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

NCT01500473 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: CCI-11-00057
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Congenital Central Hypoventilation Syndrome

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (1)

Females with CCHS > 16 years old on desogestrel

EXPERIMENTAL

open label studied on drug.

Drug: Desogestrel

Interventions

Desogestrel DRUG

Reclipsen oral contraceptive pill with 0.03mg ethinyl estradiol and 0.15mg desogestrel

Also known as: Reclipsen

Females with CCHS > 16 years old on desogestrel

Eligibility Criteria

• Age: 16 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• diagnosed congenital central hypoventilation syndrome (CCHS)
• female
• greater than or equal to 16 years of age

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital Los Angeles: lead

Study Sites (1)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

MeSH Terms

Conditions

Congenital central hypoventilation syndrome

Interventions

Desogestrel

Intervention Hierarchy (Ancestors)

Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed. Only one subject was enrolled.

Results Point of Contact

• Title: Thomas Keens
• Organization: Children's Hospital Los Angeles

tkeens@chla.usc.edu

3233612101

Study Officials

• Iris Perez, MD

  Children's Hospital Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 22, 2011
• First Posted: December 28, 2011
• Study Start: February 1, 2012
• Primary Completion: May 11, 2016
• Study Completion: May 11, 2016
• Last Updated: November 18, 2023
• Results First Posted: September 28, 2023

Record last verified: 2023-10

Locations

US (1)