Acupuncture on Cardiac and Autonomic Function in Human Heart Failure

• Sponsor: The Cleveland Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01804816
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arms: 2
• Duration (Months): 106
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Acupuncture treatment may improve the cardiac function and the quality of life in heart failure patients. These effects may be related to the inhibition of sympathetic activity and/or increased vagal function. The suppression of inflammatory reaction with acupuncture treatment may also be associated with these outcomes. Specific aims include:

1. To evaluate the effect of acupuncture treatment on human cardiac sympathetic/vagal activity

2. To evaluate the effect of acupuncture treatment on cardiac function and functional capacity

3. To evaluate the general health score of the quality-of-life with acupuncture treatment

4. To explore the mechanism of acupuncture treatment on inflammation and nitrative stress in heart failure patients.

Condition or Disease	Intervention/Treatment	Phase
Chronic Heart Failure	Procedure: Acupuncture; Other: No Intervention	N/A

Detailed Description

The primary aim of this study is to evaluate the effect of acupuncture treatment on cardiac sympathetic/vagal activity in chronic heart failure patients. The investigators would like to investigate the effect of acupuncture treatment on cardiac function and the general health score of the quality-of-life. The investigators would like to further explore the mechanism of acupuncture treatment on autonomic imbalance and chronic inflammatory reaction in heart failure patients by comparing the treatment and sham groups, the baseline before the treatment and the changes after treatment.

Chronic heart failure affects millions people and is a leading cause of death in US. Despite of advance in diagnoses and treatments, the long-term prognosis and quality of life of chronic heart failure patients remain poor. The mortality of chronic heart failure is estimated 50% within 4 years, and is more than 50% in patients with severe chronic heart failure.

Chronic heart failure results from the left ventricular (LV) systolic and/or diastolic dysfunction. Autonomic imbalance with sustained sympathetic overdrive and vagal withdrawal plays an important role in the development of chronic heart failure. This autonomic dysregulation is related to increased heart rate, excess inflammatory response, progressive LV dysfunction, increased mortality and morbidity in chronic heart failure patients. Sympathetic active inhibition with beta-adrenergic receptor blockers has shown significant reduction in mortality and morbidity in chronic heart failure patients. Also modulation of parasympathetic activation with electrical vagus nerve stimulation (VNS) has demonstrated as a potential therapy for chronic heart failure.

Acupuncture has been widely used in China for thousands of years to treat a variety of diseases and their symptoms. Except pain disorders, increasing evidences have shown that acupuncture may be useful for cardiovascular diseases, such as coronary artery disease, hypertension and chronic heart failure. It has been demonstrated that certain acupuncture points have shown to inhibit cardiac sympathetic activation or increase cardiac vagal component in both experimental animals and clinical studies. Recently a small clinical trial by Dr. Kristen, et al has found that acupuncture could improve exercise tolerance in chronic heart failure patients.

The investigators hypothesize that acupuncture treatment may improve the cardiac function and the quality of life in heart failure patients. These effects may be related to the inhibition of sympathetic activity and/or increased vagal function. The suppression of inflammatory reaction with acupuncture treatment may also be associated with these outcomes. In addition to optimized standard heart failure medications, acupuncture may be a safe therapeutic strategy in chronic heart failure treatment. Studies of acupuncture on cardiac autonomic activity in heart failure may show more evidence of acupuncture treatment in chronic heart failure patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Acupuncture on Cardiac and Autonomic Function in Human Heart Failure
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Acupuncture 10 standardized verum acupuncture (VA) sessions twice a week, over 5 weeks. The 5 weeks of acupuncture were scheduled after the period of no acupuncture for each subject.	Procedure: Acupuncture; Standardized acupuncture administration for 10 sessions.
Placebo Comparator: No Acupuncture No acupuncture treatment or other study intervention over 5 weeks. All subjects had a 5 week period of "no acupuncture" prior to the 5 weeks of acupuncture sessions.	Other: No Intervention; No intervention during this period. This was a control period. Each subject acted as their own control.

Outcome Measures

Primary Outcome Measures

1. Change in Cardiac Function: LVEF [Baseline, Week 7, Week 13]

   Left ventricular ejection fraction (LVEF) percentage was measured at baseline, after 5 weeks of no treatment and just prior to acupuncture treatment, and after 5 weeks of acupuncture treatments.

