Clinical Trial: Assessment of Desogestrel in Ondine Syndrome
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Assessment of Desogestrel for a Pharmacological Recovery of Ventilatory Activity in Congenital Central Hypoventilation Syndrome - Ondine Syndrome
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 Summary:
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
Sponsor: Assistance Publique - Hôpitaux de Paris
Current Primary Outcome: Increase in the ventilatory response to hypercapnia [ Time Frame: 112 days ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- 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 ]
Original Secondary Outcome: Same as current
Information By: Assistance Publique - Hôpitaux de Paris
Dates:
Date Received: November 17, 2010
Date Started: April 2011
Date Completion:
Last Updated: November 13, 2013
Last Verified: October 2012
