Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01243697 |
| Other study ID # |
P101001 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2/Phase 3
|
| First received |
November 17, 2010 |
| Last updated |
November 13, 2013 |
| Start date |
April 2011 |
| Est. completion date |
September 2013 |
Study information
| Verified date |
October 2012 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
France: Ministry of Health |
| Study type |
Interventional
|
Clinical Trial 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.
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.
