Sleep Apnea SyndromesNCT02725632
Sodium Channel Splicing in Obstructive Sleep Apnea (SOCS-OSA)
A study testing CPAP in people with Sleep Apnea Syndromes, run by Rhode Island Hospital at 1 site in United States.
Trial summary
This study is designed to test whether SCN5A mRNA processing is altered in OSA patients, which may contribute to their increased arrhythmic risk, and whether processing of SCN5A mRNA is modulated by CPAP treatment. Specific aims: 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sleep Apnea Syndromes
- What is being tested?
- CPAP
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2015to Mar 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- OSA Eligibility Criteria:
- Age greater than 18 years
- Able to provide informed consent
- New diagnosis of OSA by polysomnogram
- Agree with CPAP treatment
- Control Eligibility Criteria:
Show all 9Show fewer
- Age greater than 18 years
- Without OSA
- Able to provide informed consent
Who cannot join
- Not able to give informed consent due to psychological incapacity
- Chronic use of hypnotics for more than 6 weeks
- Current drug or alcohol addiction
- Rhythm other than sinus at enrollment
- Mandatory and biventricular pacing
- History of heart transplant or left ventricular assist device (LVAD)
Show all 15Show fewer
- Active use of intravenous vasodilators, vasopressors or inotropes
- Hemodialysis or peritoneal dialysis
- Active infection including bacteremia
- Acute coronary syndrome (ACS) within 6 weeks
- Major trauma or surgery within 6 weeks
- Malignant neoplastic disease on active treatment including chemotherapy and radiation therapy, or life expectancy less than 1 year
- Collagen vascular disease on active treatment including steroids and other immunomodulating drugs
- Systemic steroid use within 6 weeks
- Concomitant use of investigational drug within 6 weeks
Trial locations and contacts
1 site in 1 country.
United States1 site
Brown University, Lifespan
Providence, Rhode Island, 02903
About this study
This study is designed to test whether SCN5A mRNA processing is altered in OSA patients, which may contribute to their increased arrhythmic risk, and whether processing of SCN5A mRNA is modulated by CPAP treatment.
Specific aims:
- Compare sodium channel splicing variants in mild, moderate, or severe OSA patients at baseline to at 1 month after CPAP treatment. In addition, the baseline splicing variants of SCN5A in the OSA patients will be compared to an age-matched control group.
- Hypoxia-associated upstream regulators of SCN5a mRNA splicing, Hypoxia-inducible factor 1-alpha (HIF-1α), RNA Binding Motif Protein 25 (RBM25) and LUC7-Like 3 Pre-MRNA Splicing Factor (LUC7L3), will be examined in OSA patients before and after 1 month of CPAP treatment.
Read the detailed description
BACKGROUND \& SIGNIFICANCE Obstructive sleep apnea (OSA) is a common disease with an estimated prevalence of 3% to 7%. It is characterized by recurrent episodes of partial or complete collapse of the upper airway during sleep, resulting in hypopneas or apneas, respectively. The collapse of upper airway during obstructed events result in intermittent hypoxia, recurrent arousals from sleep, metabolic disturbance and poor quality of life. Cardiac arrhythmias are reportedly more frequent in patients with OSA and increase with the number of apneic episodes and the severity of the associated hypoxemia. Recent data from the Sleep Heart Health Study suggested that those with severe sleep disorders had a 2- to 4-fold-higher risk of nocturnal complex arrhythmias. Even after adjustment for age, sex, BMI, and prevalent coronary artery disease, patients with sleep disorders had increased likelihoods of atrial fibrillation, nonsustained ventricular tachycardia, and complex ventricular ectopy.
Continuous positive airway pressure (CPAP) is the first-line treatment for patients with OSA and acts as a pneumatic splint to the upper airway during sleep and corrects the obstruction, improving daytime sleepiness and quality of life. Observational studies suggest that CPAP treatment reduces the incidence of cardiovascular events in patients with moderate and sever OSA.
