Assessment of Desogestrel in Ondine Syndrome (RESPIRONDINE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT01243697

Recruitment Status : Completed

First Posted : November 18, 2010

Last Update Posted : November 14, 2013

Sponsor:

Information provided by (Responsible Party):

Assistance Publique - Hôpitaux de Paris

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.

Condition or disease	Intervention/treatment	Phase
Ondine Syndrome	Drug: desogestrel	Phase 2 Phase 3

Show detailed description

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.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	6 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Assessment of Desogestrel for a Pharmacological Recovery of Ventilatory Activity in Congenital Central Hypoventilation Syndrome - Ondine Syndrome
Study Start Date :	April 2011
Actual Primary Completion Date :	September 2013
Actual Study Completion Date :	September 2013

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Congenital central hypoventilation syndrome

Drug Information available for: Desogestrel

Genetic and Rare Diseases Information Center resources: Congenital Central Hypoventilation Syndrome

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: desogestrel Tablets of 75 µg, once daily during 112 days	Drug: desogestrel Tablets of 75 µg, once daily during 112 days

Outcome Measures

Primary Outcome Measures :

Increase in the ventilatory response to hypercapnia [ Time Frame: 112 days ]

Secondary Outcome Measures :

Ventilatory response to hypoxia [ Time Frame: 112 days ]
Activation of new cerebral regions in fMRI [ Time Frame: 112 days ]
Weaning from mechanical ventilation during sleep [ Time Frame: 112 days ]

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	10 Years to 60 Years (Child, Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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): NCT01243697

Locations

Layout table for location information

France
Pitie salpetriere hospital
Paris, France, 75013

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Layout table for investigator information

Principal Investigator:	STRAUS Christian, MD, PhD	Pitie Salpetriere Hospital (APHP)

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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. Review.

Layout table for additonal information

Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT01243697
Other Study ID Numbers:	P101001
First Posted:	November 18, 2010 Key Record Dates
Last Update Posted:	November 14, 2013
Last Verified:	October 2012

Keywords provided by Assistance Publique - Hôpitaux de Paris:


Desogestrel Chemosensitivity

Additional relevant MeSH terms:

Layout table for MeSH terms

Sleep Apnea, Central Syndrome Disease Pathologic Processes Sleep Apnea Syndromes Apnea Respiration Disorders Respiratory Tract Diseases Sleep Disorders, Intrinsic Dyssomnias Sleep Wake Disorders	Nervous System Diseases Desogestrel Contraceptives, Oral, Synthetic Contraceptives, Oral Contraceptive Agents, Female Contraceptive Agents Reproductive Control Agents Physiological Effects of Drugs Progestins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists

To Top