Therapeutic Effect of Desogestrel on Ventilatory Control in Patients With Congenital Central Hypoventilation Syndrome

Background: Congenital Central Hypoventilation Syndrome (CCHS) is a rare disorder of
automatic control of breathing. This disease can manifest as early as birth. Patients with
this disease have a fundamental lack of central drive breathing. They do not mount any
responses to hypoxia or hypercapnia during sleep or wakefulness. This places them at risk of
injury or death whenever they are not consciously breathing. They require lifelong assisted
ventilation while sleeping, and some while awake. Progesterone is a known respiratory
stimulant in normal individuals, and it has been shown in one study of 2 patients that this
drug may improve CO2 responsiveness in patients with CCHS. However, this observation
requires confirmation.

Hypothesis: Exogenous progesterone (in oral contraception pills) will improve CO2
responsivity by hyperoxic hypercapnic ventilatory response testing, hypoxic responsivity
using 5-breath nitrogen breathing, hyperoxic ventilatory response while breathing 100%
oxygen, and improve spontaneous ventilation during sleep in CCHS females >15-years of age.
The progesterone will also depress ventilatory response using a hyperoxia test.

Study Methodology: Baseline measures of CO2 and oxygen responsivity, and spontaneous
ventilation during sleep, will be performed at baseline and after 3-weeks of taking a
progesterone containing oral contraceptive agent. CO2 responsivity will be measured using a
hyperoxic hypercapnic ventilatory response test. Hypoxic responsivity will be measured using
a 5-breath 100% nitrogen breathing test. Hyperoxic responsivity will be measured by having
subjects breathe 100% oxygen for 2-minutes. Subjects will perform an overnight polysomnogram
to assess adequacy of gas exchange during spontaneous breathing while asleep. A progesterone
containing oral contraception pill will then be given for 3-weeks, and the above measures
repeated. Serum progesterone will be measured at baseline and at the time of study.