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

Primary Purpose

Gitelman Syndrome, Potassium Depletion

Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Potassium depletion
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gitelman Syndrome focused on measuring Potassium intake, Progesterone, steroidogenesis, RU486, Synachtene test

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)MaleAccepts Healthy Volunteers

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, ...)

Sites / Locations

  • European George Pompidou Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

RU 486 (mifepristone)

Placebo

Arm Description

Subjects will receive 400 mg once a day of RU486

Subjects will receive placebo once a day

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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.
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.

Full Information

First Posted
October 29, 2014
Last Updated
September 30, 2015
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT02297048
Brief Title
Monocentric STUDY, Randomised Double Blinded (Healthy Subjects, or Transversal (Patients With Gitelman Syndrome)
Acronym
DEPROGE
Official Title
Monocentric STUDY, Randomised Double Blinded (Healthy Subjects, or Transversal (Patients With Gitelman Syndrome)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
July 2014 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gitelman Syndrome, Potassium Depletion
Keywords
Potassium intake, Progesterone, steroidogenesis, RU486, Synachtene test

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RU 486 (mifepristone)
Arm Type
Experimental
Arm Description
Subjects will receive 400 mg once a day of RU486
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will receive placebo once a day
Intervention Type
Dietary Supplement
Intervention Name(s)
Potassium depletion
Intervention Description
Healthy subjects will be submitted twice at 15-30 day interval, to a low potassium diet (20mmol/day)
Primary Outcome Measure Information:
Title
Effect of potassium depletion on plasma progesterone (Change from Baseline of progesterone)
Description
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
Time Frame
Day 1 and Day 8 of placebo period of treatment (healthy subjects) or once (Gitelman patients)
Secondary Outcome Measure Information:
Title
effect of RU 486 on renal adaptation to potassium depletion (Plasma potassium and kaliuresis will be monitored )
Description
Plasma potassium and kaliuresis will be monitored during the 7-days potassium depletion in subjects treated by RU486 or placebo, according randomization
Time Frame
Day 1 and day 8 of each period of treatment
Title
Effect of potassium depletion on pulse pressure velocity (Pulse wave velocity and central blood pressure)
Description
Pulse wave velocity and central blood pressure are measured before and after 7 days of potassium deprivated diet.
Time Frame
At Day 1 and Day 8 of each period of treatment
Title
Effect of potassium depletion on plasma progesterone under RU486 (Change from Baseline of progesterone)
Description
Healthy subjects : Change from Baseline of progesterone in response to synacthen at day 8 in subject treated by RU486.
Time Frame
Day 1 and Day 8 of placebo period of treatment (healthy subjects) or once (Gitelman patients)

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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, ...)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne Blanchard, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
European George Pompidou Hospital
City
Paris
ZIP/Postal Code
75015
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
21326170
Citation
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.
Results Reference
background
PubMed Identifier
31369102
Citation
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.
Results Reference
derived

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

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