age ≥ 18 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

• Hyperkalemia > 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)

• Acute phase of mood disorder

• Previous use of amiloride (long term use ≥ 6 months or/and 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