Monocentric STUDY, Randomised Double Blinded (Healthy Subjects, or Transversal (Patients With Gitelman Syndrome)

Gitelman Syndrome Clinical Trial

— DEPROGE  

Official title:

Monocentric STUDY, Randomised Double Blinded (Healthy Subjects, or Transversal (Patients With Gitelman Syndrome)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02297048
• Other study ID #: P120906
• Status: Completed
• Phase: Phase 4
• First received: October 29, 2014
• Last updated: September 30, 2015
• Start date: July 2014
• Est. completion date: September 2015

Study information

• Verified date: September 2015
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France:The French National agency for Medicines and Health Products Safety (ANSM)
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria 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, ...)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gitelman Syndrome
• Hypokalemia
• Potassium Depletion
• Syndrome

Intervention

Dietary Supplement:
• Potassium depletion
Healthy subjects will be submitted twice at 15-30 day interval, to a low potassium diet (20mmol/day)

Locations

Country	Name	City	State
France	European George Pompidou Hospital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (1)

Elabida B, Edwards A, Salhi A, Azroyan A, Fodstad H, Meneton P, Doucet A, Bloch-Faure M, Crambert G. Chronic potassium depletion increases adrenal progesterone production that is necessary for efficient renal retention of potassium. Kidney Int. 2011 Aug;80(3):256-62. doi: 10.1038/ki.2011.15. Epub 2011 Feb 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of potassium depletion on plasma progesterone (Change from Baseline of progesterone)	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	Day 1 and Day 8 of placebo period of treatment (healthy subjects) or once (Gitelman patients)	No
Secondary	effect of RU 486 on renal adaptation to potassium depletion (Plasma potassium and kaliuresis will be monitored )	Plasma potassium and kaliuresis will be monitored during the 7-days potassium depletion in subjects treated by RU486 or placebo, according randomization	Day 1 and day 8 of each period of treatment	Yes
Secondary	Effect of potassium depletion on pulse pressure velocity (Pulse wave velocity and central blood pressure)	Pulse wave velocity and central blood pressure are measured before and after 7 days of potassium deprivated diet.	At Day 1 and Day 8 of each period of treatment	No
Secondary	Effect of potassium depletion on plasma progesterone under RU486 (Change from Baseline of progesterone)	Healthy subjects : Change from Baseline of progesterone in response to synacthen at day 8 in subject treated by RU486.	Day 1 and Day 8 of placebo period of treatment (healthy subjects) or once (Gitelman patients)	No