2. Change in 6-Minute Walk Distance [Baseline, Week 7, Week 13]

Secondary Outcome Measures

1. Change in Quality of Life (QOL) [Baseline, Week 7, Week 13]

   Patients quality of life (QOL) was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline, after 5 weeks of no treatment and just prior to acupuncture treatment, and after 5 weeks of acupuncture treatments. Scores reported here are the Quality of Life Scores, which range from 0 to 100. Higher numbers indicate a better quality of life.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥ 21 years

• Congestive Heart Failure (CHF), New York Heart Association (NYHA) class II-III, LVEF ≤40%

• All patients will have sinus rhythm and compensate with individually optimized standard heart failure medications. Routine medications will be continued during the study period

• Able and willing to give informed consent or comply with study procedures.

Exclusion Criteria:

• Acupuncture treatment within 3 months before the beginning of the study

• Presents with cutaneous eczema at potential acupoints

• Have a history of major bleeding or increased propensity of excessive bleeding due to platelet dysfunction

• Currently taking anti-coagulants (e.g. warfarin)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• The Cleveland Clinic

Investigators

• Principal Investigator: W.H. Wilson Tang, MD, The Cleveland Clinic
• Principal Investigator: Yanming Huang, MD PhD, The Cleveland Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

• Deng YJ, Liang WX, Cheng SY. [Influence of acupoint-catgut-implantation on blood pressure and cardiac function in chronic congestive heart failure rats]. Zhen Ci Yan Jiu. 2011 Feb;36(1):40-5. Chinese.
• Kristen AV, Schuhmacher B, Strych K, Lossnitzer D, Friederich HC, Hilbel T, Haass M, Katus HA, Schneider A, Streitberger KM, Backs J. Acupuncture improves exercise tolerance of patients with heart failure: a placebo-controlled pilot study. Heart. 2010 Sep;96(17):1396-400. doi: 10.1136/hrt.2009.187930. Epub 2010 Jun 15.
• Kurono Y, Minagawa M, Ishigami T, Yamada A, Kakamu T, Hayano J. Acupuncture to Danzhong but not to Zhongting increases the cardiac vagal component of heart rate variability. Auton Neurosci. 2011 Apr 26;161(1-2):116-20. doi: 10.1016/j.autneu.2010.12.003. Epub 2011 Jan 7.
• Middlekauff HR, Hui K, Yu JL, Hamilton MA, Fonarow GC, Moriguchi J, Maclellan WR, Hage A. Acupuncture inhibits sympathetic activation during mental stress in advanced heart failure patients. J Card Fail. 2002 Dec;8(6):399-406.

• Responsible Party: Wilson Tang, Staff Cellular and Molecular Medicine and Cardiovascular Medicine, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT01804816
• Other Study ID Numbers: 12-580
• First Posted: Mar 5, 2013
• Last Update Posted: Jan 5, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Wilson Tang, Staff Cellular and Molecular Medicine and Cardiovascular Medicine, The Cleveland Clinic: Chronic Heart Failure; Heart Failure
• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Recruitment Details	Participants were recruited from the Cleveland Clinic Heart and Vascular Institute section of Heart Failure and Transplant Medicine.
Pre-assignment Detail	All subjects acted as their own controls for this study and were assigned to a 5 week period of no acupuncture or other study interventions (control) followed by a 5 week period of weekly standardized verum acupuncture (intervention).

Arm/Group Title	No Acupuncture / Acupuncture
Arm/Group Description	5 weeks of no treatment followed by 5 weeks of standardized verum acupuncture.
Period Title: No Acupuncture (Initial 5 Weeks)
STARTED	14
COMPLETED	11
NOT COMPLETED	3
Period Title: No Acupuncture (Initial 5 Weeks)
STARTED	11
COMPLETED	10
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	No Acupuncture/Acupuncture
Arm/Group Description	No Acupuncture: No treatment. Baseline period. Acupuncture: Standardized acupuncture administration for 10 sessions using acupuncture needles.
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 70%
>=65 years	3 30%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.9 (9.8)
Sex: Female, Male (Count of Participants)
Female	5 50%
Male	5 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	10 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 40%
White	6 60%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Change in Cardiac Function: LVEF
Description	Left ventricular ejection fraction (LVEF) percentage was measured at baseline, after 5 weeks of no treatment and just prior to acupuncture treatment, and after 5 weeks of acupuncture treatments.
Time Frame	Baseline, Week 7, Week 13

