Monocentric STUDY, Randomised Double Blinded (Healthy Subjects, or Transversal (Patients With Gitelman Syndrome)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Effect of potassium depletion on plasma progesterone (Change from Baseline of progesterone)
研究概览
简要总结
Progesterone is needed to permit adaptation of the kidney to limit potassium loss in the urines. The investigators wonder whether progesterone or other adrenal hormon play the same role. The investigators will investigate surrenal hormone production in healthy subjects under a 7-day potassium depleted diet and in patients chronically hypokalaemic due to a renal loss of potassium.
详细描述
The investigators will study the adaptation of steroidogenesis to potassium depletion in healthy volunteer, and the role of progesterone in renal adaptation to potassium depletion. Practically, healthy volunteers will be submitted twice to two periods of normal Na+/ high K+ diet (control period) followed by a normal Na+/ low K+ diet sustained by a pharmacological treatment with Kayexalate (K+-depleted condition). The subjects will be treated with either RU486 or a placebo, according to a randomization. The adrenal response will be evaluated after stimulation by Synacthen at baseline and at the end of each experimental period. A Synacthen test will be also done in 10 patients suffering of chronic hypokalemia linked to a hereditary tubulopathy inducing renal K+ leak called Gitelman syndrome and their plasma steroid profile will be established.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •for healthy subjects:
- •Caucasian male subject
- •18-35 yrs-old
- •BMI between 18 and 30 Kg/m2
- •Normal biological pattern (sodium, potassium, eGFR >60mL/min/1.73 m2, SGOT and SGPT < 2.5 normal value)
- •Non smoker subjects or less than 5 cigarettes a day
- •No drug abuse
- •No active viral B or C hepatitis, no positive HIV serology
- •No treatment except paracetamol
- •Normal EKG
- •Inform consent given
- •Affiliation to French Medicare assurance
- •Inclusion Criteria for patients :
- •18-75 Years old subjects
- •genetically proven Gitelman syndrome
- •Normal EKG
- •Inform consent given
- •Affiliation to French Medicare assurance
- •Non inclusion Criteria for healthy subjects:
- •History of cardiac arrythmia or abnormal EKG
- •Recent or chronic diarrhea
- •Spontaneous low potassium intakes
- •Biological abnormality : SGOT or SGPT > 2.5 N, fasting hyperglycemia (> 6.5 mmol/l, anemia (hemoglobin< 12g/dL)
- •Single or functionally solitary kidney
- •Any severe allergies, or allergic history to any drug.
- •Predicted Difficulty monitoring and compliance.
- •Blood donation for less than 2 months.
- •Persons directly involved in the implementation of the Protocol.
- •Person in exclusion period in biomedical research.
- •Protected Person (person under guardianship, deprived of liberty, ...).
- •Taking medication in the previous 7 days (except paracetamol).
- •Chronic adrenal insufficiency.
- •Known allergy to any of the excipients of the RU 486 (colloidal anhydrous silica, maize starch, povidone, microcrystalline cellulose, magnesium stearate).
- •Severe asthma not controlled by treatment.
- •Porphyria hereditary.
- •Non inclusion Criteria for Gitelman patients:
- •People that did not give their consent or unable to understand the protocol.
- •Anemia (Hg <10 g / dL).
- •Clinically significant abnormality on the EKG.
- •Any severe allergies, or allergic history to any drug.
- •Treatment with corticosteroids.
- •Patient in exclusion period in biomedical research.
- •Protected Person (patient trust, deprived of liberty, ...)
排除标准
- 未提供
研究组 & 干预措施
RU 486 (mifepristone)
Subjects will receive 400 mg once a day of RU486
干预措施: Potassium depletion (Dietary Supplement)
Placebo
Subjects will receive placebo once a day
干预措施: Potassium depletion (Dietary Supplement)
结局指标
主要结局
Effect of potassium depletion on plasma progesterone (Change from Baseline of progesterone)
时间窗: Day 1 and Day 8 of placebo period of treatment (healthy subjects) or once (Gitelman patients)
Healthy subjects : Change from Baseline of progesterone in response to synacthen at day 8 in subject treated by placebo. Patients with Gitelman syndrome: Change from Baseline of progesterone in response to synacthen
次要结局
- Effect of potassium depletion on pulse pressure velocity (Pulse wave velocity and central blood pressure)(At Day 1 and Day 8 of each period of treatment)
- Effect of potassium depletion on plasma progesterone under RU486 (Change from Baseline of progesterone)(Day 1 and Day 8 of placebo period of treatment (healthy subjects) or once (Gitelman patients))
- effect of RU 486 on renal adaptation to potassium depletion (Plasma potassium and kaliuresis will be monitored )(Day 1 and day 8 of each period of treatment)