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

Phase 2

Terminated

• Conditions: Congenital Central Hypoventilation Syndrome
• Interventions: Drug: Desogestrel

• Registration Number: NCT01500473
• Lead Sponsor: Children's Hospital Los Angeles

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-12-22
• Study First Submitted QC: 2011-12-22
• Study First Posted: 2011-12-28
• Study Start: 2012-02
• Primary Completion: 2016-05-11
• Study Completion: 2016-05-11
• Results First Submitted: 2023-08-31
• Results First Submitted QC: 2023-08-31
• Results First Posted: 2023-09-28
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-27
• Last Update Posted: 2023-11-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 1

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Females with CCHS > 16 years old on desogestrel	Desogestrel	open label studied on drug.

Primary Outcome Measures

Name	Time	Method
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.
Hypoxic Ventilatory Response	3 weeks	Increase in minute ventilation as oxygen saturation of hemoglobin falls.

Trial Locations

Locations (1)

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States