AMIND - AMIloride for the treatment of Nephrogenic Diabetes insipidus for patients with bipolar disorder treated with lithium: a randomized controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

11 Jan 2023 → 5 Jan 2026

Decision date (initial)

2024-08-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

DGOS

External identifiers

EU CT number

2024-515018-42-00

EudraCT number

2021-003600-41

ClinicalTrials.gov

NCT05044611

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

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

Secondary objectives 7

1. The secondary objectives of the study are the following: Demonstrate the efficacy of amiloride to: Reduce the urine concentration defect
2. The secondary objectives of the study are the following: Demonstrate the efficacy of amiloride to reduce nocturia
3. The secondary objectives of the study are the following: Demonstrate the efficacy of amiloride to 3 reduce the sensation of thirst
4. The secondary objectives of the study are the following to reduce polyuria
5. Demonstrate the efficacy of amiloride to increase quality of life
6. Demonstrate the efficacy of amiloride to reduce the decline of eGFR after one year of treatment
7. Evaluate the effect of amiloride in 7. Mood stability 8. Circulating lithium levels stability 9. Demonstrate the tolerance of amiloride at short term after 2 months, and at long term (6 months and 12 months)

Conditions and MedDRA coding

Patients treated with lithium carbonate for a bipolar disorder treated for at least 5 years and with a urine concentration defect.

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. - Adults between 18 and 70 years (age ≥ 18 years and <70 years)
2. - Patient with bipolar disorder
3. - Patient treated with lithium for at least 5 years
4. - Patient with a urine concentration defect defined by a maximal urine osmolality < 600 mOsm/kg
5. - Woman of childbearing age agreeing to use an efficient contraceptive method for 12 months

Exclusion criteria 23

1. - Renal failure defined as eGFR < 30 ml/min/1.73m² estimated by the CKD-EPI equation
2. - Kalemia > 5 mmol/l
3. - Hypersensitivity or known allergy to amiloride
4. - Hypersensitivity to lactose
5. - Known adrenal insufficiency
6. - 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)
7. - Acute ongoing infection (less than 3 days before inclusion)
8. - Severe heart failure (NYHA > II)
9. - Rhythm, conduction or repolarisation disorder present on an ECG done within 12 months prior to inclusion
10. - Acute phase of mood disorder
11. - Uncontrolled diabetes mellitus or diabetes with hyporeninism hypoaldosteronism
12. - Use of potassium supplements
13. - Use of heparins
14. - Use of trimethoprim
15. - Cirrhosis
16. - Oedemas
17. - Previous use of amiloride use in the 6 months prior to randomisation)
18. - Pregnant or breastfeeding women
19. - Participation in another clinical study involving investigational medicinal product or patient being in the exclusion period at the end of a previous study
20. - Patient refusal to participate
21. - Non-affiliation to a social security regimen or CMU
22. - Patient under State Medical Aid
23. - Subject deprived of freedom, subject under a legal protective measure

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 10

1. Percentage change in maximal urine osmolality between baseline (before treatment) and at 6 and 12 months.
2. Self-declared mean number of nocturnal voids before treatment and at 2, 6 and 12 months.
3. Thirst intensity and distress scales score before treatment and at 2, 6 and 12 months.
4. Presence of polyuria (defined as a daily urine output > 3 L/day) after 2, 6, 12 months of treatment
5. Quality-of-life scale score (SF36) before treatment and at 2, 6 and 12 months.
6. eGFR (estimated by the CKD-EPI equation based on standardized serum creatinine measurement) before treatment and at 2, 6 and 12 months.
7. Mood Scale scores (YMRS and MADRS), anxiety scale score (GAD7) and the Pittsburgh sleep score (PSQI) before treatment and at 2, 6 and 12 months
8. Total number of hospital admission for maniac or depressive relapse during 12 months of treatment
9. Difference in residual plasma lithium levels before and after the 2 months treatment period
10. Short- and long-term tolerances evaluated via Common Terminology Criteria for Adverse Events (CTCAE) with an unacceptable toxicity defined as a grade >= 3 at 2, 6 and 12 months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Investigator

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Investigator

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications