Gitelman SyndromePhase 4DEPROGENCT02297048
Monocentric STUDY, Randomised Double Blinded (Healthy Subjects, or Transversal (Patients With Gitelman Syndrome)
A Phase 4 study testing Potassium depletion in people with Gitelman Syndrome and Potassium Depletion, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Gitelman Syndrome, Potassium Depletion
- What is being tested?
- Potassium depletion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteFrance
- Study dates
- Jul 2014to Sep 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
- 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, ...)
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Potassium depletion
- Keywords
- Potassium intake, Progesterone, steroidogenesis, RU486, Synachtene test
- Medical subject headings
- Gitelman Syndrome, Hypokalemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Potassium depletionDietary supplement
Healthy subjects will be submitted twice at 15-30 day interval, to a low potassium diet (20mmol/day)
| Study group | Role | What they receive |
|---|---|---|
| RU 486 (mifepristone) | Experimental | Subjects will receive 400 mg once a day of RU486 Receives: Dietary Supplement: Potassium depletion |
| Placebo | Placebo comparator | Subjects will receive placebo once a day Receives: Dietary Supplement: Potassium depletion |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Day 1 and Day 8 of placebo period of treatment (healthy subjects) or once (Gitelman patients)
Secondary outcomes (3)
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
Measured: Day 1 and day 8 of each period of treatment
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.
Measured: At Day 1 and Day 8 of each period of treatment
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.
Measured: Day 1 and Day 8 of placebo period of treatment (healthy subjects) or once (Gitelman patients)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2014 (estimated)
- Study startJul 2014
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Gitelman SyndromeStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne Blanchard, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02297048
- Sponsor's protocol ID
- P120906
- Acronym
- DEPROGE
- Status last verified
- Sep 2015
- First submitted
- 29 Oct 2014
- Last updated
- 1 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 21326170Blanchard 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.
PubMed 31369102
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monocentric STUDY, Randomised Double Blinded (Healthy Subjects, or Transversal (Patients With Gitelman Syndrome)
- ClinicalTrials.gov ID
- NCT02297048
- Acronym / sponsor ID
- DEPROGE / P120906
- Conditions
- Gitelman Syndrome, Potassium Depletion
- Keywords
- Potassium intake, Progesterone, steroidogenesis, RU486, Synachtene test
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jul 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 21 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RU 486 (mifepristone) | Experimental | Dietary Supplement: Potassium depletionSubjects will receive 400 mg once a day of RU486 |
| Placebo | Placebo comparator | Dietary Supplement: Potassium depletionSubjects will receive placebo once a day |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (41 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Potassium depletionHealthy subjects will be submitted twice at 15-30 day interval, to a low potassium diet (20mmol/day) | Dietary supplement | Placebo, RU 486 (mifepristone) |
Primary outcome
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
3 secondary outcomes
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
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
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2015.
- Background: PubMed 21326170Elabida 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.
- Derived from this study: PubMed 31369102Blanchard 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.
Related trials for Gitelman Syndrome
RecruitingObservational study
The Osteoarticular Manifestations in Patients With Gitelman Syndrome
Gitelman Syndrome, CPPD - Calcium Pyrophosphate Deposition Disease
RecruitingObservational study
National Registry of Rare Kidney Diseases
Adenine Phosphoribosyltransferase Deficiency, AH Amyloidosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne Blanchard, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Potassium depletion in people with Gitelman Syndrome and Potassium Depletion, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 41 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02297048, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2015.