Effect of Selective and Nonselective Cyclooxygenase Enzyme Inhibition on Arterial Blood Pressure and Cerebral Blood Flow With Exposure to Intermittent Hypoxia in Humans

NCT01280006 | Completed Phase 1 DMC

• 1 other identifier: UC-MMHAP-COX-IH-2010001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The study has been designed to assess the effect of cyclooxygenase inhibition on blood pressure, cerebral blood flow, ventilation and renal hemodynamics following chronic intermittent hypoxia exposure.

Conditions

Obstructive Sleep Apnea; Hypertension; Cardiovascular Diseases; Stroke

Keywords

Obstructive Sleep Apnea; Hypoxia; Sleep; Blood Pressure; Hypertension; Myocardial Infarction; Stroke; Ventilation; Brain; Cerebral Blood Flow; Renal Blood Flow

Outcome Measures

Primary Outcomes (2)

• Arterial Blood Pressure

  Blood pressure will be monitored during all three protocols.

  Six weeks

• Cerebral Blood Flow

  The cerebral blood flow will be mesauresed during each testing days of all three protocols.

  Six weeks

Secondary Outcomes (2)

• Ventilatory Response

  Six weeks.

• Renal Hemodynamics

  Six weeks

Interventions

Intermittent hypoxia OTHER

The subjects will receive five days of drug intervention: either non-selective cyclooxygenase (Indomethacin) or selective cyclooxygenase-2 inhibition (Celecoxib) or placebo. On the testing day, the subjects will undergo an acute intermittent hypoxia testing before and six hours of hypoxic chamber exposure mimicking obstructive sleep apnea syndrome.

Indomethacin DRUG

The subjects will receive five days of drug intervention: either non-selective cyclooxygenase (Indomethacin) or selective cyclooxygenase-2 inhibition (Celecoxib) or placebo. Then they will be tested with an exposure of intermittent hypoxia. Indomethacin: 50 mg, Oral, three times per day for five days.

Also known as: Apo-Indomethacin

Celecoxib DRUG

The subjects will receive five days of drug intervention: either non-selective cyclooxygenase (Indomethacin) or selective cyclooxygenase-2 inhibition (Celecoxib) or placebo. Then they will be tested with an exposure of intermittent hypoxia. Celecoxib: 200 mg, Oral, two times per day for five days with a visually matching sequential placebo in between of two doses.

Also known as: Celebrex

Placebo DRUG

The subjects will receive five days of drug intervention: either non-selective cyclooxygenase (Indomethacin) or selective cyclooxygenase-2 inhibition (Celecoxib) or placebo. Then they will be tested with an exposure of intermittent hypoxia. Placebo: Oral, three times per day for five days.

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects
• years of age
• Informed written consent

You may not qualify if:

• Any history of cardio-respiratory diseases, ongoing medication, smoking, trauma, acute illnesses, collagen vascular diseases, rheumatoid arthritis, osteoarthritis

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

The Laboratory of Human Cerebrovascular Physiology, HMRB 209 & HMRB 230, University of Calgary

Calgary, Alberta, T2N 4N1, Canada

Location

Related Publications (1)

• Beaudin AE, Pun M, Yang C, Nicholl DD, Steinback CD, Slater DM, Wynne-Edwards KE, Hanly PJ, Ahmed SB, Poulin MJ. Cyclooxygenases 1 and 2 differentially regulate blood pressure and cerebrovascular responses to acute and chronic intermittent hypoxia: implications for sleep apnea. J Am Heart Assoc. 2014 May 9;3(3):e000875. doi: 10.1161/JAHA.114.000875.

  PMID: 24815497 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Hypertension; Cardiovascular Diseases; Stroke; Hypoxia; Myocardial Infarction; Respiratory Aspiration

Interventions

Indomethacin; Celecoxib

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Myocardial Ischemia; Heart Diseases; Infarction; Ischemia; Pathologic Processes; Necrosis

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Marc J Poulin, PhD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof Dr.

Study Record Dates

• First Submitted: January 18, 2011
• First Posted: January 20, 2011
• Study Start: January 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: December 5, 2011

Record last verified: 2011-12

Locations

CA (1)