Obstructive Sleep ApneaNCT01897727
Etiology of Sleep Apnea-related Hyperaldosteronism - BP Treatment
A study testing Spironolactone and BP medication uptitration in people with Obstructive Sleep Apnea and Resistant Hypertension, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
Hypertension affects an estimated 60-70 million Americans, predisposing them to potentially life threatening cardiovascular complications. Resistant hypertension, defined as uncontrolled blood pressure on 3 or more different antihypertensive agents, is common, affecting 15-20% of the entire hypertensive population or… Read more about this study
- Who is it for?
- Ages 19 to 80 years
- Conditions the study is for
- Obstructive Sleep Apnea, Resistant Hypertension, Hyperaldosteronism
- What is being tested?
- Spironolactone and BP medication uptitration
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to Apr 2012
- Phase
- Interventional
- 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 19 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Resistant hypertension defined as office BP that is uncontrolled with 3 or more antihypertensive medications
- Moderate-severe OSA defined as AHI ≥15 events/hr
- Self-reported adherence >80% with prescribed antihypertensive medications.
Who cannot join
- Ongoing use of a potassium sparing diuretic
- History of congestive heart failure (ejection fraction of <40%)
- Chronic kidney disease (creatinine clearance <60 ml/min)
- History of cardiovascular disease (stroke, TIA, myocardial infarction, or revascularization procedure)
- Known or suspected history of secondary cause of hypertension other than primary aldosteronism
- Severe nocturnal hypoxemia (O2 desaturation nadir <60%)
Show all 11Show fewer
- White coat hypertension defined as office BP >140/90 mm Hg and ambulatory daytime BP <135/85 mm Hg
- Central sleep apnea (defined as 5% or more of the apneas as central apneas) and/or the presence of any Cheyne-Stokes breathing
- Subjects working shift work or having other known circadian rhythm disorders such that their sleep-wake schedule is altered
- Excessive daytime sleepiness as indicated by an Epworth score of >10
- Pregnant Women
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294
About this study
Official title: Randomized Controlled Trial of Spironolactone Versus Standard of Care Blood Pressure Treatment on the Severity of Obstructive Sleep Apnea in Patients With Resistant Hypertension
Hypertension affects an estimated 60-70 million Americans, predisposing them to potentially life threatening cardiovascular complications. Resistant hypertension, defined as uncontrolled blood pressure on 3 or more different antihypertensive agents, is common, affecting 15-20% of the entire hypertensive population or an estimated 12-14 million Americans. Although associated with obesity, increasing age, black race, and chronic kidney disease, mechanisms of treatment resistance remain obscure. The investigators' laboratory identified primary aldosteronism (PA) as a common cause of treatment resistance with a prevalence of 20% among subjects with resistant hypertension. This is clinically important because recognition of PA can lead to effective treatment with use of aldosterone blockers. Obstructive sleep apnea (OSA) is strongly associated with and predicts development of hypertension as demonstrated in landmark cohort studies including the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study.
The investigators' laboratory has confirmed OSA to be extremely common in subjects with resistant hypertension, with a prevalence of approximately 85%. Recognizing that PA and OSA are exceptionally common in subjects with resistant hypertension, the investigators hypothesized that the 2 may be causally related. In testing this hypothesis, the investigators recently reported that plasma aldosterone levels are positively correlated with OSA severity in subjects with resistant hypertension but not in normotensive control subjects. This observation suggests that there is an important mechanistic interaction between untreated OSA and aldosterone excess in subjects with resistant hypertension. While the investigators' original hypothesis was that OSA stimulates aldosterone release, the investigators recognize that the opposite may also be true; that is, aldosterone excess in subjects with resistant hypertension worsens OSA. Distinguishing between these two possibilities has potentially far-reaching clinical implications. If the former hypothesis is true, effective treatment of OSA would be expected to suppress aldosterone release in subjects with resistant hypertension, thereby reversing the underlying cause of their treatment resistance. If the latter hypothesis is true, use of mineralocorticoid receptor antagonists would be expected to reduce OSA severity in subjects with resistant hypertension, thereby enhancing treatment of OSA. Either scenario would represent a new treatment approach for a highly prevalent and serious medical problem.
- Being tested
- Spironolactone, BP medication uptitration
- Keywords
- sleep apnea, hypertension, aldosterone, hyperaldosteronism, spironolactone, blood pressure, resistant
- Medical subject headings
- Sleep Apnea, Obstructive, Hyperaldosteronism, Sleep Apnea Syndromes, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SpironolactoneDrug
BP medication uptitrationDrug
antihypertensive medication added or uptitrated following standard of care
| Study group | Role | What they receive |
|---|---|---|
| Spironolactone | Active comparator | Spironolactone 25 mg administered following baseline measurements and uptitrated to 50 mg if BP > 140/90 mm Hg throughout the 3 month study. Receives: Drug: Spironolactone |
| Standard of care BP treatment | Sham comparator | Antihypertensive medication added and/or uptitrated to keep BP < 140/90 mm Hg throughout the study. Receives: Drug: BP medication uptitration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severity of Obstructive Sleep Apnea
3 month change in apnea-hypopnea index assessed by diagnostic, full-night polysomnography. AHI values are typically categorized as 5-15/hr = mild; 15-30/hr = moderate; and > 30/h = severe.
