Assessment of Desogestrel in Ondine Syndrome (RESPIRONDINE)
Primary Purpose
Ondine Syndrome
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
desogestrel
Sponsored by
About this trial
This is an interventional treatment trial for Ondine Syndrome focused on measuring Desogestrel, Chemosensitivity
Eligibility Criteria
Inclusion criteria :
- Ondine syndrome
- Pubescent female
Exclusion criteria :
- Contra-indications to a treatment with desogestrel.
- Other treatment with estrogens or progestin that cannot be stopped.
Sites / Locations
- Pitie salpetriere hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
desogestrel
Arm Description
Tablets of 75 µg, once daily during 112 days
Outcomes
Primary Outcome Measures
Increase in the ventilatory response to hypercapnia
Secondary Outcome Measures
Ventilatory response to hypoxia
Activation of new cerebral regions in fMRI
Weaning from mechanical ventilation during sleep
Full Information
NCT ID
NCT01243697
First Posted
November 17, 2010
Last Updated
November 13, 2013
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT01243697
Brief Title
Assessment of Desogestrel in Ondine Syndrome
Acronym
RESPIRONDINE
Official Title
Assessment of Desogestrel for a Pharmacological Recovery of Ventilatory Activity in Congenital Central Hypoventilation Syndrome - Ondine Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The congenital central hypoventilation syndrome (CCHS), also known as the Ondine syndrome, is a very rare genetic disorder. In contrast with healthy people, patients do not increase breathing in response to an excess of carbon dioxide (CO2). As a consequence, they do not breath sufficiently, or even stop breathing, during sleep. Their survival depends only on mechanical respiratory assistance, all life long.
We have recently published two cases of recovery of a response to CO2 in patients taking desogestrel as a contraceptive pill. The goal of the study is therefore to assess the hypothesis that desogestrel will restore a respiratory response to CO2 in CCHS patients and allow them to breath sufficiently during sleep without mechanical assistance.
Detailed Description
Rationale of the study The congenital central hypoventilation syndrome (CCHS), also called Ondine syndrome or Ondine's curse, is a rare orphan disease associated with mutations of the PHOX 2B gene. It is characterized by an absence or a deep reduction in the ventilatory response to hypercapnia and hypoxia. As a consequence, life-threatening hypoventilation or apneas occur during sleep and, in some patients, also during wakefulness. Survival thus depends on mechanical ventilatory assistance (or on phrenic pacing), all life long. There is no pharmacological treatment.
We have fortuitously observed two cases of recovery of ventilatory response to hypercapnia in patients taking desogestrel, a very potent progestin, as a contraceptive treatment ("Straus, C., et al. Respir. Physiol. Neurobiol. 2010 ; 171 : 171-174").
The hypothesis of the research project stems from these observations. It assumes that desogestrel will restore a chemosensitivity to hypercapnia in Ondine patients that will allow them to breath sufficiently without mechanical ventilatory assistance during sleep.
The primary goal of the study will be to assess whether a treatment with desogestrel will restore a ventilatory response to hypercapnia. The secondary goal will be to evaluate whether this response will allow the patients to be weaned from mechanical ventilatory assistance during sleep.
Methods The study will take place in one unique hospital, the Pitie-Salpetriere Hospital in Paris, France. It will be conducted in volunteer pubescent female patients. Patients with contra-indications to desogestrel will not be included.
The ventilatory response to hypercapnia will be assessed through the rebreathing method and through a blinded procedure specifically designed for the study. Sleep and breathing during sleep will be assessed through polysomnography. Blood gas analysis as well as hormonal and ionic analysis of the blood will be performed. The ventilatory response to hypoxia will also be assessed. Changes in cerebral activation will be looked for using functional magnetic resonance imaging (fMRI).
Protocol Patients will be first assessed with all the tests mentioned in the above paragraph, except fMRI. Polysomnography will be performed under mechanical ventilation.
Patients who will not take any contraceptive oral treatment with estrogens or progestin and whose response to hypercapnia will be low enough will immediately continue the study. An fMRI will be performed and the patients will be prescribed desogestrel 75 µg daily.
Patients who will be under an oral contraceptive treatment with estrogens or progestin will have to stop it and to use mechanical contraception (condom). All the patients taking an oral contraceptive treatment will be assessed after having stopped these drugs, with all the tests mentioned in the "methods" paragraph, except fMRI. Polysomnography will be performed under mechanical ventilation. If their ventilatory response to hypercapnia will be low enough an fMRI will be performed and the patients will be prescribed desogestrel 75 µg daily.
All the patients will be assessed under treatment with desogestrel. If the slope of the ventilatory response to hypercapnia is more than 1L/min/mmHg, an attempt of weaning from mechanical ventilation during sleep will replace the usual polysomnography under mechanical ventilation. The patients will be admitted in an intensive care unit where they will sleep without ventilatory assistance. Polysomnographic recordings will be performed with a portable device. In case of prolonged hypopneas or apneas or in case of arterial desaturation, patients will be awakened and mechanical ventilation will be resumed. The attempt of weaning will be regarded as a failure. In the absence of those criteria, the weaning will be regarded as a possible success. However, the investigators will not prescribe to the patient to sleep without ventilatory assistance. Their attending physician will have to take the final decision regarding this issue.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ondine Syndrome
Keywords
Desogestrel, Chemosensitivity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
desogestrel
Arm Type
Experimental
Arm Description
Tablets of 75 µg, once daily during 112 days
Intervention Type
Drug
Intervention Name(s)
desogestrel
Intervention Description
Tablets of 75 µg, once daily during 112 days
Primary Outcome Measure Information:
Title
Increase in the ventilatory response to hypercapnia
Time Frame
112 days
Secondary Outcome Measure Information:
Title
Ventilatory response to hypoxia
Time Frame
112 days
Title
Activation of new cerebral regions in fMRI
Time Frame
112 days
Title
Weaning from mechanical ventilation during sleep
Time Frame
112 days
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria :
Ondine syndrome
Pubescent female
Exclusion criteria :
Contra-indications to a treatment with desogestrel.
Other treatment with estrogens or progestin that cannot be stopped.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
STRAUS Christian, MD, PhD
Organizational Affiliation
Pitie Salpetriere Hospital (APHP)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pitie salpetriere hospital
City
Paris
ZIP/Postal Code
75013
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
25268234
Citation
Sharman M, Gallea C, Lehongre K, Galanaud D, Nicolas N, Similowski T, Cohen L, Straus C, Naccache L. The cerebral cost of breathing: an FMRI case-study in congenital central hypoventilation syndrome. PLoS One. 2014 Sep 30;9(9):e107850. doi: 10.1371/journal.pone.0107850. eCollection 2014.
Results Reference
derived
PubMed Identifier
21801857
Citation
Straus C, Similowski T. Congenital central hypoventilation syndrome and desogestrel: a call for caution: addendum to "C. Straus, H. Trang, M.H. Becquemin, P. Touraine, T. Similowski, Chemosensitivity recovery in Ondine's curse syndrome under treatment with desogestrel" [Respir. Physiol. Neurobiol. 171 (2010) 171-174]. Respir Physiol Neurobiol. 2011 Sep 15;178(2):357-8. doi: 10.1016/j.resp.2011.07.007. Epub 2011 Jul 23.
Results Reference
derived
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Assessment of Desogestrel in Ondine Syndrome
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