Improving 24-hour Blood Pressure in Obstructive Sleep Apnea
Primary Purpose
Obstructive Sleep Apnea
Status
Withdrawn
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Continuous Positive Airway Pressure CPAP
Telmisartan 80mg
Alpha-Lipoic Acid 600mg
Microcrystalline Cellulose
Sponsored by
About this trial
This is an interventional treatment trial for Obstructive Sleep Apnea focused on measuring Telmisartan, Alpha-Lipoic Acid, Continuous Positive Airway Pressure, 24-hour blood pressure
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Combined Treatment
Placebo Control
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Change in 24-hour blood pressure
Systolic, diastolic, and mean arterial blood pressure (mmHg)
Secondary Outcome Measures
Full Information
NCT ID
NCT04021550
First Posted
July 10, 2019
Last Updated
May 17, 2023
Sponsor
University of British Columbia
Collaborators
Heart and Stroke Foundation of Canada, Michael Smith Foundation for Health Research
1. Study Identification
Unique Protocol Identification Number
NCT04021550
Brief Title
Improving 24-hour Blood Pressure in Obstructive Sleep Apnea
Official Title
Combined Treatment of Angiotensin Receptor Blocker and Antioxidant Supplementation as a Novel Adjunctive Therapy for 24-hour Blood Pressure Improvement in Obstructive Sleep Apnea
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Covid-19 Pandemic prevented this study from beginning
Study Start Date
May 2023 (Anticipated)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
December 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of British Columbia
Collaborators
Heart and Stroke Foundation of Canada, Michael Smith Foundation for Health Research
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstructive Sleep Apnea
Keywords
Telmisartan, Alpha-Lipoic Acid, Continuous Positive Airway Pressure, 24-hour blood pressure
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Combined Treatment
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo Control
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Continuous Positive Airway Pressure CPAP
Intervention Description
All subjects will be advised to use their continuous positive airway pressure (CPAP) in accordance to their physician's guidelines.
Intervention Type
Drug
Intervention Name(s)
Telmisartan 80mg
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Alpha-Lipoic Acid 600mg
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Microcrystalline Cellulose
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in 24-hour blood pressure
Description
Systolic, diastolic, and mean arterial blood pressure (mmHg)
Time Frame
Change from baseline of 24-hour systolic, diastolic, and mean arterial blood pressure at 6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
21504246
Citation
Frampton JE. Telmisartan: a review of its use in cardiovascular disease prevention. Drugs. 2011 Apr 16;71(6):651-77. doi: 10.2165/11206710-000000000-00000.
Results Reference
background
PubMed Identifier
29036393
Citation
Khayat RN, Varadharaj S, Porter K, Sow A, Jarjoura D, Gavrilin MA, Zweier JL. Angiotensin Receptor Expression and Vascular Endothelial Dysfunction in Obstructive Sleep Apnea. Am J Hypertens. 2018 Feb 9;31(3):355-361. doi: 10.1093/ajh/hpx174.
Results Reference
background
PubMed Identifier
18807180
Citation
Khayat R, Patt B, Hayes D Jr. Obstructive sleep apnea: the new cardiovascular disease. Part I: Obstructive sleep apnea and the pathogenesis of vascular disease. Heart Fail Rev. 2009 Sep;14(3):143-53. doi: 10.1007/s10741-008-9112-z. Epub 2008 Sep 20.
Results Reference
background
PubMed Identifier
27542595
Citation
Rotenberg BW, Murariu D, Pang KP. Trends in CPAP adherence over twenty years of data collection: a flattened curve. J Otolaryngol Head Neck Surg. 2016 Aug 19;45(1):43. doi: 10.1186/s40463-016-0156-0.
Results Reference
background
PubMed Identifier
20522795
Citation
Pepin JL, Tamisier R, Barone-Rochette G, Launois SH, Levy P, Baguet JP. Comparison of continuous positive airway pressure and valsartan in hypertensive patients with sleep apnea. Am J Respir Crit Care Med. 2010 Oct 1;182(7):954-60. doi: 10.1164/rccm.200912-1803OC. Epub 2010 Jun 3.
Results Reference
background
Learn more about this trial
Improving 24-hour Blood Pressure in Obstructive Sleep Apnea
We'll reach out to this number within 24 hrs