Obstructive Sleep ApneaPhase 4NCT02714400
The Impact of Venlafaxine on Apnea Hypopnea Index in Obstructive Sleep Apnea
A Phase 4 study testing Venlafaxine in people with Obstructive Sleep Apnea, run by University of California, San Diego at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Obstructive Sleep Apnea
- What is being tested?
- Venlafaxine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2016to Jul 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages 18-70 years
- sleep study (with apnea hypopnea index>5)
- Diagnosis of obstructive sleep apnea
Who cannot join
- 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.
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
San Diego, California, 92093
About this study
Official title: The Impact of Venlafaxine on Apnea Hypopnea Index in Patients With Obstructive Sleep Apnea
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.
Read the 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.
- Conditions
- Obstructive Sleep Apnea
- Being tested
- Venlafaxine, Placebo
- Keywords
- Obstructive Sleep Apnea, Arousal threshold, Venlafaxine
- Medical subject headings
- Sleep Apnea, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenlafaxineDrug
Venlafaxine 50mg before sleep
PlaceboDrug
One piece of placebo before sleep
| Study group | Role | What they receive |
|---|---|---|
| Venlafaxine | Active comparator | 50mg of Venlafaxine before sleep Receives: Drug: Venlafaxine |
| Placebo | Placebo comparator | One piece of placebo before sleep Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline and 7-day follow up
Secondary outcomes (3)
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.
Measured: Baseline and 7-day follow up
Arousal Threshold
Change from baseline in respiratory arousal threshold after single dose of Venlafaxine will be estimated.
Measured: Baseline and 7-day follow up
Sleep Efficiency
Change from baseline in sleep efficiency after single dose of Venlafaxine will be estimated using overnight polysomnography.
Measured: Baseline and 7-day follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2016 (estimated)
- Study startMar 2016
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Obstructive Sleep ApneaStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert L. Owens, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02714400
- Sponsor's protocol ID
- UCSD141272ARM5-1
- Status last verified
- Apr 2020
- First submitted
- 26 Feb 2016
- Last updated
- 17 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 23721582Carter 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.
PubMed 26715227Deacon 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.
PubMed 26569377Edwards 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.
PubMed 25321848Eckert 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.
PubMed 23990246Schmickl 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.
PubMed 32278781
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Venlafaxine on Apnea Hypopnea Index in Patients With Obstructive Sleep Apnea
- ClinicalTrials.gov ID
- NCT02714400
- Acronym / sponsor ID
- UCSD141272ARM5-1
- Conditions
- Obstructive Sleep Apnea
- Keywords
- Obstructive Sleep Apnea, Arousal threshold, Venlafaxine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- Mar 2016 (actual)
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 21 Mar 2016 (estimated)
- Results
- Posted 17 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Venlafaxine | Active comparator | Drug: Venlafaxine50mg of Venlafaxine before sleep |
| Placebo | Placebo comparator | Drug: PlaceboOne piece of placebo before sleep |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Ages 18-70 years
- sleep study (with apnea hypopnea index>5)
- Diagnosis of obstructive sleep apnea
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VenlafaxineVenlafaxine 50mg before sleep | Drug | Venlafaxine |
| PlaceboOne piece of placebo before sleep | Drug | Placebo |
Primary outcome
The Apnea Hypopnea Index
Time frame: 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
Time frame: 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.
3 secondary outcomes
Loop Gain
Time frame: Baseline and 7-day follow up
Arousal Threshold
Time frame: Baseline and 7-day follow up
Sleep Efficiency
Time frame: Baseline and 7-day follow up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23721582Eckert 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.
- Background: PubMed 26715227Carter 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.
- Background: PubMed 26569377Deacon 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.
- Background: PubMed 25321848Edwards 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.
- Background: PubMed 23990246Eckert 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.
- Derived from this study: PubMed 32278781Schmickl 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.
Related trials for Obstructive Sleep Apnea
RecruitingObservational study
Development and Validation of a Multimodal Deep Learning Model Using Peripheral Oxygen Saturation and Ballistocardiography Signals for Predicting Apnea-Hypopnea Index in Obstructive Sleep Apnea
Obstructive Sleep Apnea
RecruitingPhase 3
A Study to Learn About the Monthly Dosing Study Medicine Called Berobenatide in Adults With Breathing Problems During Sleep and Overweight or Obesity Who Do Not Use a Breathing Machine (PAP) (VESPER-OSA 2)
Apnea, Sleep Disorders
Not yet recruitingPhase 2
Supplemental Oxygen for Sleep-Disordered Breathing in Adults With Chronic Opioid Use.
Sleep-disordered Breathing, Chronic Opioid Use
Recruiting
Nightly Wearable Monitoring During Home-Based Submental Electrical Stimulation for Obstructive Sleep Apnea
Obstructive Sleep Apnea
RecruitingPhase 1/2
DRonabinol Treatment of OSA
Obstructive Sleep Apnea
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Venlafaxine in people with Obstructive Sleep Apnea, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Apnea Hypopnea Index (time frame: Baseline and 7-day follow up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02714400, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2020.