Mannitol-induced Release of Copeptin in Healthy Adults and Patients With Polyuria-Polydipsia Syndrome: a Double-blind, Randomized Crossover Proof-of-concept and Open-label Single Arm Pilot Study (MARS Study)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- Difference in copeptin levels
研究概览
简要总结
The aims of this study are to investigate whether mannitol stimulates copeptin (part 1: proof-of-concept) and whether the copeptin levels upon mannitol infusion differ in primary polydipsia and arginine vasopressin deficiency (part 2: pilot study).
详细描述
Diagnosing polyuria-polydipsia syndrome, which includes arginine vasopressin (AVP) deficiency (AVP-D, formerly central diabetes insipidus) and primary polydipsia (PP), is challenging but essential. Currently, the most accurate test currently involves measuring copeptin after osmotic stimulation with hypertonic saline, but this test is rarely used due to the need for close sodium monitoring and the discomfort it can cause.
Mannitol has been shown to stimulate AVP release, but no study has tested copeptin levels after mannitol stimulation in healthy adults or patients with AVP-D or PP.
This single-center study is conducted in two consecutive parts. Part 1 is a double-blind, randomized cross-over proof-of-concept study in healthy adults to investigate if mannitol infusion stimulates copeptin release. Part 2 is an open-label, single arm case-control pilot study in adults with diagnosed PP or AVP-D to see if copeptin levels after mannitol stimulation differ in PP and AVP-D.
The results of this study aim to demonstrate if mannitol infusion has the potential to be used as an alternative to hypertonic saline infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
盲法说明
The study is conducted in two parts. Part 1: Double-blind Part 2: Open-label
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part 1: Proof of Concept in Healthy adults
- •Age ≥ 18 years
- •Healthy with no medication except hormonal contraception
- •Part 2: Pilot Study in Patients with primary polydipsia (PP) or arginine vasopressin deficiency (AVP-D)
- •Age ≥ 18 years
- •Evidence of polyuria > 40-50 ml/kg body weight per 24 hours and polydipsia > 3 Liter per 24 hours or regular desmopressin medication corresponding to a diagnosis of PP or AVP-D
排除标准
- •Part 1: Proof of Concept in Healthy adults
- •Participation in a trial with investigational drugs within 30 days
- •Evidence of disordered drinking habits and diuresis defined as polyuria > 40-50 ml/kg body weight per 24 hours and polydipsia > 3 Liter per 24 hours.
- •Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1,73 m2
- •Glucose > 11.1 mmol/L corresponding to the diagnosis of an uncontrolled diabetes mellitus
- •History of urinary tract obstruction
- •Problems with urination
- •Pregnancy or breastfeeding
- •Multiple allergies (≥ 3)
- •Evidence of acute illness
- •Part 2: Pilot Study in Patients with PP or AVP-D
- •Participation in a trial with investigational drugs within 30 days
- •Pregnancy or breastfeeding
- •Evidence of acute illness
- •eGFR < 60 ml/min/1,73 m2
- •Glucose > 11.1 mmol/L corresponding to the diagnosis of uncontrolled diabetes mellitus
- •History of urinary tract obstruction
- •Problems with urination
- •Therapy with diuretics
- •Multiple allergies (≥ 3)
结局指标
主要结局
Difference in copeptin levels
时间窗: Part 1: At 90 min post infusion, Part 2: at 30 min post infusion
The difference in copeptin levels at 90 minutes following a 30-minute infusion of mannitol, part 1: compared to placebo in healthy adults and part 2: between patients with (primary polydipsia) PP and arginine vasopressin deficiency (AVP-D)
次要结局
- Change of copeptin levels(Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes)
- Maximum copeptin levels(Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes)
- Assessment of hormone level(Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes)
- Assessment of serum electrolytes(Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes)
- Assessment of urea(Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes)
- Assessment of changes in ECG QTc Interval(Part 2: at Baseline and 90 min after infusion)
- Assessment of changes in ECG P- and T wave morphology(Part 2: at Baseline and 90 min after infusion)
- Assessment of plasma osmolality(Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes)
- Assessment of uric acid(Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes)
- Assessment of glucose(Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes)
- Assessment of urine parameters(Part 1: At baseline, 90 and 150 min after infusion, Part 2: At baseline, 30 and 90 min after infusion)
- Assessment of heart rate(Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes)
- Assessment of creatinine(Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes)
- Diagnostic accuracy of copeptin after mannitol Infusion for differentiating AVP-D from PP(Part 2: At 30 min post infusion)
- Assessment of changes in ECG Heart rate(Part 2: at Baseline and 90 min after infusion)
- Assessment of changes in ECG Cardiac rhythm(Part 2: at Baseline and 90 min after infusion)
- Assessment of changes in ECG QRS morphology(Part 2: at Baseline and 90 min after infusion)
- Assessment of blood pressure(Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes)
- Assessment of adverse effects(Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes)