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

NCT02714400 | Completed Phase 4 Results

• 1 other identifier: UCSD141272ARM5-1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Obstructive Sleep Apnea

Keywords

Obstructive Sleep Apnea; Arousal threshold; Venlafaxine

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• Loop Gain

  Baseline and 7-day follow up

• Arousal Threshold

  Baseline and 7-day follow up

• Sleep Efficiency

  Baseline and 7-day follow up

Study Arms (2)

Venlafaxine

ACTIVE COMPARATOR

50mg of Venlafaxine before sleep

Drug: Venlafaxine

Placebo

PLACEBO COMPARATOR

One piece of placebo before sleep

Drug: Placebo

Interventions

Venlafaxine DRUG

Venlafaxine 50mg before sleep

Venlafaxine

Placebo DRUG

One piece of placebo before sleep

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18-70 years
• sleep study (with apnea hypopnea index\>5)
• Diagnosis of obstructive sleep apnea

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

University of California, San Diego

San Diego, California, 92093, United States

Location

Related Publications (6)

• 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.

  PMID: 23721582 BACKGROUND

• 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.

  PMID: 26715227 BACKGROUND

• 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.

  PMID: 26569377 BACKGROUND

• 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.

  PMID: 25321848 BACKGROUND

• 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.

  PMID: 23990246 BACKGROUND

• Schmickl CN, Li Y, Orr JE, Jen R, Sands SA, Edwards BA, DeYoung P, Owens RL, Malhotra A. Effect of Venlafaxine on Apnea-Hypopnea Index in Patients With Sleep Apnea: A Randomized, Double-Blind Crossover Study. Chest. 2020 Aug;158(2):765-775. doi: 10.1016/j.chest.2020.02.074. Epub 2020 Apr 9.

  PMID: 32278781 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Venlafaxine Hydrochloride

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Phenethylamines; Ethylamines; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Lipids

Results Point of Contact

• Title: Dillon Gilbertson
• Organization: UCSD

dcgilbertson@health.ucsd.edu

8582452155

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 26, 2016
• First Posted: March 21, 2016
• Study Start: March 1, 2016
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: April 17, 2020
• Results First Posted: April 17, 2020

Record last verified: 2020-04

Locations

US (1)