Effects of Nebivolol Versus Carvedilol on Cardiopulmonary Function at High Altitude in Healthy Subjects. - Full Text View

Purpose

Exposure of healthy subjects to high altitude hypoxia elicits changes in cardiovascular, respiratory and metabolic features as weel as in exercise performance similar, for some aspects, to those observed in chronic heart failure. Exposure to high altitude hypoxia represents a suitable model to assess different treatments proposed for this pathological condition. Our aim was to evaluate the impact of two different third-generation beta-blockers used in heart failure (carvedilol and nebivolol) on cardiovascular, respiratory, metabolic profile and on exercise performance at high altitude.

Condition	Intervention	Phase
Hypoxia Altitude Heart Failure	Drug: placebo Drug: Carvedilol Drug: Nebivolol	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Comparison of the Cardiovascular, Metabolic and Respiratory Effects of Nebivolol and Carvedilol at High Altitude in Healthy Subjects.

Resource links provided by NLM:

MedlinePlus related topics: Exercise and Physical Fitness Heart Failure Oxygen Therapy

Drug Information available for: Carvedilol Nebivolol Nebivolol Hydrochloride

U.S. FDA Resources

Further study details as provided by Istituto Auxologico Italiano:

Primary Outcome Measures:

Peak Exercise Oxygen Consumption [ Time Frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment. ] [ Designated as safety issue: No ]
Delta Peak Exercise Oxygen Consumption Time 1 Versus Time 3 [ Time Frame: Time 1: sea level, baseline, no treatment. Time 3: within the first two days of high altitude exposure, under treatment. ] [ Designated as safety issue: No ]
Peak Exercise Minute Ventilation [ Time Frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment. ] [ Designated as safety issue: No ]
Delta Peak Exercise Minute Ventilation Time 1 Versus Time 3. [ Time Frame: Time 1: sea level, baseline, no treatment. Time 3: within the first two days of high altitude exposure, under treatment. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Peak Exercise Oxygen Saturation [ Time Frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment. ] [ Designated as safety issue: No ]
Systolic Pulmonary Artery Pressure. [ Time Frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment. ] [ Designated as safety issue: No ]
Resting Energy Expenditure [ Time Frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment. ] [ Designated as safety issue: No ]
Sitting Blood Pressure and Heart Rate [ Time Frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment. ] [ Designated as safety issue: No ]
Mean 24 Hour/Daytime/Night-time Blood Pressure and Heart Rate [ Time Frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment. ] [ Designated as safety issue: No ]

Enrollment:	27
Study Start Date:	May 2006
Study Completion Date:	November 2006
Primary Completion Date:	November 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: placebo Placebo tablets. One tablet twice daily.	Drug: placebo placebo tablet BID
Active Comparator: 2: Carvedilol Carvedilol 25 mg tablets. One tablet twice daily.	Drug: Carvedilol Carvedilol 25 mg tablets. One tablet twice daily.
Active Comparator: 3: Nebivolol Nebivolol 5 mg tablets. One nebivolo tablet daily. One placebo tablet daily.	Drug: Nebivolol nebivolol 5 mg tablets. One nebivolol tablet daily. One placebo tablet daily.

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria

Men or women of any racial background
healthy
sealevel resident
age >= 18 years, =< 65 years
SBP< 130 mmHg and DBP< 80 mmHg, average of two measures at the sceening visit
FG < 100 mg/dl (5.6 mmol/l)
BMI < 25
written informed consent signed

Exclusion Criteria

engagement in regular exercise training
smoking habit
being enrolled in another research study
any current or previous cardiovascular, metabolic disease or any other cronic disease
any current treatment for any medical condition
any medical condition preventing or contraindication exposure to altitude hypoxia
any gastrointestinal disorder interfering with drug absorption
known allergy or contraindications to beta-blockers
pregnant or lactating women; women in reproductive age not using recognized contraceptive methods.
malignancy within the last 5 years
drug abuse or alcohol abuse within the last 5 years
history of noncompliance to medical regimens
incapacity or unwillingness to sign the informed consent
participation in any investigational clinical trial within the last 3 months

