The Impact of Venlafaxine on Apnea Hypopnea Index in Obstructive Sleep Apnea

Obstructive Sleep Apnea Clinical Trial

Official title:

The Impact of Venlafaxine on Apnea Hypopnea Index in Patients With Obstructive Sleep Apnea

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02714400
• Other study ID #: UCSD141272ARM5-1
• Status: Completed
• Phase: Phase 4
• Start date: March 2016
• Est. completion date: July 2016

Study information

• Verified date: April 2020
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators hypothesis is that obstructive sleep apnea (OSA) patients with a low arousal threshold may wake up too early during a respiratory event, before upper airway muscles can be activated to achieve stable ventilation. Thus, strategies to manipulate the respiratory arousal threshold could potentially improve the quality of sleep and sleep disordered breathing. Agents that raise arousal threshold are therefore likely to benefit some patients with OSA. The overall goal of this project is to determine the importance of the arousal threshold in OSA, determine which patients might benefit from a raised arousal threshold, and test this hypothesis by using pharmacological manipulation of the arousal threshold to achieve this goal.

Description:

This study is a randomized double-blinded crossover pilot study. The investigators will test whether Venlafaxine has important effects on the apnea hypopnea index. Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) for the treatment of depression and anxiety. Venlafaxine increases serum serotonin level, which may affect arousal threshold. Furthermore, higher serotonin level theoretically may improve muscle tone, including upper airway muscle. Therefore, the investigators hypothesize that venlafaxine may decrease arousal threshold and improve muscle tone, leading to improvement of OSA.

Eligible participants will undergo overnight polysomonography as described below and will receive either Venlafaxine(50 mg 2 hour prior to sleep) or placebo (in random order) followed roughly 7 days later with placebo or donepezil. This aim will allow us to test the impact of Venlafaxine on the apnea hypopnea index.

The change in apnea hypopnea index will be compared in the Venlafaxine groups with the placebo group.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Ages 18-70 years

• sleep study (with apnea hypopnea index>5)

• Diagnosis of obstructive sleep apnea

Exclusion Criteria:

• Any known cardiac (apart from treated hypertension), pulmonary (including uncontrolled asthma), renal, neurologic (including epilepsy), neuromuscular, or hepatic disease.

• Susceptible to stomach ulcers.

• co-administration of MAO inhibitors intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing the MAO inhibitor); initiation of MAO inhibitor intended to treat psychiatric disorders within 7 days of discontinuing venlafaxine; initiation in patients receiving linezolid or intravenous methylene blue

• Pregnant women.

• History of hypersensitivity to Afrin, Lidocaine (all Aims) or venlafaxine

• History of bleeding diathesis and/or gastrointestinal bleeding.

• Glaucoma and Urinary Retention

• Use of any medications that may affect sleep or breathing.

• Use of any medications that have known interaction with venlafaxine and the interaction may significantly increase the risk of the subject or decrease the therapeutic effect of the medication.

• A psychiatric disorder, other than mild depression; e.g. schizophrenia, bipolar disorder, major depression, panic or anxiety disorders.

• Substantial cigarette (>5/day), alcohol (>3oz/day) or use of illicit drugs.

• More than 10 cups of beverages with caffeine (coffee, tea, soda/pop) per day.

• Desaturations to below 70% lasting greater than 10 seconds in duration per event

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Venlafaxine
Venlafaxine 50mg before sleep
• Placebo
One piece of placebo before sleep

Locations

Country	Name	City	State
United States	University of California, San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

References & Publications (5)

Carter SG, Berger MS, Carberry JC, Bilston LE, Butler JE, Tong BK, Martins RT, Fisher LP, McKenzie DK, Grunstein RR, Eckert DJ. Zopiclone Increases the Arousal Threshold without Impairing Genioglossus Activity in Obstructive Sleep Apnea. Sleep. 2016 Apr 1;39(4):757-66. doi: 10.5665/sleep.5622. — View Citation

Deacon NL, Jen R, Li Y, Malhotra A. Treatment of Obstructive Sleep Apnea. Prospects for Personalized Combined Modality Therapy. Ann Am Thorac Soc. 2016 Jan;13(1):101-8. doi: 10.1513/AnnalsATS.201508-537FR. Review. — View Citation

Eckert DJ, White DP, Jordan AS, Malhotra A, Wellman A. Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Respir Crit Care Med. 2013 Oct 15;188(8):996-1004. doi: 10.1164/rccm.201303-0448OC. — View Citation

Eckert DJ, Younes MK. Arousal from sleep: implications for obstructive sleep apnea pathogenesis and treatment. J Appl Physiol (1985). 2014 Feb 1;116(3):302-13. doi: 10.1152/japplphysiol.00649.2013. Epub 2013 Aug 29. Review. — View Citation

Edwards BA, Eckert DJ, McSharry DG, Sands SA, Desai A, Kehlmann G, Bakker JP, Genta PR, Owens RL, White DP, Wellman A, Malhotra A. Clinical predictors of the respiratory arousal threshold in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2014 Dec 1;190(11):1293-300. doi: 10.1164/rccm.201404-0718OC. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Apnea Hypopnea Index	The Apnea hypopnea index is an index used to indicate the severity of sleep apnea. It is represented by the number of apnea and hypopnea events per hour of sleep. The change from baseline in apnea hypopnea index after a single dose of Venlafaxine will be evaluated using overnight polysomnography. An apnea hypopnea index less than five events per hour is considered within normal limits.	Baseline and 7-day follow up
Primary	Nadir Oxygen Level During Sleep	Change from baseline in nadir oxygen level during sleep after a single dose of Venlafaxine will be evaluated using overnight polysomnography. A lower blood oxygen saturation during sleep is associated with a more severe obstructive sleep apnea.	Baseline and 7-day follow up
Secondary	Loop Gain	Loop gain 1 is used to describe the stability of ventilatory control. The change from baseline in loop gain after a single dose of Venlafaxine will be estimated.	Baseline and 7-day follow up
Secondary	Arousal Threshold	Change from baseline in respiratory arousal threshold after single dose of Venlafaxine will be estimated.	Baseline and 7-day follow up
Secondary	Sleep Efficiency	Change from baseline in sleep efficiency after single dose of Venlafaxine will be estimated using overnight polysomnography.	Baseline and 7-day follow up