Measured: baseline and 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2013 (estimated)
- Study startJan 2009
- Primary completionApr 2012
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 (1)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 Alabama at BirminghamThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Eric Judd, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01897727
- Sponsor's protocol ID
- F080821012
- Other IDs
- R01HL075614
- Status last verified
- Dec 2013
- First submitted
- 9 Jul 2013
- Last updated
- 15 Jan 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Gaddam K, Pimenta E, Thomas SJ, Cofield SS, Oparil S, Harding SM, Calhoun DA. Spironolactone reduces severity of obstructive sleep apnoea in patients with resistant hypertension: a preliminary report. J Hum Hypertens. 2010 Aug;24(8):532-7. doi: 10.1038/jhh.2009.96. Epub 2009 Dec 17.
PubMed 20016520
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial of Spironolactone Versus Standard of Care Blood Pressure Treatment on the Severity of Obstructive Sleep Apnea in Patients With Resistant Hypertension
- ClinicalTrials.gov ID
- NCT01897727
- Acronym / sponsor ID
- F080821012
- Keywords
- sleep apnea, hypertension, aldosterone, hyperaldosteronism, spironolactone, blood pressure, resistant
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jan 2009
- Primary completion
- Apr 2012 (actual)
- First posted
- 12 Jul 2013 (estimated)
- Results
- Posted 15 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hypertension affects an estimated 60-70 million Americans, predisposing them to potentially life threatening cardiovascular complications. Resistant hypertension, defined as uncontrolled blood pressure on 3 or more different antihypertensive agents, is common, affecting 15-20% of the entire hypertensive population or an estimated 12-14 million Americans. Although associated with obesity, increasing age, black race, and chronic kidney disease, mechanisms of treatment resistance remain obscure. The investigators' laboratory identified primary aldosteronism (PA) as a common cause of treatment resistance with a prevalence of 20% among subjects with resistant hypertension. This is clinically important because recognition of PA can lead to effective treatment with use of aldosterone blockers. Obstructive sleep apnea (OSA) is strongly associated with and predicts development of hypertension as demonstrated in landmark cohort studies including the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study.
The investigators' laboratory has confirmed OSA to be extremely common in subjects with resistant hypertension, with a prevalence of approximately 85%. Recognizing that PA and OSA are exceptionally common in subjects with resistant hypertension, the investigators hypothesized that the 2 may be causally related. In testing this hypothesis, the investigators recently reported that plasma aldosterone levels are positively correlated with OSA severity in subjects with resistant hypertension but not in normotensive control subjects. This observation suggests that there is an important mechanistic interaction between untreated OSA and aldosterone excess in subjects with resistant hypertension. While the investigators' original hypothesis was that OSA stimulates aldosterone release, the investigators recognize that the opposite may also be true; that is, aldosterone excess in subjects with resistant hypertension worsens OSA. Distinguishing between these two possibilities has potentially far-reaching clinical implications. If the former hypothesis is true, effective treatment of OSA would be expected to suppress aldosterone release in subjects with resistant hypertension, thereby reversing the underlying cause of their treatment resistance. If the latter hypothesis is true, use of mineralocorticoid receptor antagonists would be expected to reduce OSA severity in subjects with resistant hypertension, thereby enhancing treatment of OSA. Either scenario would represent a new treatment approach for a highly prevalent and serious medical problem.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Spironolactone | Active comparator | Drug: SpironolactoneSpironolactone 25 mg administered following baseline measurements and uptitrated to 50 mg if BP > 140/90 mm Hg throughout the 3 month study. |
| Standard of care BP treatment | Sham comparator | Drug: BP medication uptitrationAntihypertensive medication added and/or uptitrated to keep BP < 140/90 mm Hg throughout the study. |
Who may qualify
- Ages
- 19 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Resistant hypertension defined as office BP that is uncontrolled with 3 or more antihypertensive medications
- Moderate-severe OSA defined as AHI ≥15 events/hr
- Self-reported adherence >80% with prescribed antihypertensive medications.
Key exclusion criteria (11 listed)
- Ongoing use of a potassium sparing diuretic
- History of congestive heart failure (ejection fraction of <40%)
- Chronic kidney disease (creatinine clearance <60 ml/min)
- History of cardiovascular disease (stroke, TIA, myocardial infarction, or revascularization procedure)
- Known or suspected history of secondary cause of hypertension other than primary aldosteronism
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 |
|---|---|---|
| Spironolactone | Drug | Spironolactone |
| BP medication uptitrationantihypertensive medication added or uptitrated following standard of care | Drug | Standard of care BP treatment |
Primary outcome
Severity of Obstructive Sleep Apnea
Time frame: baseline and 3 months
3 month change in apnea-hypopnea index assessed by diagnostic, full-night polysomnography. AHI values are typically categorized as 5-15/hr = mild; 15-30/hr = moderate; and > 30/h = severe.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20016520Gaddam K, Pimenta E, Thomas SJ, Cofield SS, Oparil S, Harding SM, Calhoun DA. Spironolactone reduces severity of obstructive sleep apnoea in patients with resistant hypertension: a preliminary report. J Hum Hypertens. 2010 Aug;24(8):532-7. doi: 10.1038/jhh.2009.96. Epub 2009 Dec 17.
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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.
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 study testing Spironolactone and BP medication uptitration in people with Obstructive Sleep Apnea and Resistant Hypertension, run by University of Alabama at Birmingham 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 11 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 15 Jan 2014. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jan 2014). 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?
Severity of Obstructive Sleep Apnea (time frame: baseline and 3 months). 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 NCT01897727, which also lists 1 linked publication.
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 15 Jan 2014; AzTrials last refreshed its copy on 8 Nov 2026.