Effects of Nebivolol Versus Carvedilol on Cardiopulmonary Function at High Altitude in Healthy Subjects.

NCT00924833 | Completed Phase 4 Results DMC

• 1 other identifier: 09F602
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypoxia; Altitude; Heart Failure

Keywords

hypoxia; autonomic nervous system; blood pressure; heart rate; exercise; heart failure; receptors, adrenergic, beta.

Outcome Measures

Primary Outcomes (4)

• Peak Exercise Oxygen Consumption

  Oxygen consumption at peak of exercise

  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.

• Delta Peak Exercise Oxygen Consumption Time 1 Versus Time 3

  Difference in peak exercise oxygen consumption between Time 1 and Time 3 (Time 3 - Time 1)

  Time 1: sea level, baseline, no treatment. Time 3: within the first two days of high altitude exposure, under treatment.

• Peak Exercise Minute Ventilation

  Minute ventilation at peak of exercise. Minute ventilation = tidal volume (ml) multiplied by the respiratory rate (breaths/min)

  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.

• Delta Peak Exercise Minute Ventilation Time 1 Versus Time 3.

  Difference in peak exercise minute ventilation between Time 1 and Time 3 (Time 3 - Time 1. Minute ventilation = tidal volume (ml) multiplied by the respiratory rate (breaths/min).

  Time 1: sea level, baseline, no treatment. Time 3: within the first two days of high altitude exposure, under treatment.

Secondary Outcomes (5)

• Peak Exercise Oxygen Saturation

  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.

• Systolic Pulmonary Artery Pressure.

  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.

• Resting Energy Expenditure

  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.

• Sitting Blood Pressure and Heart Rate

  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.

• Mean 24 Hour/Daytime/Night-time Blood Pressure and Heart Rate

  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.

Study Arms (3)

placebo

PLACEBO COMPARATOR

Placebo tablets. One tablet twice daily.

Drug: placebo

2: Carvedilol

ACTIVE COMPARATOR

Carvedilol 25 mg tablets. One tablet twice daily.

Drug: Carvedilol

3: Nebivolol

ACTIVE COMPARATOR

Nebivolol 5 mg tablets. One nebivolo tablet daily. One placebo tablet daily.

Drug: Nebivolol

Interventions

placebo DRUG

placebo tablet BID

placebo

Carvedilol DRUG

Carvedilol 25 mg tablets. One tablet twice daily.

2: Carvedilol

Nebivolol DRUG

nebivolol 5 mg tablets. One nebivolol tablet daily. One placebo tablet daily.

3: Nebivolol

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Istituto Auxologico Italiano: lead
• Menarini Group: collaborator

Study Sites (1)

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

Milan, 20148, Italy

Location

Related Publications (8)

• 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. doi: 10.1161/CIRCULATIONAHA.105.605527. Epub 2006 Sep 18.

  PMID: 16982943 BACKGROUND

• 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. doi: 10.1016/j.ejheart.2006.02.001. Epub 2006 Mar 13.

  PMID: 16533619 BACKGROUND

• 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. doi: 10.1097/HJH.0b013e3281fc975a. No abstract available.

  PMID: 17563527 BACKGROUND

• 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. doi: 10.1097/01.hjh.0000163132.84890.c4. No abstract available.

  PMID: 15775768 BACKGROUND

• 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. doi: 10.1016/j.euje.2005.12.014. Epub 2006 Feb 2.

  PMID: 16458610 BACKGROUND

• 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, Corra 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. doi: 10.1097/01.hjr.0000209812.05573.04.

  PMID: 16575267 BACKGROUND

• 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, Corra 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. doi: 10.1097/00149831-200606000-00003.

  PMID: 16926657 BACKGROUND

• WEIR JB. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol. 1949 Aug;109(1-2):1-9. doi: 10.1113/jphysiol.1949.sp004363. No abstract available.

  PMID: 15394301 BACKGROUND

MeSH Terms

Conditions

Hypoxia; Heart Failure; Motor Activity

Interventions

Carvedilol; Nebivolol

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases; Behavior

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring; Ethanolamines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

We used standard doses of both beta blockers and observed similar HR reductions. We could not individually titrate drug doses. The degree of beta blockade might have been different in each subject.

Results Point of Contact

• Title: Gianfranco Parati, Professor
• Organization: Istituto Auxologico Italiano

gianfranco.parati@unimib.it

+3961911

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 19, 2009
• First Posted: June 19, 2009
• Study Start: May 1, 2006
• Primary Completion: November 1, 2006
• Study Completion: November 1, 2006
• Last Updated: September 2, 2009
• Results First Posted: June 19, 2009

Record last verified: 2009-02

Locations

IT (1)