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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-004866-33 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acetazolamide and CPAP | Active Comparator | Acetazolamide: Diamox®. Hard white capsule, 250 mg. The total treatment is 4 weeks (2+2 weeks). Dosing of acetazolamide will be up-titrated during 3 days according to manufacturer instruction and titration scheme of the study. Maximum dosage (750mg) following titration will be administered as morning (250 mg) and evening(500mg) dosages.Evening medication should be taken 2 hours before bedtime. CPAP: Continuous positive nasal airway pressure (nCPAP) delivers slightly pressurized air throughout the breathing cycle and will be given through a mask that is placed and secured over the person's nose. nCPAP titration will follow clinical routines. The standard setting is a pressure delivery in the pressure range 5-15 mbar. The adequate performance of the device is controlled by user time readers and built-in memory cards and control readings are routinely performed at the end of each treatment regimen. Total duration of CPAP treatment is 4(2+2) weeks. |
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| CPAP | Active Comparator | Continuous positive nasal airway pressure (nCPAP) delivers slightly pressurized air throughout the breathing cycle and will be given through a mask that is placed and secured over the person's nose. nCPAP titration will follow clinical routines whereby the patient is equipped with an autotitrating device (Sullivan S9). The standard setting is a pressure delivery in the pressure range 5-15 mbar and the full treatment is maintained in the patient´s home. The adequate performance of the device is controlled by user time readers and built-in memory cards and control readings are routinely performed at the end of each treatment regimen. Patients will be encouraged via telephone calls for maximum use. Total duration of CPAP treatment is 4(2+2) weeks. |
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| Acetazolamide | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acetazolamide | Drug | Acetazolamide, 250mg tablets, will be administrated as multiple doses. Dosing of acetazolamide will be up-titrated during 3 days according to manufacturer instruction and titration scheme of the study. Maximum daily dosage is 750 mg (equivalent of 3 tablets/daily). Evening medication should be taken 2 hours before bedtime. The total length of Acetazolamide treatment will be 4 weeks (2x2) including 3 days of titration phase of the drug. |
| Measure | Description | Time Frame |
|---|---|---|
| The primary efficacy variable is the reduction in systolic/diastolic office blood pressure (mmHg) between the treatment regimens | The effect will be expressed in terms systolic and diastolic blood pressure (resting office, provoked office and 24 hour). | Baseline to 10 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Secondary objectives include Apnea-hypopnea Index, AHI score in patients with OSA after treatment. | Baseline to 10 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Other outcome measures include the assessment of vascular function. | Vascular function will be assessed by: Cold pressor test: assessing vascular response and pulse excitability. Arteriograph: Standard radial pulse assessment to determine pulse wave and augmentation. Aritmethic stress test: Evaluate cardiovascular responses such as heart rate, blood pressure and heart rate variability induced by mental work. CardioPAT: Finger plethysmograph measuring peripheral arterial tone as well as endothelial function following brachial artery compression (ischemia). Full overnight two channel MC Cardio recorder (Sleep apnea indices and recording of continuous oximetry signal for vascular stiffness, microcirculation and chemosensory vascular responsiveness) Markers of OSA include: |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jan Hedner, MD. Prof. | Dept of internal medicine. Center for Sleep and Vigilance disorders. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Sleep and Vigilance disorders | Gothenburg | Västra Götaland County | 40530 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29510792 | Derived | Eskandari D, Zou D, Grote L, Hoff E, Hedner J. Acetazolamide Reduces Blood Pressure and Sleep-Disordered Breathing in Patients With Hypertension and Obstructive Sleep Apnea: A Randomized Controlled Trial. J Clin Sleep Med. 2018 Mar 15;14(3):309-317. doi: 10.5664/jcsm.6968. |
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Acetazolamide (Diamox®) 250 mg. Hard white capsule. The total length of acetazolamide treatment will be 4 weeks (2x2) including 3 days of titration phase of the drug. Dosing of acetazolamide will be up-titrated during 3 days according to manufacturer instruction and titration scheme of the study. Maximum dosage (750mg) following titration will be administered as morning (250 mg) and evening(500mg)dosages.Evening medication should be taken 2 hours before bedtime. The tablets will be swallowed with 300 ml of water (room temperature) in an upright body position and preferably in connection to a meal. |
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| nasal Continuous Positive Airway Pressure (nCPAP) | Device |
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| Baseline to 10 weeks |
| Markers of OSA such as oxygen desaturation, mean overnight oxygenation, and sleep quality (by polygraphic (PG) assessment, daytime sleepiness, patient-reported outcomes as well as effects on metabolic markers. | Markers of OSA include: Oxygen desaturation (ODI, events/hour), Mean overnight oxygenation (Spo2, %), Daytime sleepiness: Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ). Patient reported outcomes include: Clinical Global rating Impression and Severity (CGI/S), Columbia suicidal severity rating scale (CSSR-S) Metabolic markers include:Total Cholesterol, HDL, LDL, Triglycerides, Insulin, HbA1C, Fasting plasma glucose and cathecholamines. | Baseline to 10 weeks |
| ID | Term |
|---|---|
| D020181 | Sleep Apnea, Obstructive |
| D012891 | Sleep Apnea Syndromes |
| D006973 | Hypertension |
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012893 | Sleep Wake Disorders |
| ID | Term |
|---|---|
| D012140 | Respiratory Tract Diseases |
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009461 | Neurologic Manifestations |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000086 | Acetazolamide |
| D045422 | Continuous Positive Airway Pressure |
| ID | Term |
|---|---|
| D013830 | Thiadiazoles |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011175 | Positive-Pressure Respiration |
| D012121 | Respiration, Artificial |
| D058109 | Airway Management |
| D013812 | Therapeutics |
| D012138 | Respiratory Therapy |
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