Sodium channel is an integral membrane protein that plays a central role in conduction of the cardiac impulse in myocytes and cells of the His-Purkinje system. It is a multimeric complex consisting of an α and an auxiliary β-subunit. The α subunit, SCN5A is sufficient to express a functional channel. However, β subunit co-expression increases the level of channel expression and alters the voltage dependence of inactivation. Mutations of the sodium channel result in type 3 long QT syndrome (LQT3), Brugada syndrome, atrial fibrillation, congenital sick sinus syndrome, multifocal premature ventricular contractions (PVCs), and dilated cardiomyopathy.
Recently, the investigators have discovered abnormal sodium channel messenger RNA (mRNA) processing in congestive heart failure (CHF) that results in reduced sodium channel to a range known to be associated with sudden cardiac death. Three truncated SCN5A mRNA splicing variants were identified (denoted variant B (E28B), variant C (E28C), and variant D (E28D)). Among them, E28C and E28D abundances were increased 14.2 fold and 3.8 fold respectively in CHF patients compared to controls. The full length SCN5A mRNA (E28A) was decreased by 24.7% in patients with CHF compared to control. Moreover, a key transcriptional regulatory molecule in hypoxia, hypoxia-induced factor 1α (HIF-1α), and hypoxia-induced mRNA splicing factors, such as RBM25 and LUC7L3, were elevated in human CHF tissue and mediated in vitro truncation of SCN5A mRNA.
Thus, this study is designed to test whether SCN5A mRNA processing is altered in OSA patients, which may contribute to their increased arrhythmic risk, and whether processing of SCN5A mRNA is modulated by CPAP treatment.
SPECIFIC AIMS
- Compare sodium channel splicing variants in mild, moderate, or severe OSA patients at baseline to at 1 month after CPAP treatment. In addition, the baseline splicing variants of SCN5A in the OSA patients will be compared to an age-matched control group.
- Hypoxia-associated upstream regulators of SCN5a mRNA splicing, HIF-1α, RBM25 and LUC7L3, will be examined in OSA patients before and after 1 month of CPAP treatment.
- Conditions
- Sleep Apnea Syndromes
- Being tested
- CPAP
- Keywords
- Sodium channel, splicing variant, sleep apnea syndrome
- Medical subject headings
- Sleep Apnea Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CPAPDevice
The patients on CPAP treatment will be followed-up for 1 month.
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | An age-matched control group will be enrolled and consented. A Data Collection Sheet will be used to document data from the subject's medical records including history, physical exam, active medications, laboratory data, polysomnogram, electrocardiogram, echocardiography and cardiac catheterization. At the time of enrollment, one blood drawn through peripheral venipuncture will be collected. Another blood drawn will be collected after one month. The blood samples will be processed and analyzed to assess for levels of SCN5A mRNA splicing variants. |
| OSA | Active comparator | Newly diagnosed OSA patients will be enrolled and consented. A Data Collection Sheet will be used to document data from the patient's medical records including history, physical exam, active medications, laboratory data, polysomnogram, electrocardiogram, echocardiography and cardiac catheterization.
At the time of enrollment, one blood drawn through peripheral venipuncture will be collected. The patients on CPAP treatment will be followed-up for 1 month. Another blood drawn will be collected after one month of CPAP treatment. The blood samples will be processed and analyzed to assess for levels of SCN5A mRNA splicing variants. Receives: Device: CPAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
The levels of sodium channel splicing variants that are related to the severity of OSA, change from baseline to one month after CPAP treatment.
Measured: Four weeks
Secondary outcomes (1)
The levels of potassium channels that are related to the severity of OSA, change from baseline to one month after CPAP treatment.
Measured: Four weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2016 (estimated)
- Study startAug 2015
- Primary completionMar 2017
- Study completionMar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Sleep Apnea SyndromesStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rhode Island Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Illinois Chicago
- Responsible party
- Sponsor
- Investigators
- Richard Millman, MD, Principal investigator, Rhode Island Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02725632
- Sponsor's protocol ID
- 411013
- Status last verified
- Apr 2017
- First submitted
- 14 Mar 2016
- Last updated
- 26 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Hunt SA; American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol. 2005 Sep 20;46(6):e1-82. doi: 10.1016/j.jacc.2005.08.022. No abstract available.
