Exercise Training in Heart Failure: Changes in Cardiac Structure and Function

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT02275819
• Collaborator: (none)
• Enrollment: 11
• Location: 1
• Arms: 2
• Actual Duration (Months): 34.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a research study being conducted to better understand the impact of exercise training on changes on the structure and function of the heart. Exercise training in patients with heart failure has been shown to be beneficial at decreasing symptoms of heart failure and improving overall functional capacity or capacity to exercise. However the mechanisms responsible for this are still unclear. This study will look specifically at how exercise creates changes within the hearts filling ability, the hearts pumping strength as well as the hearts ability to rebuild.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Other: Exercise	N/A

Detailed Description

Prevalence of systolic heart failure (HF) is high among the growing population of older adults. Progressive cardiac remodeling and deteriorating cardiac output have been implicated as key factors underlying HF-related exercise intolerance and quality of life. Even after implementing medical and device therapies that moderate remodeling, exercise tolerance remains impaired. While exercise training has been demonstrated to improve exercise capacity, mechanisms facilitating this benefit remain unclear. Peripheral adaptations in the skeletal muscle and vasculature provide at least some benefit, however reverse cardiac remodeling (beyond effects of pharmacological and device therapies) may be additive. The investigators propose to study the impact of 2 different types of exercise on cardiac morphology as well as systolic and diastolic performance and related functional gains. The investigators will compare traditional aerobic training to a novel regimen of inspiratory muscle training (IMT). IMT is a specific type of exercise training that may be particularly useful for frail, infirmed HF patients who are unlikely to tolerate aerobic training. Effects of IMT on remodeling have not been previously studied.

The proposed echocardiography pilot study builds on a funded VA Merit F0834-R "Exercise Therapy to Reduce Heart Failure Symptoms; Sorting Mechanisms of Benefit" (Exercise therapy) PI, Forman that compares different modes of exercise training in older (age 50yrs) systolic (EF 45%) HF patients. The original study assesses peripheral mechanisms affected by exercise training, but was not designed to assess cardiac remodeling. The proposed pilot study provides a vital complementary analysis, i.e., it adds assessments of cardiac remodeling as well as related changes in systolic and diastolic performance.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Non-randomized case control study with two groups. One group received exercise and the controls did not.Non-randomized case control study with two groups. One group received exercise and the controls did not.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Exercise Training in Heart Failure: Structural and Functional Cardiac Remodeling
• Actual Study Start Date: Jun 6, 2016
• Actual Primary Completion Date: Apr 23, 2019
• Actual Study Completion Date: Apr 23, 2019

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: control Will not receive intervention with exercise
Active Comparator: Intervention group 2 groups will receive 2 different types of therapy (exercise or Inspiratory Muscle Therapy)	Other: Exercise; Exercise (walking 3 times a week for 60 minutes) or Inspiratory Muscle Therapy (breathing against an inspiratory resistive load 3 times a week for up to 60 minutes)

Outcome Measures

Primary Outcome Measures

1. Change in Left Ventricular Systolic Function. [Baseline and endpoint at 3-5 months]

   Change in left ventricular ejection fraction.

2. Change in Left Ventricular Structure. [Baseline and endpoint at 3-5 months]

   Change in left ventricular mass.

3. Change in Diastolic Function. [Baseline and endpoint at 3-5 months]

   Change in mitral annular early diastolic velocity (e')

4. Change in Left Ventricular (LV) Diastolic Function [Baseline and endpoint at 3-5 months]

   Change in the ratio of early mitral in-flow velocity (E) to mitral annular early diastolic velocity (e')

5. Change in Right Ventricular Function [Baseline and endpoint at 3-5 months]

   Change in tricuspid annular tissue doppler velocity

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• New York Heart Association (NYHA) class II or III for the previous three months despite a minimum of 6 weeks of optimal treatment.

• Age >50 years.

• Left Ventricular Ejection Fraction (LVEF)<45% (by echocardiogram or radionucleotide imaging study within 6 months of enrollment). If a patient has initiated or received any therapy that might improve the ejection fraction, the qualifying EF must be assessed after the patient is on a stable dose of these therapies. Additionally the LVEF of <45% will be confirmed with a brief echocardiogram prior to randomization. If LVEF is not 45%, the patient will not be enrolled in to the study.

• Optimal therapy according to the American Heart Association (AHA)/American College of Cardiology (ACC) and the Heart Failure Society of America (HFSA) Heart Failure (HF) guidelines, including treatment with an angiotensin-converting-enzyme (ACE) Inhibitor (or an angiotensin receptor blocker) and beta-blocker therapy (for at least 6 weeks), or have documented reason for variation, including medication intolerance, contraindication, patient preference, or personal physician's judgment.

In addition to the above we have now added patients with heart failure with preserved ejection fraction (similar to the parent study )pending Institutional Review Board (IRB) review.

Exclusion Criteria:

• Major cardiovascular event or procedure within the prior 6 weeks.

• Dementia.

• Severe chronic obstructive pulmonary disease (COPD) (FEV1<50%), peripheral vascular disease (PVD), and/or Anemia.

• End-stage malignancy.

• Severe valvular heart disease.

• Orthopedic exercise limitation.

• Women who are pregnant, breastfeeding, or likely to become pregnant within the next 6 months.

• Psychiatric hospitalization within the last 3 months.

