Effects of Cardiac Rehabilitation on High Mobility Group Box-1 Levels After Acute Myocardial Infarction - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single Blind (Investigator); Primary Purpose: Basic Science
Condition:	Acute Myocardial Infarction
Intervention:	Other: Exercise-based Cardiac Rehabilitation program

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was a single-center, randomized, controlled study carried out from October 2008 to January 2009 at the Department of Clinical Medicine, Cardiovascular and Immunological Sciences, University of Naples “Federico II”.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Exercise Training Group	Postinfarction patients undergoing 6-month exercise-based Cardiac Rehabilitation Program
Control Group	Postinfarction patients NOT enrolled in exercise-based Cardiac Rehabilitation program.

Participant Flow: Overall Study

	Exercise Training Group	Control Group
STARTED	37	38
COMPLETED	37	38
NOT COMPLETED	0	0

Baseline Characteristics

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Reporting Groups

	Description
Exercise Training Group	Postinfarction patients undergoing 6-month exercise-based Cardiac Rehabilitation Program
Control Group	Postinfarction patients NOT enrolled in exercise-based Cardiac Rehabilitation program.
Total	Total of all reporting groups

Baseline Measures

	Exercise Training Group	Control Group	Total
Number of Participants [units: participants]	37	38	75
Age [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	28	29	57
>=65 years	9	9	18
Age [units: years] Mean ± Standard Deviation	60.8 ± 7.0	59.5 ± 7.7	60.4 ± 7.5
Gender [units: participants]
Female	9	6	15
Male	28	32	60
Region of Enrollment [units: participants]
Italy	37	38	75

Outcome Measures

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1. Primary:

High Mobility Group Box-1 (HMGB1)Levels at Baseline and 6 Months [ Time Frame: baseline and 6-month follow-up ]

Measure Type	Primary
Measure Title	High Mobility Group Box-1 (HMGB1)Levels at Baseline and 6 Months
Measure Description	High mobility group box-1 (HMGB1) is a ubiquitous nuclear protein, constitutively expressed in quiescent cells, where it is involved in several cellular functions, including determination of nucleosomal structure and stability, and binding of transcription factors to DNA sequences. HMGB1 has been recently recognized as a critical mediator of inflammatory processes: the passive release of this protein from necrotic or damaged cells represents an effective stimulus triggering the inflammatory response.
Time Frame	baseline and 6-month follow-up
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Exercise Training Group	Postinfarction patients undergoing 6-month exercise-based Cardiac Rehabilitation Program
Control Group	Postinfarction patients NOT enrolled in exercise-based Cardiac Rehabilitation program.

Measured Values

	Exercise Training Group	Control Group
Number of Participants Analyzed [units: participants]	37	38
High Mobility Group Box-1 (HMGB1)Levels at Baseline and 6 Months [units: ng/ml] Mean ± Standard Deviation
Baseline	27.6 ± 27.8	24.5 ± 18.6
6 months	11.7 ± 7.0	20.5 ± 15.6

Statistical Analysis 1 for High Mobility Group Box-1 (HMGB1)Levels at Baseline and 6 Months

Groups ^[1]	All groups
Method ^[2]	t-test, 2 sided
P Value ^[3]	<0.05

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Sample size determination was based on a t-test assuming a normal distribution with non-equal variance with the mean and standard deviation for the experimental group (postinfarction patients) of HMGB1 levels equal to 15 ± 7 and 2 ± 1 ng/dl for the control group derived from a previous study, respectively. The required sample size was calculated to be 30 subjects per group to detect on the size of one SD with α value of 0.05 (two-sided) and power (1 – β) of 0.8.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

2. Secondary:

Peak Oxygen Consumption (VO2peak) at Baseline and 6 Months [ Time Frame: Baseline and 6-month follow-up ]

Measure Type	Secondary
Measure Title	Peak Oxygen Consumption (VO2peak) at Baseline and 6 Months
Measure Description	Oxygen consumption at peak exercise stress testing (VO2peak) was obtained breath-by-breath with use of a computerized metabolic cart. VO2peak was recorded as the mean value of VO2 during the last 20 s of the test and expressed in millilitres per kilogram per minute.
Time Frame	Baseline and 6-month follow-up
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
intention to treat (ITT) analysis

Reporting Groups

	Description
Exercise Training Group	Postinfarction patients undergoing 6-month exercise-based Cardiac Rehabilitation Program
Control Group	Postinfarction patients NOT enrolled in exercise-based Cardiac Rehabilitation program.

Measured Values

	Exercise Training Group	Control Group
Number of Participants Analyzed [units: participants]	37	38
Peak Oxygen Consumption (VO2peak) at Baseline and 6 Months [units: ml/kg/min] Mean ± Standard Deviation
baseline	16.4 ± 1.5	16.7 ± 2.2
6 months	21.0 ± 2.4	16.3 ± 1.8

Statistical Analysis 1 for Peak Oxygen Consumption (VO2peak) at Baseline and 6 Months

Groups ^[1]	All groups
Method ^[2]	t-test, 2 sided
P Value ^[3]	<0.05

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

3. Other Pre-specified:

Heart Rate Recovery at Baseline and 6 Months [ Time Frame: baseline and 6 month follow-up ]

Measure Type	Other Pre-specified
Measure Title	Heart Rate Recovery at Baseline and 6 Months
Measure Description	The autonomic nervous system (ANS) is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. It is subdivided into two subsystems: the parasympathetic (vagal) and sympathetic nervous system. Sympatho-vagal imbalance is evaluated by post-exercise Heart Rate Recovery (HRR), defined as the fall in heart rate during the first minute after exercise (beats/min). HRR is a marker of vagal tone which is a powerful predictor of all-cause mortality in patients with coronary artery disease.
Time Frame	baseline and 6 month follow-up
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Exercise Training Group	Postinfarction patients undergoing 6-month exercise-based Cardiac Rehabilitation Program
Control Group	Postinfarction patients NOT enrolled in exercise-based Cardiac Rehabilitation program.

