A Short Term Open, Randomized Cross-over Trial Exploring the Effect of Carbonic Anhydrase Inhibition by Acetazolamide on Sleep Apnea Associated Hypertension and Vascular Dysfunction
Information source: Göteborg University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Obstructive Sleep Apnea; Sleep-Disordered Breathing; Blood Pressure; Hypertension
Intervention: Acetazolamide (Drug); nasal Continuous Positive Airway Pressure (nCPAP) (Device)
Phase: Phase 2
Status: Recruiting
Sponsored by: Göteborg University Official(s) and/or principal investigator(s):
Jan Hedner, MD. Prof., Principal Investigator, Affiliation: Dept of internal medicine. Center for Sleep and Vigilance disorders.
Overall contact:
Davoud Eskandari, Msc, Phd-student, Phone: +46 31 342 37 41, Email: davoud.eskandari@lungall.gu.se
Summary
This is a short term open, randomized cross over trial to explore and compare the efficacy
of pharmacological carbonic anhydrase (CA) inhibition on obstructive sleep apnea (OSA)
related hypertension. Patients will be randomized to receive Acetazolamide(Diamox®)(ACZ),
Continuous Positive Airway Pressure (CPAP)or CPAP plus ACZ for 2 weeks. Following a 2 week
wash-out period all study participants will receive the alternative treatment regimen. The
total length of the study will be 10 weeks. The effects of carbonic anhydrase inhibition on
blood pressure,hemodynamics and sleep apnea will be investigated.
Study hypothesis:
Carbonic anhydrase inhibition alone or in combination with nCPAP will prominently reduce
blood pressure in patients with OSA. Further it is hypothesized that CA inhibition will
induce a direct pharmacological effects on vascular stiffness as evidenced in overnight
non-invasive assessments of vascular stiffness and that this effect will be particularly
strong in patients also responding with a reduction of blood pressure.
Clinical Details
Official title: A Short Term Open, Randomized Cross Over Trial Trial Exploring the Effect of Carbonic Anhydrase Inhibition by Acetazolamide on Sleep Apnea Associated Hypertension
Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The primary efficacy variable is the reduction in systolic/diastolic office blood pressure (mmHg) between the treatment regimens
Secondary outcome: The secondary objective is to investigate the direct effect of CA inhibition on sleep disordered breathing (Apnea-hypopnea Index, AHI score (events/hour) in the subgroup of patients with OSA after treatment
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Male.
Criteria:
Inclusion Criteria:
- Provision of informed consent prior to any study specific procedures
- Males 18 to 75 years
- An Apnea-Hypopnea Index (AHI)>15 and an Epworth Sleepiness Scale score (ESS)>6 as
verified by a PSG recording.
- Patients with established hypertension (systolic/diastolic blood pressure >= 160/95,
either systolic or diastolic accounted for).
- Clinically normal physical findings and laboratory values, as judged by the
investigator
- Body mass index >= 35 kg/m2
Exclusion Criteria:
- Hypersensitivity to sulfonamides or acetazolamide-
- Patients with ongoing medication with other sulphonamides or patients any specific
antihypertensive treatment.
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity.
- Subjects with a seizure disorder
- Patients with clinically verified central sleep apnea
- Clinically significant renal (serum creatinine >2. 0 mg/dL or >130 micromol/L),
neurological, metabolic (e. g. Type 1 or 2 diabetes), haematological or hepatic
disease (ASAT or ALAT >2 times the upper limit of normal).
- Subjects with an occupational risk potentially exaggerated by daytime sleepiness such
as handling complex machinery or professional driving
- Unstable angina pectoris, unstable hypertension (or poorly controlled diabetes (HbA1C
< 52 mmoles/mol, or fasting plasma glucose >7 mmoles/l).
- Clinically significant congestive heart failure.
- Myocardial infarction or coronary vessel intervention within the previous 6 months
period.
- Subjects with uncontrolled hypertension (defined as a diastolic blood pressure ≥110
mmHg and/or a systolic blood pressure ≥180 mmHg with or without medication).
- Previously diagnosed or treated clinically significant cardiac arrhythmia
- Clinically significant chronic pulmonary or gastrointestinal disease.
- Clinical history of depression as judged by the investigator or other previous or
present clinically significant psychiatric disease
- Suspected or confirmed poor compliance
- Alcohol or drug abuse during the last year.
- Subjects with any other significant condition that, in the opinion of the
investigator, could interfere with participation in the study.
- Severe nocturnal hypoxia defined as more than 10 episodes with an oxygen desaturation
exceeding 50% or signs of lacking resaturation between desaturations on previous
recordings according to investigators judgment
- Participation in another clinical study during the last 6 months.
- Inability to understand and complete the questionnaires.
Locations and Contacts
Davoud Eskandari, Msc, Phd-student, Phone: +46 31 342 37 41, Email: davoud.eskandari@lungall.gu.se
Center for Sleep and Vigilance disorders, Gothenburg, Vastra Gotaland 40530, Sweden; Recruiting
Davoud Eskandari, Msc, Phd-stud., Phone: +46 31 342 37 41, Email: davoud.eskandari@lungall.gu.se
Jan Hedner, MD.Prof., Principal Investigator
Additional Information
Starting date: March 2014
Last updated: August 10, 2015
|
