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

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

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.

Study Overview

• Status: Completed
• Conditions: Gitelman Syndrome
• Intervention / Treatment: Drug: TREATMENT

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hôpital Européen Georges Pompidou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amiloride, Indometacin, Eplerenone; Amiloride, indometacin(+Omeprazole), Eplerenone	Drug: TREATMENT; 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.; Other Names: MODAMINE; Inspra and CHRONOINDOCID
Experimental: Amiloride, Eplerenone, indometacin; Amiloride, Eplerenone, indometacin (+Omeprazole)	Drug: TREATMENT; 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.; Other Names: MODAMINE; Inspra and CHRONOINDOCID
Experimental: Eplerenone, Amiloride, indometacin; Eplerenone, Amiloride, indometacin (+Omeprazole)	Drug: TREATMENT; 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.; Other Names: MODAMINE; Inspra and CHRONOINDOCID
Experimental: Eplerenone, Indometacin, Amiloride	Drug: TREATMENT; 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.; Other Names: MODAMINE; Inspra and CHRONOINDOCID
Experimental: Indometacin, Eplerenone, Amiloride	Drug: TREATMENT; 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.; Other Names: MODAMINE; Inspra and CHRONOINDOCID
Experimental: Indometacin, Amiloride, Eplerenone	Drug: TREATMENT; 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.; Other Names: MODAMINE; Inspra and CHRONOINDOCID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Blanchard Anne, MD,PhD, APHP

Publications and helpful links

General Publications

• Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: June 16, 2010
• First Submitted That Met QC Criteria: June 16, 2010
• First Posted (Estimate): June 17, 2010

Study Record Updates

• Last Update Posted (Estimate): December 10, 2013
• Last Update Submitted That Met QC Criteria: December 9, 2013
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: Hypokalemia; Hypomagnesemia; Salt loosing nephropathy
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Genetic Diseases, Inborn; Renal Tubular Transport, Inborn Errors; Syndrome; Gitelman Syndrome
• Other Study ID Numbers: P071242