• Implantable Cardioverter Defibrillator (ICD) device with heart rate limits that prohibit exercise assessments or exercise training. Referring physicians will be provided with an opportunity to reprogram devices so that patients can participate.

• Chronic ethyl alcohol (ETOH) or drug dependency.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA	Boston	Massachusetts	United States	02130

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

• Principal Investigator: Jayashri Aragam, MD, VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Study Documents (Full-Text)

• Informed Consent Form - Jul 13, 2015
• Study Protocol and Statistical Analysis Plan - Sep 20, 2017

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT02275819
• Other Study ID Numbers: E1423-P
• First Posted: Oct 27, 2014
• Last Update Posted: Mar 8, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by VA Office of Research and Development: Heart Failure; Exercise; Echocardiography
• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Recruitment Details

Recruitment occurred at VA Boston Healthcare System cardiology related clinics from 6/6/2016 to 12/21/2018. As per the protocol the recruitment was supposed to begin in 2014. Unfortunately there were a number of issues including the fact that the parent study moved to Pittsburgh and we were not able to start recruitment till 2016.

Pre-assignment Detail

13 participants were consented but only 11 were enrolled. Two were excluded from randomization due to subsequent echocardiogram or pulmonary function screening not meeting enrollment criteria. One was withdrawn after enrollment due to increasing symptoms of heart failure. Due to the small number of participants enrolled in each of the active intervention arms we combined participants from both intervention groups and analyzed against the controls.

Arm/Group Title	Control	Intervention Group
Arm/Group Description	Will not receive intervention with exercise	2 groups will receive 2 different types of exercise
Period Title: Overall Study
STARTED	5	6
COMPLETED	5	5
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Control	Intervention Group	Total
Arm/Group Description	Will not receive intervention with exercise	2 groups will receive 2 different types of exercise	Total of all reporting groups
Overall Participants	5	5	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 40%	2 40%	4 40%
>=65 years	3 60%	3 60%	6 60%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.6 (8.4)	67.2 (4.4)	68.4 (6.4)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	5 100%	5 100%	10 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 20%	1 20%	2 20%
White	4 80%	4 80%	8 80%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	5 100%	5 100%	10 100%

Outcome Measures

1. Primary Outcome

Title	Change in Left Ventricular Systolic Function.
Description	Change in left ventricular ejection fraction.
Time Frame	Baseline and endpoint at 3-5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intervention Group
Arm/Group Description	Will not receive intervention with exercise	2 groups will receive 2 different types of exercise
Measure Participants	5	5
Mean (Standard Deviation) [percent LVEF]	.82 (3.54)	-1.90 (1.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Intervention Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.14
	Comments
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Change in Left Ventricular Structure.
Description	Change in left ventricular mass.
Time Frame	Baseline and endpoint at 3-5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intervention Group
Arm/Group Description	Will not receive intervention with exercise	2 groups will receive 2 different types of exercise
Measure Participants	5	5
Mean (Standard Deviation) [grams]	-34.8 (49.8)	3.1 (40.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Intervention Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.22
	Comments
	Method	t-test, 2 sided
	Comments

3. Primary Outcome

Title	Change in Diastolic Function.
Description	Change in mitral annular early diastolic velocity (e')
Time Frame	Baseline and endpoint at 3-5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intervention Group
Arm/Group Description	Will not receive intervention with exercise	2 groups will receive 2 different types of exercise
Measure Participants	5	5
Mean (Standard Deviation) [centimeters/second]	.31 (.68)	-1.07 (1.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Intervention Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.12
	Comments
	Method	t-test, 2 sided
	Comments

4. Primary Outcome

Title	Change in Left Ventricular (LV) Diastolic Function
Description	Change in the ratio of early mitral in-flow velocity (E) to mitral annular early diastolic velocity (e')
Time Frame	Baseline and endpoint at 3-5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intervention Group
Arm/Group Description	Will not receive intervention with exercise	2 groups will receive 2 different types of exercise
Measure Participants	5	5
Mean (Standard Deviation) [ratio]	-1.85 (3.06)	2.68 (3.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Intervention Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.08
	Comments
	Method	t-test, 2 sided
	Comments

5. Primary Outcome

Title	Change in Right Ventricular Function
Description	Change in tricuspid annular tissue doppler velocity
Time Frame	Baseline and endpoint at 3-5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intervention Group
Arm/Group Description	Will not receive intervention with exercise	2 groups will receive 2 different types of exercise
Measure Participants	5	5
Mean (Standard Deviation) [centimeters/second]	0.16 (1.04)	-0.70 (2.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Intervention Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Adverse event data was collected while participants were enrolled from enrollment until collection of the final study endpoint at 3-5 months.
Arm/Group Title	Control		Intervention Group
Arm/Group Description	Will not receive intervention with exercise		2 groups will receive 2 different types of exercise
All Cause Mortality
	Control		Intervention Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Serious Adverse Events
	Control		Intervention Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		4/5 (80%)
Cardiac disorders
HF exacerbation	0/5 (0%)	0	1/5 (20%)	1
Low BP	0/5 (0%)	0	1/5 (20%)	1
A-fib Hospitalization	0/5 (0%)	0	1/5 (20%)	1
Respiratory, thoracic and mediastinal disorders
ER Visit	0/5 (0%)	0	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Control		Intervention Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		1/5 (20%)
General disorders
Not Fasted	0/5 (0%)	0	1/5 (20%)	1

Limitations/Caveats

Participation in this study hinged on recruitment into the parent study which was delayed due to various location and staff changes and early termination.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.