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Trial record 3 of 4 for:    "Gitelman syndrome"

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

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ClinicalTrials.gov Identifier: NCT02297048
Recruitment Status : Completed
First Posted : November 21, 2014
Last Update Posted : October 1, 2015
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.

Condition or disease Intervention/treatment Phase
Gitelman Syndrome Potassium Depletion Dietary Supplement: Potassium depletion Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Monocentric STUDY, Randomised Double Blinded (Healthy Subjects, or Transversal (Patients With Gitelman Syndrome)
Study Start Date : July 2014
Actual Primary Completion Date : September 2015
Actual Study Completion Date : September 2015


Arm Intervention/treatment
Experimental: RU 486 (mifepristone)
Subjects will receive 400 mg once a day of RU486
Dietary Supplement: Potassium depletion
Healthy subjects will be submitted twice at 15-30 day interval, to a low potassium diet (20mmol/day)

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




Primary Outcome Measures :
  1. Effect of potassium depletion on plasma progesterone (Change from Baseline of progesterone) [ Time Frame: Day 1 and Day 8 of placebo period of treatment (healthy subjects) or once (Gitelman patients) ]

    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 :
  1. effect of RU 486 on renal adaptation to potassium depletion (Plasma potassium and kaliuresis will be monitored ) [ Time Frame: Day 1 and day 8 of each period of treatment ]
    Plasma potassium and kaliuresis will be monitored during the 7-days potassium depletion in subjects treated by RU486 or placebo, according randomization

  2. Effect of potassium depletion on pulse pressure velocity (Pulse wave velocity and central blood pressure) [ Time Frame: At Day 1 and Day 8 of each period of treatment ]
    Pulse wave velocity and central blood pressure are measured before and after 7 days of potassium deprivated diet.

  3. Effect of potassium depletion on plasma progesterone under RU486 (Change from Baseline of progesterone) [ Time Frame: Day 1 and Day 8 of placebo period of treatment (healthy subjects) or once (Gitelman patients) ]
    Healthy subjects : Change from Baseline of progesterone in response to synacthen at day 8 in subject treated by RU486.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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, ...)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02297048


Locations
France
European George Pompidou Hospital
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Anne Blanchard, MD, PhD Assistance Publique - Hôpitaux de Paris

Publications:
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02297048     History of Changes
Other Study ID Numbers: P120906
First Posted: November 21, 2014    Key Record Dates
Last Update Posted: October 1, 2015
Last Verified: September 2015

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Potassium intake
Progesterone
steroidogenesis
RU486
Synachtene test

Additional relevant MeSH terms:
Gitelman Syndrome
Syndrome
Hypokalemia
Potassium Deficiency
Disease
Pathologic Processes
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Water-Electrolyte Imbalance
Deficiency Diseases
Malnutrition
Nutrition Disorders