Clinical trial NCT01832532: A Pilot Study of the Effects on Sleep Disordered Breathing (SDB) When Using the Drug Liraglutide for 4 Weeks
Official title: Pilot 2: Glucagon-like Peptide-1 in Sleep Disordered Breathing
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Sleep Apnea
Sleep Disordered Breathing
Keywords: Sleep Apnea
Sleep Disordered Breathing
liraglutide
glucagon-like peptide-1 agonist
Orexin
leptin,
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: National Center for Research Resources (NCRR)
First posted: 2013-04-16
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open label, controlled study.

The investigators are studying if the FDA approved diabetes medicine liraglutide (Victoza®) can improve sleep apnea in adults. This study is testing liraglutide in 20 adults without diabetes that are diagnosed with sleep apnea.The treatment group will be compared to a control group of 10 adults without diabetes who have sleep apnea but will not use liraglutide. Both groups will continue receiving standard of care for their sleep apnea as prescribed by their managing sleep physician throughout their study participation.

Everyone in the study will have two study visits and one overnight sleep study for research. Subjects who have not had a recent sleep study but otherwise qualify for the study, will have an additional research sleep study to determine the baseline severity of their sleep apnea. The study visits include fasting blood samples and breathing tests (pulmonary function test and hypercapnic challenge). There will be weekly phone visits that include a questionnaire on sleepiness. The group that takes liraglutide will check their blood sugar two times a day while on the medicine.

Detailed description: This is a pilot study aimed at measuring the change in obstructive apnea/hypopnea index in non-diabetic patients being treated for the first time with the glucagon-like peptide-1 (GLP-1) agonist, Liraglutide. Sleep disordered breathing (SDB) consists of nocturnal alveolar hypoventilation and / or obstructive sleep apnea which result from abnormalities in upper airway tone and ventilation during sleep. The development of a new pharmacological treatment for sleep disordered breathing (SDB) could bring a breakthrough discovery that will impact a rapidly growing population of children and adults with this disorder. The investigators hypothesize that GLP-1 plays a central role in the improvement of SDB and that the administration of GLP-1 receptor agonist to patients with OSA will correct or improve SDB.

* Hypothesis 1: Administration of Liraglutide to patients with severe OSA defined as apnea hypopnea index ≥ 8 /hr. will result in a mean reduction in the index by a minimum of 50% after 4 weeks.
* Hypothesis 2: Administration of Liraglutide will result in significant increase in Orexin level, decrease in leptin, decrease in Epworth Sleepiness Scale (ESS) score and increase in carbon dioxide (CO2) chemosensitivity.

This is an open label, non-randomized, controlled pilot study. Subjects are heavy to obese non-diabetic adults that are diagnosed with sleep apnea. 20 subjects will be treated with liraglutide for 4 weeks and compared to 10 untreated controls.

Study time points are baseline and 4 weeks post treatment. Study procedures include pre and post treatment: fasting blood for glucose, hemoglobin A1C (HbA1C), Orexin and leptin; ESS questionnaire; pulmonary function test and hypercapnic challenge. The procedures also include a post treatment overnight research sleep study to measure change in apnea index from diagnostic sleep study done previous to study enrollment or if needed, the baseline research sleep study.

Eligibility criteria: Inclusion Criteria:

* Age 18-60 years
* Diagnosis of severe obstructive sleep apnea (OSA) AHI ≥ 8 /hour of sleep
* Ability and willingness to comply with all protocol procedures e.g. correct handling of trial product, compliance to visit schedule
* BMI of ≥ 27
* For Cohort 1: If female of childbearing capacity, willing to use acceptable birth control during use of study drug

Exclusion Criteria:

* A major medical condition such as renal or hepatic failure
* Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 inhibitors or insulin within the last 3 months prior to screening
* Diagnosis of type 1 or type 2 diabetes per judgment of the investigator
* BMI \< 27
* History of glycosylated hemoglobin (HbA1c) equal to or above 6.5%
* Significant craniofacial abnormalities that may cause OSA
* Respiratory and neuromuscular diseases that could interfere with the results of the trial in the opinion of the investigator
* Use of central stimulants, hypnotics, mirtazepine, opioids, trazodone or drugs in the incretin family within the previous 3 months prior to screening
* Previous surgical treatment for obesity
* Familial or personal history of Multiple Endocrine Neoplasia type 2 or familial Medullary Thyroid Carcinoma
* Personal or immediate family history of thyroid cancer
* History of chronic pancreatitis or idiopathic acute pancreatitis
* History of Major Depressive Disorder or suicide attempts
* Systolic blood pressure equal to or above 160 mmHg and/or diastolic blood pressure equal to or above 100 mmHg
* History of alcoholism
* Pregnancy or breastfeeding

Primary outcomes:
measure: Change in Apnea Hypopnea Index (AHI) From Baseline
timeFrame: Baseline and 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Raouf Amin, MD
role: PRINCIPAL_INVESTIGATOR
References: