Etiology of Sleep Apnea-related Hyperaldosteronism - BP Treatment

NCT ID: NCT01897727

Last Updated: 2014-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31

Brief 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 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.

Conditions

Obstructive Sleep Apnea; Resistant Hypertension; Hyperaldosteronism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Spironolactone

Spironolactone 25 mg administered following baseline measurements and uptitrated to 50 mg if BP \> 140/90 mm Hg throughout the 3 month study.

Group Type: ACTIVE_COMPARATOR

Spironolactone

Intervention Type: DRUG

Standard of care BP treatment

Antihypertensive medication added and/or uptitrated to keep BP \< 140/90 mm Hg throughout the study.

Group Type: SHAM_COMPARATOR

BP medication uptitration

Intervention Type: DRUG

antihypertensive medication added or uptitrated following standard of care

Interventions

Spironolactone

Intervention Type: DRUG

BP medication uptitration

antihypertensive medication added or uptitrated following standard of care

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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%)
• 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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Eric Judd

Sub investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 20016520 (View on PubMed)

Other Identifiers

R01HL075614

Identifier Type: NIH

Identifier Source: secondary_id

View Link

F080821012

Identifier Type: -

Identifier Source: org_study_id