Input of the Use of Indometacin in Gitelman Syndrome as Compared to Potassium Sparing Diuretics

Study Overview
=================
Brief Summary
-----------------
Gitelman syndrome is a rare renal disease where the kidneys are unable to normally retain some salts (sodium, potassium and magnesium). Main consequences of these renal leaks of salts are a tendency toward low blood pressure, hypokalemia and hypomagnesemia both contributing to cardiac and muscles symptoms.

Detailed Description
-----------------
Patients with received in random order 75mg/day indometacin (Chronoindocid®), 10-20 mg/day amiloride and 50-150 mg /day eplerenone (Inspra ®). The three 6 weeks-periods of treatment will be followed by six weeks washout period. 3-6 weeks before the first period of treatment, a supplementation with potassium and magnesium will be orally given, and maintained at the same dose throughout the study and stoped 6 weeks after the end of the third period of treatment.

Official Title
-----------------
Evaluation of Safety and Efficacity of Indometacin and Two Potassium Sparing Diuretics in Adult Patients Affected by Gitelman Syndrome

Conditions
-----------------
Gitelman Syndrome

Intervention / Treatment
-----------------
* Drug: TREATMENT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients 18-60 yrs old, both sex, with genetically proven Gitelman's syndrome, under birth pill control for woman. Exclusion Criteria: counter-indication to treatment under study Other diuretic or NAIS treatments than amiloride, spironolactone, or indometacin

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amiloride, Indometacin, Eplerenone<br>Amiloride, indometacin(+Omeprazole), Eplerenone | Drug: TREATMENT<br>* Patients with received in random order 75mg/day indometacin(chronoindocid®), 10-20 mg/day amiloride and 50-150 mg /day eplerenone (Inspra ®). The three 6 weeks-periods of treatment will be followed by six weeks washout period. 3-6 weeks before the first period of treatment, a supplementation with potassium and magnesium will be orally given, and maintained at the same dose throughout the study and stoped 6 weeks after the end of the third period of treatment.<br>* Other names: MODAMINE; Inspra and CHRONOINDOCID;|
| Experimental: Amiloride, Eplerenone, indometacin<br>Amiloride, Eplerenone, indometacin (+Omeprazole) | Drug: TREATMENT<br>* Patients with received in random order 75mg/day indometacin(chronoindocid®), 10-20 mg/day amiloride and 50-150 mg /day eplerenone (Inspra ®). The three 6 weeks-periods of treatment will be followed by six weeks washout period. 3-6 weeks before the first period of treatment, a supplementation with potassium and magnesium will be orally given, and maintained at the same dose throughout the study and stoped 6 weeks after the end of the third period of treatment.<br>* Other names: MODAMINE; Inspra and CHRONOINDOCID;|
| Experimental: Eplerenone, Amiloride, indometacin<br>Eplerenone, Amiloride, indometacin (+Omeprazole) | Drug: TREATMENT<br>* Patients with received in random order 75mg/day indometacin(chronoindocid®), 10-20 mg/day amiloride and 50-150 mg /day eplerenone (Inspra ®). The three 6 weeks-periods of treatment will be followed by six weeks washout period. 3-6 weeks before the first period of treatment, a supplementation with potassium and magnesium will be orally given, and maintained at the same dose throughout the study and stoped 6 weeks after the end of the third period of treatment.<br>* Other names: MODAMINE; Inspra and CHRONOINDOCID;|
| Experimental: Eplerenone, Indometacin, Amiloride<br>Eplerenone, Indometacin, Amiloride | Drug: TREATMENT<br>* Patients with received in random order 75mg/day indometacin(chronoindocid®), 10-20 mg/day amiloride and 50-150 mg /day eplerenone (Inspra ®). The three 6 weeks-periods of treatment will be followed by six weeks washout period. 3-6 weeks before the first period of treatment, a supplementation with potassium and magnesium will be orally given, and maintained at the same dose throughout the study and stoped 6 weeks after the end of the third period of treatment.<br>* Other names: MODAMINE; Inspra and CHRONOINDOCID;|
| Experimental: Indometacin, Eplerenone, Amiloride<br>Indometacin, Eplerenone, Amiloride | Drug: TREATMENT<br>* Patients with received in random order 75mg/day indometacin(chronoindocid®), 10-20 mg/day amiloride and 50-150 mg /day eplerenone (Inspra ®). The three 6 weeks-periods of treatment will be followed by six weeks washout period. 3-6 weeks before the first period of treatment, a supplementation with potassium and magnesium will be orally given, and maintained at the same dose throughout the study and stoped 6 weeks after the end of the third period of treatment.<br>* Other names: MODAMINE; Inspra and CHRONOINDOCID;|
| Experimental: Indometacin, Amiloride, Eplerenone<br>Indometacin, Amiloride, Eplerenone | Drug: TREATMENT<br>* Patients with received in random order 75mg/day indometacin(chronoindocid®), 10-20 mg/day amiloride and 50-150 mg /day eplerenone (Inspra ®). The three 6 weeks-periods of treatment will be followed by six weeks washout period. 3-6 weeks before the first period of treatment, a supplementation with potassium and magnesium will be orally given, and maintained at the same dose throughout the study and stoped 6 weeks after the end of the third period of treatment.<br>* Other names: MODAMINE; Inspra and CHRONOINDOCID;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy of indomethacin on hypokalemia versus potassium and magnesium supplementation alone |  | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effectiveness of indomethacin on disorders possibly induced by chronic hypokalemia and /or hypomagnesemia (EKG, lipid disorders related to insulin resistance, glucose/ insulin ratio) |  | 2 months | 
| To evaluate the effectiveness of eplerenone and amiloride on hypokalemia. |  | 2 months | 
| To evaluate and compare indomethacin, eplerenone or amiloride in terms of efficiency on biological and hormonal disorders | To evaluate and compare indomethacin, eplerenone or amiloride in terms of efficiency on biological and hormonal disorders other than hypokalemia (hypomagnesemia, hyperaldosteronism), glomerular filtration rate, hypotension, clinical tolerance, and quality of life. | 2 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hypokalemia, Hypomagnesemia, Salt loosing nephropathy