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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02714400

Enrollment

Registered

2016-03-21

Start date

2016-03-31

Completion date

2016-07-31

Last updated

2020-04-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obstructive Sleep Apnea

Keywords

Obstructive Sleep Apnea, Arousal threshold, Venlafaxine

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.

Interventions

DRUGVenlafaxine

Venlafaxine 50mg before sleep

DRUGPlacebo

One piece of placebo before sleep

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

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

Design outcomes

Primary

Measure	Time frame	Description
The Apnea Hypopnea Index	Baseline and 7-day follow up	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	Baseline and 7-day follow up	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

Measure	Time frame	Description
Loop Gain	Baseline and 7-day follow up	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	Baseline and 7-day follow up	Change from baseline in respiratory arousal threshold after single dose of Venlafaxine will be estimated.
Sleep Efficiency	Baseline and 7-day follow up	Change from baseline in sleep efficiency after single dose of Venlafaxine will be estimated using overnight polysomnography.

Countries

United States

Participant flow

Participants by arm

Arm	Count
All Analyzed Participants All participants who were randomized, completed both study nights, and were included in the analysis.	20
Total	20

Baseline characteristics

Characteristic	All Analyzed Participants
Age, Continuous	53.8 Years STANDARD_DEVIATION 8.1
Region of Enrollment United States	20 participants
Sex: Female, Male Female	6 Participants
Sex: Female, Male Male	14 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 20	0 / 20
other Total, other adverse events	2 / 20	1 / 20
serious Total, serious adverse events	0 / 20	0 / 20

Outcome results

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.