PubMed 16168273Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell C, Roger V, Sorlie P, Steinberger J, Thom T, Wilson M, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008 Jan 29;117(4):e25-146. doi: 10.1161/CIRCULATIONAHA.107.187998. Epub 2007 Dec 17. No abstract available.
PubMed 18086926Kannel WB, Plehn JF, Cupples LA. Cardiac failure and sudden death in the Framingham Study. Am Heart J. 1988 Apr;115(4):869-75. doi: 10.1016/0002-8703(88)90891-5.
PubMed 3354416
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sodium Channel Splicing in Obstructive Sleep Apnea (SOCS-OSA)
- ClinicalTrials.gov ID
- NCT02725632
- Acronym / sponsor ID
- 411013
- Conditions
- Sleep Apnea Syndromes
- Keywords
- Sodium channel, splicing variant, sleep apnea syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Rhode Island HospitalUniversity, hospital or other
- Collaborators
- University of Illinois Chicago
- Study start
- Aug 2015
- Primary completion
- Mar 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 1 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to test whether SCN5A mRNA processing is altered in OSA patients, which may contribute to their increased arrhythmic risk, and whether processing of SCN5A mRNA is modulated by CPAP treatment.
Specific aims:
- Compare sodium channel splicing variants in mild, moderate, or severe OSA patients at baseline to at 1 month after CPAP treatment. In addition, the baseline splicing variants of SCN5A in the OSA patients will be compared to an age-matched control group.
- Hypoxia-associated upstream regulators of SCN5a mRNA splicing, Hypoxia-inducible factor 1-alpha (HIF-1α), RNA Binding Motif Protein 25 (RBM25) and LUC7-Like 3 Pre-MRNA Splicing Factor (LUC7L3), will be examined in OSA patients before and after 1 month of CPAP treatment.
Detailed description
BACKGROUND \& SIGNIFICANCE Obstructive sleep apnea (OSA) is a common disease with an estimated prevalence of 3% to 7%. It is characterized by recurrent episodes of partial or complete collapse of the upper airway during sleep, resulting in hypopneas or apneas, respectively. The collapse of upper airway during obstructed events result in intermittent hypoxia, recurrent arousals from sleep, metabolic disturbance and poor quality of life. Cardiac arrhythmias are reportedly more frequent in patients with OSA and increase with the number of apneic episodes and the severity of the associated hypoxemia. Recent data from the Sleep Heart Health Study suggested that those with severe sleep disorders had a 2- to 4-fold-higher risk of nocturnal complex arrhythmias. Even after adjustment for age, sex, BMI, and prevalent coronary artery disease, patients with sleep disorders had increased likelihoods of atrial fibrillation, nonsustained ventricular tachycardia, and complex ventricular ectopy.
Continuous positive airway pressure (CPAP) is the first-line treatment for patients with OSA and acts as a pneumatic splint to the upper airway during sleep and corrects the obstruction, improving daytime sleepiness and quality of life. Observational studies suggest that CPAP treatment reduces the incidence of cardiovascular events in patients with moderate and sever OSA.
Sodium channel is an integral membrane protein that plays a central role in conduction of the cardiac impulse in myocytes and cells of the His-Purkinje system. It is a multimeric complex consisting of an α and an auxiliary β-subunit. The α subunit, SCN5A is sufficient to express a functional channel. However, β subunit co-expression increases the level of channel expression and alters the voltage dependence of inactivation. Mutations of the sodium channel result in type 3 long QT syndrome (LQT3), Brugada syndrome, atrial fibrillation, congenital sick sinus syndrome, multifocal premature ventricular contractions (PVCs), and dilated cardiomyopathy.
Recently, the investigators have discovered abnormal sodium channel messenger RNA (mRNA) processing in congestive heart failure (CHF) that results in reduced sodium channel to a range known to be associated with sudden cardiac death. Three truncated SCN5A mRNA splicing variants were identified (denoted variant B (E28B), variant C (E28C), and variant D (E28D)). Among them, E28C and E28D abundances were increased 14.2 fold and 3.8 fold respectively in CHF patients compared to controls. The full length SCN5A mRNA (E28A) was decreased by 24.7% in patients with CHF compared to control. Moreover, a key transcriptional regulatory molecule in hypoxia, hypoxia-induced factor 1α (HIF-1α), and hypoxia-induced mRNA splicing factors, such as RBM25 and LUC7L3, were elevated in human CHF tissue and mediated in vitro truncation of SCN5A mRNA.
