Therapeutic Effect of Desogestrel on Ventilatory Control in Patients With Congenital Central Hypoventilation Syndrome
Condition: Congenital Central Hypoventilation Syndrome
MeSH terms: Hypoventilation; Sleep Apnea, Central; Syndrome
Intervention: Desogestrel
Intervention description: Reclipsen oral contraceptive pill with 0.03mg ethinyl estradiol and 0.15mg desogestrel
Intervention MeSH terms: Desogestrel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: Female
Minimum age: 16 Years
Maximum age: 50 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  diagnosed congenital central hypoventilation syndrome (CCHS)

          -  female

          -  greater than or equal to 16 years of age

        Exclusion Criteria:

          -  less than 16 years of age

          -  male

          -  pregnant

          -  poor adherence to medications

          -  inability to perform pulmonary maneuvers for tests

          -  contraindications to oral contraceptives

          -  pulmonary hypertension