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

Primary Purpose

Obstructive Sleep Apnea

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Venlafaxine
Placebo
Sponsored by
University of California, San Diego
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obstructive Sleep Apnea focused on measuring Obstructive Sleep Apnea, Arousal threshold, Venlafaxine

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California, San Diego

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Venlafaxine

Placebo

Arm Description

50mg of Venlafaxine before sleep

One piece of placebo before sleep

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
Arousal Threshold
Change from baseline in respiratory arousal threshold after single dose of Venlafaxine will be estimated.
Sleep Efficiency
Change from baseline in sleep efficiency after single dose of Venlafaxine will be estimated using overnight polysomnography.

Full Information

First Posted
February 26, 2016
Last Updated
April 7, 2020
Sponsor
University of California, San Diego
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1. Study Identification

Unique Protocol Identification Number
NCT02714400
Brief Title
The Impact of Venlafaxine on Apnea Hypopnea Index in Obstructive Sleep Apnea
Official Title
The Impact of Venlafaxine on Apnea Hypopnea Index in Patients With Obstructive Sleep Apnea
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
March 2016 (Actual)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstructive Sleep Apnea
Keywords
Obstructive Sleep Apnea, Arousal threshold, Venlafaxine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Venlafaxine
Arm Type
Active Comparator
Arm Description
50mg of Venlafaxine before sleep
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
One piece of placebo before sleep
Intervention Type
Drug
Intervention Name(s)
Venlafaxine
Intervention Description
Venlafaxine 50mg before sleep
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
One piece of placebo before sleep
Primary Outcome Measure Information:
Title
The Apnea Hypopnea Index
Description
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.
Time Frame
Baseline and 7-day follow up
Title
Nadir Oxygen Level During Sleep
Description
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.
Time Frame
Baseline and 7-day follow up
Secondary Outcome Measure Information:
Title
Loop Gain
Description
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.
Time Frame
Baseline and 7-day follow up
Title
Arousal Threshold
Description
Change from baseline in respiratory arousal threshold after single dose of Venlafaxine will be estimated.
Time Frame
Baseline and 7-day follow up
Title
Sleep Efficiency
Description
Change from baseline in sleep efficiency after single dose of Venlafaxine will be estimated using overnight polysomnography.
Time Frame
Baseline and 7-day follow up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University of California, San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23721582
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.
Results Reference
background
PubMed Identifier
26715227
Citation
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.
Results Reference
background
PubMed Identifier
26569377
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.
Results Reference
background
PubMed Identifier
25321848
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.
Results Reference
background
PubMed Identifier
23990246
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.
Results Reference
background
PubMed Identifier
32278781
Citation
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.
Results Reference
derived

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

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