Thus, this study is designed to test whether SCN5A mRNA processing is altered in OSA patients, which may contribute to their increased arrhythmic risk, and whether processing of SCN5A mRNA is modulated by CPAP treatment.
SPECIFIC AIMS
- Compare sodium channel splicing variants in mild, moderate, or severe OSA patients at baseline to at 1 month after CPAP treatment. In addition, the baseline splicing variants of SCN5A in the OSA patients will be compared to an age-matched control group.
- Hypoxia-associated upstream regulators of SCN5a mRNA splicing, HIF-1α, RBM25 and LUC7L3, will be examined in OSA patients before and after 1 month of CPAP treatment.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –An age-matched control group will be enrolled and consented. A Data Collection Sheet will be used to document data from the subject's medical records including history, physical exam, active medications, laboratory data, polysomnogram, electrocardiogram, echocardiography and cardiac catheterization. At the time of enrollment, one blood drawn through peripheral venipuncture will be collected. Another blood drawn will be collected after one month. The blood samples will be processed and analyzed to assess for levels of SCN5A mRNA splicing variants. |
| OSA | Active comparator | Device: CPAPNewly diagnosed OSA patients will be enrolled and consented. A Data Collection Sheet will be used to document data from the patient's medical records including history, physical exam, active medications, laboratory data, polysomnogram, electrocardiogram, echocardiography and cardiac catheterization. At the time of enrollment, one blood drawn through peripheral venipuncture will be collected. The patients on CPAP treatment will be followed-up for 1 month. Another blood drawn will be collected after one month of CPAP treatment. The blood samples will be processed and analyzed to assess for levels of SCN5A mRNA splicing variants. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age greater than 18 years
- Able to provide informed consent
- New diagnosis of OSA by polysomnogram
- Agree with CPAP treatment
- Age greater than 18 years
Key exclusion criteria (15 listed)
- Not able to give informed consent due to psychological incapacity
- Chronic use of hypnotics for more than 6 weeks
- Current drug or alcohol addiction
- Rhythm other than sinus at enrollment
- Mandatory and biventricular pacing
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 |
|---|---|---|
| CPAPThe patients on CPAP treatment will be followed-up for 1 month. | Device | OSA |
Primary outcome
The levels of sodium channel splicing variants that are related to the severity of OSA, change from baseline to one month after CPAP treatment.
Time frame: Four weeks
1 secondary outcome
The levels of potassium channels that are related to the severity of OSA, change from baseline to one month after CPAP treatment.
Time frame: Four weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2017.
- Background: PubMed 16168273Hunt SA; American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol. 2005 Sep 20;46(6):e1-82. doi: 10.1016/j.jacc.2005.08.022. No abstract available.
- Background: PubMed 18086926Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell C, Roger V, Sorlie P, Steinberger J, Thom T, Wilson M, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008 Jan 29;117(4):e25-146. doi: 10.1161/CIRCULATIONAHA.107.187998. Epub 2007 Dec 17. No abstract available.
- Background: PubMed 3354416Kannel WB, Plehn JF, Cupples LA. Cardiac failure and sudden death in the Framingham Study. Am Heart J. 1988 Apr;115(4):869-75. doi: 10.1016/0002-8703(88)90891-5.
- Individual participant dataSharing planned: No
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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.
Richard Millman, MD principal investigator
Rhode Island Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CPAP in people with Sleep Apnea Syndromes, run by Rhode Island Hospital 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 9 inclusion and 15 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 26 Apr 2017. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 levels of sodium channel splicing variants that are related to the severity of OSA, change from baseline to one month after CPAP treatment. (time frame: Four weeks). 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 NCT02725632, which also lists 3 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 26 Apr 2017.