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline	Pre-Acupuncture	Post-Acupuncture
Arm/Group Description	Measurements at baseline visit.	Measurements were taken after 5 full weeks of no treatment. This visit occurred 6-7 weeks after the baseline measurements.	Measurements were taken after 10 sessions of standardized verum acupuncture administration using 0.18-0.25×30-60-mm stainless steel needles. Acupuncture sessions were scheduled twice a week for 5 weeks. This post-acupuncture visit occurred within 1 week of finishing the acupuncture sessions.
Measure Participants	10	10	10
Mean (Standard Deviation) [LVEF Percentage]	36.14 (7.23)	36.11 (8.97)	40.59 (9.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baseline, Post-Acupuncture
	Comments
	Type of Statistical Test	Equivalence
	Comments	a=0.05
Statistical Test of Hypothesis	p-Value	0.063
	Comments
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Change in 6-Minute Walk Distance
Time Frame	Baseline, Week 7, Week 13

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline	Pre-Acupuncture	Post-Acupuncture
Arm/Group Description	Measurements at baseline visit	Measurements were taken after 5 full weeks of no treatment. This visit occurred 6-7 weeks after the baseline measurements.	Measurements were taken after 10 sessions of standardized verum acupuncture administration using 0.18-0.25×30-60-mm stainless steel needles. Acupuncture sessions were scheduled twice a week for 5 weeks. This post-acupuncture visit occurred within 1 week of finishing the acupuncture sessions.
Measure Participants	10	10	10
Mean (Standard Deviation) [Feet]	1376.2 (250.19)	1488.0 (264.82)	1515.10 (268.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baseline, Pre-Acupuncture
	Comments	Based on results from prior small clinical trials we estimate the need for 20 patients enrolled to reach 80% statistical power.
	Type of Statistical Test	Equivalence
	Comments	a = 0.05
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Baseline, Post-Acupuncture
	Comments
	Type of Statistical Test	Equivalence
	Comments	a=0.05
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pre-Acupuncture, Post-Acupuncture
	Comments
	Type of Statistical Test	Equivalence
	Comments	a=0.05
Statistical Test of Hypothesis	p-Value	0.441
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Change in Quality of Life (QOL)
Description	Patients quality of life (QOL) was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline, after 5 weeks of no treatment and just prior to acupuncture treatment, and after 5 weeks of acupuncture treatments. Scores reported here are the Quality of Life Scores, which range from 0 to 100. Higher numbers indicate a better quality of life.
Time Frame	Baseline, Week 7, Week 13

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline	Pre-Acupuncture	Post-Acupuncture
Arm/Group Description	Measurements at baseline visit	Measurements were taken after 5 full weeks of no treatment. This visit occurred 6-7 weeks after the baseline measurements.	Measurements were taken after 10 sessions of standardized verum acupuncture administration using 0.18-0.25×30-60-mm stainless steel needles. Acupuncture sessions were scheduled twice a week for 5 weeks. This post-acupuncture visit occurred within 1 week of finishing the acupuncture sessions.
Measure Participants	10	10	10
Mean (Standard Deviation) [score on a scale]	65.00 (26.59)	67.50 (24.36)	69.17 (25.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baseline, Post-Acupuncture
	Comments
	Type of Statistical Test	Equivalence
	Comments	a=0.05
Statistical Test of Hypothesis	p-Value	0.729
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	10 weeks
Arm/Group Title	No Acupuncture/Acupuncture
Arm/Group Description	No Acupuncture: No treatment. Baseline period. Acupuncture: Standardized acupuncture administration for 10 sessions using acupuncture needles.
All Cause Mortality
	No Acupuncture/Acupuncture
	Affected / at Risk (%)	# Events
Total	0/14 (0%)
Serious Adverse Events
	No Acupuncture/Acupuncture
	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)
Cardiac disorders
Hospitalization	2/14 (14.3%)	2
Other (Not Including Serious) Adverse Events
	No Acupuncture/Acupuncture
	Affected / at Risk (%)	# Events
Total	0/14 (0%)

Limitations/Caveats

These results should be interpreted with caution. With only 10 subjects, the study may be under-powered to detect a significant difference.

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.