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.

Study Overview

• Status: Terminated
• Conditions: Congenital Central Hypoventilation Syndrome
• Intervention / Treatment: Drug: Desogestrel

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Thomas Keens, MD; Phone Number: 323-361-2101
• Study Contact Backup: Name: Douglas LI, MD; Phone Number: 323-361-2101

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
      • Contact: Thomas Keens, MD; Phone Number: 323-361-2101

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 48 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Females with CCHS > 16 years old on desogestrel; open label studied on drug.	Drug: Desogestrel; Reclipsen oral contraceptive pill with 0.03mg ethinyl estradiol and 0.15mg desogestrel; Other Names: Reclipsen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoxic Ventilatory Response	Increase in minute ventilation as oxygen saturation of hemoglobin falls.	3 weeks
Hypercapnic Ventilatory Response	Increase in ventilation with increasing partial pressure of CO2	3 weeks
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.	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time That the Patient Maintains Adequate Ventilation	Time that the patient maintains oxygen saturation >80% and end tidal CO2 <65mm Hg	6 hours

Collaborators and Investigators

• Sponsor: Children's Hospital Los Angeles
• Investigators: Principal Investigator: Iris Perez, MD, Children's Hospital Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2012
• Primary Completion (Actual): May 11, 2016
• Study Completion (Actual): May 11, 2016

Study Registration Dates

• First Submitted: December 22, 2011
• First Submitted That Met QC Criteria: December 22, 2011
• First Posted (Estimated): December 28, 2011

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disease; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Respiratory Insufficiency; Syndrome; Hypoventilation; Sleep Apnea, Central; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Progestins; Desogestrel
• Other Study ID Numbers: CCI-11-00057

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No