A Pilot Study of the Effects on Sleep Disordered Breathing (SDB) When Using the Drug Liraglutide for 4 Weeks

• Sponsor: Children's Hospital Medical Center, Cincinnati (Other)
• Overall Status: Completed
• CT.gov ID: NCT01832532
• Collaborator: National Center for Research Resources (NCRR) (NIH)
• Enrollment: 34
• Location: 1
• Arms: 2
• Duration (Months): 32
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sleep Apnea; Sleep Disordered Breathing	Drug: liraglutide	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot 2: Glucagon-like Peptide-1 in Sleep Disordered Breathing
• Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment group- liraglutide Treatment group- liraglutide daily use of drug. Titrated up from 0.6mg/day to 1.8mg/day or highest tolerated dose.	Drug: liraglutide; daily use of drug. Titrated up from 0.6mg/day to 1.8mg/day or highest tolerated dose; Other Names: Other name- Victoza
No Intervention: Control group Control group

Outcome Measures

Primary Outcome Measures

1. Change in Apnea Hypopnea Index (AHI) From Baseline [Baseline and 4 weeks]

   Change in the number of apneas plus hypopnea events per hour of sleep from baseline at end of study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

• Children's Hospital Medical Center, Cincinnati
• National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Raouf Amin, MD, Children's Hospital Medical Center, Cincinnati

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT01832532
• Other Study ID Numbers: CIN001Pilot 2GLP; UL1RR026314
• First Posted: Apr 16, 2013
• Last Update Posted: Oct 20, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Children's Hospital Medical Center, Cincinnati: Sleep Apnea; Sleep Disordered Breathing; liraglutide; glucagon-like peptide-1 agonist; Orexin; leptin,
• Additional relevant MeSH terms: Sleep Apnea Syndromes; Respiratory Aspiration; Liraglutide

Study Results

Participant Flow

Pre-assignment Detail	Enrollment fell short of goal for each cohort

Arm/Group Title	Treatment Group- Liraglutide	Control Group
Arm/Group Description	Treatment group- liraglutide daily use of drug. Titrated up from 0.6mg/day to 1.8mg/day or highest tolerated dose. liraglutide: daily use of drug. Titrated up from 0.6mg/day to 1.8mg/day or highest tolerated dose	Control group
Period Title: Overall Study
STARTED	23	11
COMPLETED	18	9
NOT COMPLETED	5	2

Baseline Characteristics

Arm/Group Title	Treatment Group- Liraglutide	Control Group	Total
Arm/Group Description	Treatment group- liraglutide daily use of drug. Titrated up from 0.6mg/day to 1.8mg/day or highest tolerated dose. liraglutide: daily use of drug. Titrated up from 0.6mg/day to 1.8mg/day or highest tolerated dose	Control group	Total of all reporting groups
Overall Participants	18	9	27
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	18 100%	9 100%	27 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47 (8)	44.5 (10.6)	46.2 (9)
Sex: Female, Male (Count of Participants)
Female	5 27.8%	2 22.2%	7 25.9%
Male	13 72.2%	7 77.8%	20 74.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 11.1%	2 22.2%	4 14.8%
White	16 88.9%	7 77.8%	23 85.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	18 100%	9 100%	27 100%

Outcome Measures

1. Primary Outcome

Title	Change in Apnea Hypopnea Index (AHI) From Baseline
Description	Change in the number of apneas plus hypopnea events per hour of sleep from baseline at end of study.
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Group- Liraglutide	Control Group
Arm/Group Description	Treatment group- liraglutide daily use of drug. Titrated up from 0.6mg/day to 1.8mg/day or highest tolerated dose. liraglutide: daily use of drug. Titrated up from 0.6mg/day to 1.8mg/day or highest tolerated dose	Control group
Measure Participants	18	9
Mean (Standard Deviation) [apnea / hypopnea events per hour sleep]	38.2 (30)	34 (20)

Adverse Events

Time Frame	8 weeks
Arm/Group Title	Treatment Group- Liraglutide		Control Group
Arm/Group Description	Treatment group- liraglutide daily use of drug. Titrated up from 0.6mg/day to 1.8mg/day or highest tolerated dose. liraglutide: daily use of drug. Titrated up from 0.6mg/day to 1.8mg/day or highest tolerated dose		Control group
All Cause Mortality
	Treatment Group- Liraglutide		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/9 (0%)
Serious Adverse Events
	Treatment Group- Liraglutide		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Treatment Group- Liraglutide		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.