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Etiology of Sleep Apnea-related Hyperaldosteronism - BP Treatment

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ClinicalTrials.gov Identifier: NCT01897727
Recruitment Status : Completed
First Posted : July 12, 2013
Results First Posted : January 15, 2014
Last Update Posted : January 15, 2014
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Eric Judd, University of Alabama at Birmingham

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.


Condition or disease Intervention/treatment Phase
Obstructive Sleep Apnea Resistant Hypertension Hyperaldosteronism Drug: Spironolactone Drug: BP medication uptitration Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : January 2009
Actual Primary Completion Date : April 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea

Arm Intervention/treatment
Active Comparator: Spironolactone
Spironolactone 25 mg administered following baseline measurements and uptitrated to 50 mg if BP > 140/90 mm Hg throughout the 3 month study.
Drug: Spironolactone
Sham Comparator: Standard of care BP treatment
Antihypertensive medication added and/or uptitrated to keep BP < 140/90 mm Hg throughout the study.
Drug: BP medication uptitration
antihypertensive medication added or uptitrated following standard of care




Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   19 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01897727


Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
University of Alabama at Birmingham
National Heart, Lung, and Blood Institute (NHLBI)
Publications:
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Responsible Party: Eric Judd, Sub investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01897727    
Other Study ID Numbers: F080821012
R01HL075614 ( U.S. NIH Grant/Contract )
First Posted: July 12, 2013    Key Record Dates
Results First Posted: January 15, 2014
Last Update Posted: January 15, 2014
Last Verified: December 2013
Keywords provided by Eric Judd, University of Alabama at Birmingham:
sleep apnea
hypertension
aldosterone
hyperaldosteronism
spironolactone
blood pressure
resistant
Additional relevant MeSH terms:
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Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Hypertension
Hyperaldosteronism
Vascular Diseases
Cardiovascular Diseases
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases
Spironolactone
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents