Congenital Central Hypoventilation Syndrome
Conditions
Brief 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.
Interventions
DRUGDesogestrel
Reclipsen oral contraceptive pill with 0.03mg ethinyl estradiol and 0.15mg desogestrel
Sponsors
Children's Hospital Los Angeles
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hypoxic Ventilatory Response | 3 weeks | Increase in minute ventilation as oxygen saturation of hemoglobin falls. |
| Hypercapnic Ventilatory Response | 3 weeks | Increase in ventilation with increasing partial pressure of CO2 |
| Time Maintained Ventilation Off Mechanical Ventilation During Sleep. | 3 weeks | length of time the subject could breathe adequately spontaneously until SpO2 fell below 80% and or PetCO2 rose above 65 mmHg. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Females With CCHS > 16 Years Old on Desogetrel open label studied on drug.
Desogestrel: Reclipsen oral contraceptive pill with 0.03mg ethinyl estradiol and 0.15mg desogestrel | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Females With CCHS > 16 Years Old on Desogetrel |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Hypercapnic Ventilatory Response
Increase in ventilation with increasing partial pressure of CO2
Time frame: 3 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Females With CCHS > 16 Years Old on Desogetrel | Hypercapnic Ventilatory Response | -0.520 liters per minute/ mmHg PCO2 |
Primary
Hypoxic Ventilatory Response
Increase in minute ventilation as oxygen saturation of hemoglobin falls.
Time frame: 3 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Females With CCHS > 16 Years Old on Desogetrel | Hypoxic Ventilatory Response | 0 subjects with positive response |
Primary
Time Maintained Ventilation Off Mechanical Ventilation During Sleep.
length of time the subject could breathe adequately spontaneously until SpO2 fell below 80% and or PetCO2 rose above 65 mmHg.
Time frame: 3 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Females With CCHS > 16 Years Old on Desogetrel | Time Maintained Ventilation Off Mechanical Ventilation During Sleep. | 89 seconds |