AMIloride for the Treatment of Nephrogenic Diabetes Insipidus for Patients With Bipolar Disorder Treated With Lithium: a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 148
- 试验地点
- 2
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
Patients will be referred to the nephrology or the renal physiology department for the usual follow-up of the lithium treatment. After verification of eligilibity criteria, information and collection of consent, patient will be randomized.
During the first phase, patients will be randomized in two parallel groups: the experimental arm will receive 5mg of amiloride twice daily during 2 months and the control arm will receive a placebo twice daily during 2 months.
Measures of fasting urine osmolality will be performed at baseline, 2 months, at 6 months and at 12 months, in order to compare the difference of urine osmolality before and after treatment between the two-randomization arms. Other baseline explorations are as follows: mean number of nocturnal voids, SF-36 questionnaire, thirst intensity and distress scales, YMRS/MADRS mood scale, GAD7 anxiety scale, PSQI sleep scale, GFR measurement and estimation, 24h urine for the quantification of the polyuria and osmolality, plasma and erythrocyte lithium level, serum osmolality, natremia, kaliemia, urea, chlore level, complete blood count, plasma copeptine and vasopressin.
A nephrologist visit will take place 15 days after the initiation of the treatment along with a new measure of plasma lithium level.
Patients will be evaluated at 1 month only if a change in posology is required after the first measurement at day 15 and then at 2, 6 and 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
Amiloride
the experimental arm will receive 5mg of amiloride twice daily during 2 months
干预措施: Anhydrous Amiloride Hydrochloride (Drug)
Placebo
the control arm will receive a placebo twice daily during 2 months
干预措施: Placebo (Drug)
结局指标
主要结局
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.
时间窗: 2 month after randomization
The primary endpoint is the percentage change in maximal urine osmolality before and after 2 months of treatment
次要结局
- 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)
- Evaluate the effect of amiloride in mood stability(2 months after randomization and 12 months after randomization)
- Demonstrate the efficacy of amiloride to reduce nocturia(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)
- Evaluate the effect of amiloride in circulating lithium levels stability(2 months after randomization)
- Demonstrate the efficacy of amiloride to reduce the decline of eGFR after one year of treatment(12 months after randomization)