Measured Values

	Exercise Training Group	Control Group
Number of Participants Analyzed [units: participants]	37	38
Heart Rate Recovery at Baseline and 6 Months [units: beats/min] Mean ± Standard Deviation
baseline	13.4 ± 1.7	13.8 ± 2.7
6 months	19.7 ± 3.4	12.4 ± 2.5

Statistical Analysis 1 for Heart Rate Recovery at Baseline and 6 Months

Groups ^[1]	All groups
Method ^[2]	t-test, 2 sided
P Value ^[3]	<0.05

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

All Principal Investigators ARE employed by the organization sponsoring the study.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Prof. Carlo Vigorito, Director Cardiac Rehabilitation Unit, Federico II University
Organization: University of Naples Federico II
phone: +39081746 ext 2639
e-mail: vigorito@unina.it

Publications:

Giallauria F, Cirillo P, Lucci R, Pacileo M, De Lorenzo A, D'Agostino M, Moschella S, Psaroudaki M, Del Forno D, Orio F, Vitale DF, Chiariello M, Vigorito C. Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide. Eur J Cardiovasc Prev Rehabil. 2008 Feb;15(1):113-8.

Giallauria F, Galizia G, Lucci R, D'Agostino M, Vitelli A, Maresca L, Orio F, Vigorito C. Favourable effects of exercise-based Cardiac Rehabilitation after acute myocardial infarction on left atrial remodeling. Int J Cardiol. 2008 Aug 2; [Epub ahead of print]

Giallauria F, De Lorenzo A, Pilerci F, Manakos A, Lucci R, Psaroudaki M, D'Agostino M, Del Forno D, Vigorito C. Reduction of N terminal-pro-brain (B-type) natriuretic peptide levels with exercise-based cardiac rehabilitation in patients with left ventricular dysfunction after myocardial infarction. Eur J Cardiovasc Prev Rehabil. 2006 Aug;13(4):625-32.

Giallauria F, De Lorenzo A, Pilerci F, Manakos A, Lucci R, Psaroudaki M, D'Agostino M, Del Forno D, Vigorito C. Long-term effects of cardiac rehabilitation on end-exercise heart rate recovery after myocardial infarction. Eur J Cardiovasc Prev Rehabil. 2006 Aug;13(4):544-50.

Giallauria F, Lucci R, Pietrosante M, Gargiulo G, De Lorenzo A, D'Agostino M, Gerundo G, Abete P, Rengo F, Vigorito C. Exercise-based cardiac rehabilitation improves heart rate recovery in elderly patients after acute myocardial infarction. J Gerontol A Biol Sci Med Sci. 2006 Jul;61(7):713-7.

Cirillo P, Golino P, Calabrò P, Calì G, Ragni M, De Rosa S, Cimmino G, Pacileo M, De Palma R, Forte L, Gargiulo A, Corigliano FG, Angri V, Spagnuolo R, Nitsch L, Chiariello M. C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation. Cardiovasc Res. 2005 Oct 1;68(1):47-55.

Cirillo P, Calì G, Golino P, Calabrò P, Forte L, De Rosa S, Pacileo M, Ragni M, Scopacasa F, Nitsch L, Chiariello M. Tissue factor binding of activated factor VII triggers smooth muscle cell proliferation via extracellular signal-regulated kinase activation. Circulation. 2004 Jun 15;109(23):2911-6. Epub 2004 Jun 1.

Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002 Mar 5;105(9):1135-43. Review.

Yamada S, Maruyama I. HMGB1, a novel inflammatory cytokine. Clin Chim Acta. 2007 Jan;375(1-2):36-42. Epub 2006 Jul 25. Review.

Giallauria F, Cirillo P, Lucci R, Pacileo M, D'Agostino M, Maietta P, Vitelli A, Chiariello M, Vigorito C. Autonomic dysfunction is associated with high mobility group box-1 levels in patients after acute myocardial infarction. Atherosclerosis. 2009 Jul 14; [Epub ahead of print]

Giallauria F, Cirillo P, Lucci R, Pacileo M, D'agostino M, Maietta P, Vitelli A, Chiariello M, Vigorito C. Effects of exercise-based cardiac rehabilitation on high mobility group box-1 levels after acute myocardial infarction: rationale and design. J Cardiovasc Med (Hagerstown). 2009 Aug;10(8):659-63.

Publications automatically indexed to this study:

Giallauria F, Cirillo P, D'agostino M, Petrillo G, Vitelli A, Pacileo M, Angri V, Chiariello M, Vigorito C. Effects of exercise training on high-mobility group box-1 levels after acute myocardial infarction. J Card Fail. 2011 Feb;17(2):108-14. Epub 2010 Oct 29.

Responsible Party:	Carlo Vigorito, Department of Clinical Medicine, Cardiovascular and Immunological Sciences
ClinicalTrials.gov Identifier:	NCT00755131 History of Changes
Other Study ID Numbers:	UNINA-15775
Study First Received:	September 17, 2008
Results First Received:	November 5, 2009
Last Updated:	January 25, 2010
Health Authority:	Italy: National Institute of Health