Improving 24-hour Blood Pressure in Obstructive Sleep Apnea

Study Overview
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Brief Summary
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This study examines the combined effects of an angiotensin receptor blocker (ARB), antioxidant supplementation, and continuous positive airway pressure (CPAP) therapy on the lowering of 24-hour blood pressure in persons with moderate to severe Obstructive Sleep Apnea (OSA). All participants will undergo CPAP therapy as prescribed by their doctor; however, half of the participants will receive the combined ARB and antioxidant treatment while the other half of the participants will receive a placebo.

Detailed Description
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OSA is a sleep disorder characterized by repetitive collapses (apneas) or partial collapses (hypopneas) of the upper airway. These airway obstructions result in intermittent reductions in arterial oxygen saturation (hypoxia), which causes a reflexive increase in sympathetic activation and systemic vasoconstriction. Resumption of breathing results in transient surges in blood pressure (BP) that can reach as high as 240/130 mm/Hg. OSA effects up to 24% of the adult population and evidence suggests a causal relationship between OSA and cardiovascular disease (CVD) development. While the exact mechanisms are unknown, data from animal and human models suggest that exposure to chronic intermittent hypoxia (IH) plays a significant role in the pathogenesis of cardiovascular comorbidity. Persons with OSA exhibit increased daytime sympathetic activity, markers of oxidative stress, and vasoactive hormones, particularly angiotensin II, that contribute to systemic vasoconstriction. These factors contribute to early endothelial dysfunction and contribute to sustained elevations in BP. While CPAP is the gold standard OSA treatment, adherence rates are low and evidence suggests that treatment does not reduce the rates of CVD in large population-based studies. Telmisartan is a receptor blocker for angiotensin II and not only has BP lowering effects, but also has unique anti-inflammatory properties and beneficial influences on endothelial function. The addition of an antioxidant supplement may increase the reactive oxygen species scavenging capacity and, in combination with ARB treatment, may provide more robust effects on BP in persons with OSA.

Official Title
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Combined Treatment of Angiotensin Receptor Blocker and Antioxidant Supplementation as a Novel Adjunctive Therapy for 24-hour Blood Pressure Improvement in Obstructive Sleep Apnea

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Device: Continuous Positive Airway Pressure CPAP
* Drug: Telmisartan 80mg
* Dietary Supplement: Alpha-Lipoic Acid 600mg
* Other: Microcrystalline Cellulose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Apnea/Hypopnea Index (AHI) greater than/equal to 15 events per hour of sleep No prior use of CPAP Body mass index less than 30kg/m2 Does not take ARBs or angiotensin converting enzyme inhibitors for blood pressure control Females of childbearing potential on an effective or highly effective means of contraception Exclusion Criteria: Prescribed and/or taking the following medications: diuretics (including potassium-sparing diuretics), Digoxin, lithium salts, and/or nonsteroidal anti-inflammatory drugs Over the counter supplements that affect the cardiovascular system, such as fish oils, vitamins, or other antioxidants History of heart failure History of myocardial infarction History of coronary artery disease History of stroke History of diabetes mellitus History of impaired renal function History of chronic obstructive pulmonary disease History of asthma History of central sleep apnea Smoked within the past year Hypotensive (Systolic blood pressure (SBP) <90 mmHg and diastolic blood pressure (DBP) <60 mmHg) Females who do not have a means of contraception, are pregnant, planning to become pregnant, and/or are breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined Treatment<br>Subjects will be given 80 mg/day Telmisartan + 600 mg/day Alpha-Lipoic Acid. Subjects will also be prescribed CPAP therapy by their physician. Subjects will be instructed to use their CPAP device according to their physician's guidelines. | Device: Continuous Positive Airway Pressure CPAP<br>* All subjects will be advised to use their continuous positive airway pressure (CPAP) in accordance to their physician's guidelines.<br>Drug: Telmisartan 80mg<br>* Subjects in this group will receive 80mg/day of Telmisartan (an angiotensin receptor blocker). Treatments will be administered in pre-packaged blister packages. Subjects will take Telmisartan once per day for 6 weeks.<br>Dietary Supplement: Alpha-Lipoic Acid 600mg<br>* Subjects in this group will receive 600mg/day of Alpha-Lipoic Acid (an antioxidant). Treatments will be administered in pre-packaged blister packages. Subjects will take Alpha-Lipoic Acid once per day for 6 weeks.<br>|
| Placebo Comparator: Placebo Control<br>Subjects will be given placebo capsules. Subjects will also be prescribed CPAP therapy by their physician. Subjects will be instructed to use their CPAP device according to their physician's guidelines. | Device: Continuous Positive Airway Pressure CPAP<br>* All subjects will be advised to use their continuous positive airway pressure (CPAP) in accordance to their physician's guidelines.<br>Other: Microcrystalline Cellulose<br>* Subjects in this group will receive two capsules of Microcrystalline Cellulose (placebo). Treatments will be administered in pre-packaged blister packages. Subjects will take placebo pills once per day for 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24-hour blood pressure | Systolic, diastolic, and mean arterial blood pressure (mmHg) | Change from baseline of 24-hour systolic, diastolic, and mean arterial blood pressure at 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Continuous Positive Airway Pressure, 24-hour blood pressure, Telmisartan, Alpha-Lipoic Acid