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

NCT05044611 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: APHP200042
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Bipolar Disorder

Keywords

lithium; urine concentration defect

Outcome Measures

Primary Outcomes (1)

• 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.

  The primary endpoint is the percentage change in maximal urine osmolality before and after 2 months of treatment

  2 month after randomization

Secondary Outcomes (11)

• Demonstrate the efficacy of amiloride to reduce nocturia

  2 months after randomization and 12 months after randomization

• Demonstrate the efficacy of amiloride to reduce the sensation of thirst

  2 months after randomization and 12 months after randomization

• Demonstrate the efficacy of amiloride to reduce polyuria

  2 months after randomization and 12 months after randomization

• Demonstrate the efficacy of amiloride to increase quality of life

  2 months after randomization and 12 months after randomization

• Demonstrate the efficacy of amiloride to reduce the decline of eGFR after one year of treatment

  12 months after randomization

Study Arms (2)

Amiloride

EXPERIMENTAL

the experimental arm will receive 5mg of amiloride twice daily during 2 months

Drug: Anhydrous Amiloride Hydrochloride

Placebo

PLACEBO COMPARATOR

the control arm will receive a placebo twice daily during 2 months

Drug: Placebo

Interventions

Anhydrous Amiloride Hydrochloride DRUG

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

Amiloride

Placebo DRUG

Route of administration : oral the control arm will receive a placebo twice daily during 2 months

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• Severe heart failure (NYHA \> II)
• 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)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Néphrologie, Hôpital Henri-Mondor

Créteil, France

Location

Physiologie Explorations fonctionnelles multidisciplinaires, Hôpital Bichat

Paris, France

Location

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Amiloride

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• DECHANET Aline, Mrs

  Assistance Publique - Hôpitaux de Paris (AP-HP)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two-phased study: 1st phase: Double blind, placebo-controlled, randomized trial to demonstrate the efficacy of 2 months treatment with amiloride 5mg twice a day to increase urine osmolality in patients with BD treated with lithium for at least 5 years and with a urine concentration defect. This double-blinded phase is followed by an open label phase (2nd phase) during 10 months to evaluate the long-term safety profile of the investigated drug and its potential nephroprotective role.

Study Record Dates

• First Submitted: August 27, 2021
• First Posted: September 16, 2021
• Study Start: January 11, 2023
• Primary Completion: March 3, 2025
• Study Completion: January 11, 2026
• Last Updated: May 9, 2025

Record last verified: 2025-05

Locations

FR (2)