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00924833

Locations

Italy
Laboratorio Ricerche Cardiologiche. Istituto Auxologico Italiano. Ospedale S. Luca. Via Spagnoletto, 3. Regina Margherita Hut (Monte Rosa, Italian Alps, 4559 m)
Milan, Italy, 20148

Sponsors and Collaborators

Istituto Auxologico Italiano

Menarini Group

More Information

Publications:

Modesti PA, Vanni S, Morabito M, Modesti A, Marchetta M, Gamberi T, Sofi F, Savia G, Mancia G, Gensini GF, Parati G. Role of endothelin-1 in exposure to high altitude: Acute Mountain Sickness and Endothelin-1 (ACME-1) study. Circulation. 2006 Sep 26;114(13):1410-6. Epub 2006 Sep 18.

Agostoni P, Contini M, Magini A, Apostolo A, Cattadori G, Bussotti M, Veglia F, Andreini D, Palermo P. Carvedilol reduces exercise-induced hyperventilation: A benefit in normoxia and a problem with hypoxia. Eur J Heart Fail. 2006 Nov;8(7):729-35. Epub 2006 Mar 13.

Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Erdine S, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Lindholm LH, Viigimaa M, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O'Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Waeber B, Williams B; Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007 Jun;25(6):1105-87. No abstract available. Erratum in: J Hypertens. 2007 Aug;25(8):1749.

O'Brien E, Asmar R, Beilin L, Imai Y, Mancia G, Mengden T, Myers M, Padfield P, Palatini P, Parati G, Pickering T, Redon J, Staessen J, Stergiou G, Verdecchia P; European Society of Hypertension Working Group on Blood Pressure Monitoring. Practice guidelines of the European Society of Hypertension for clinic, ambulatory and self blood pressure measurement. J Hypertens. 2005 Apr;23(4):697-701. No abstract available.

Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise J, Solomon S, Spencer KT, St John Sutton M, Stewart W; American Society of Echocardiography's Nomenclature and Standards Committee; Task Force on Chamber Quantification; American College of Cardiology Echocardiography Committee; American Heart Association; European Association of Echocardiography, European Society of Cardiology. Recommendations for chamber quantification. Eur J Echocardiogr. 2006 Mar;7(2):79-108. Epub 2006 Feb 2. Review.

Task Force of the Italian Working Group on Cardiac Rehabilitation Prevention; Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology; Piepoli MF, Corrà U, Agostoni PG, Belardinelli R, Cohen-Solal A, Hambrecht R, Vanhees L. Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation. Part I: definition of cardiopulmonary exercise testing parameters for appropriate use in chronic heart failure. Eur J Cardiovasc Prev Rehabil. 2006 Apr;13(2):150-64.

Task Force of the Italian Working Group on Cardiac Rehabilitation and Prevention (Gruppo Italiano di Cardiologia Riabilitativa e Prevenzione, GICR); Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology; Piepoli MF, Corrà U, Agostoni PG, Belardinelli R, Cohen-Solal A, Hambrecht R, Vanhees L. Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation Part II: How to perform cardiopulmonary exercise testing in chronic heart failure. Eur J Cardiovasc Prev Rehabil. 2006 Jun;13(3):300-11.

WEIR JB. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol. 1949 Aug;109(1-2):1-9. No abstract available.

Responsible Party:	Gianfranco Parati, Professor, Istituto Auxologico Italiano, Milan, Italy
ClinicalTrials.gov Identifier:	NCT00924833 History of Changes
Other Study ID Numbers:	09F602
Study First Received:	February 19, 2009
Results First Received:	February 19, 2009
Last Updated:	September 1, 2009
Health Authority:	Italy: Ethics Committee

Keywords provided by Istituto Auxologico Italiano:

hypoxia
autonomic nervous system
blood pressure
heart rate

exercise
heart failure
receptors, adrenergic, beta.

Additional relevant MeSH terms:

Heart Failure
Anoxia
Heart Diseases
Cardiovascular Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Carvedilol
Nebivolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic beta-1 Receptor Antagonists

ClinicalTrials.gov processed this record on May 22, 2013