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

NCT ID: NCT02297048

Last Updated: 2015-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2015-09-30

Brief 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.

Detailed 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.

Conditions

Gitelman Syndrome; Potassium Depletion

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

RU 486 (mifepristone)

Subjects will receive 400 mg once a day of RU486

Group Type: EXPERIMENTAL

Potassium depletion

Intervention Type: DIETARY_SUPPLEMENT

Healthy subjects will be submitted twice at 15-30 day interval, to a low potassium diet (20mmol/day)

Placebo

Subjects will receive placebo once a day

Group Type: PLACEBO_COMPARATOR

Potassium depletion

Intervention Type: DIETARY_SUPPLEMENT

Healthy subjects will be submitted twice at 15-30 day interval, to a low potassium diet (20mmol/day)

Interventions

Potassium depletion

Healthy subjects will be submitted twice at 15-30 day interval, to a low potassium diet (20mmol/day)

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• 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

• 18-75 Years old subjects
• genetically proven Gitelman syndrome
• Normal EKG
• Inform consent given
• Affiliation to French Medicare assurance

• 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.

• 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, ...)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anne Blanchard, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

European George Pompidou Hospital

Paris, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 21326170 (View on PubMed)

Blanchard A, Brailly Tabard S, Lamaziere A, Bergerot D, Zhygalina V, Lorthioir A, Jacques A, Hourton D, Azizi M, Crambert G. Adrenal adaptation in potassium-depleted men: role of progesterone? Nephrol Dial Transplant. 2020 Nov 1;35(11):1901-1908. doi: 10.1093/ndt/gfz135.

Reference Type: DERIVED

PMID: 31369102 (View on PubMed)

Other Identifiers

P120906

Identifier Type: -

Identifier Source: org_study_id