Feasibility Testing of a Randomized Controlled Trial of Acupuncture to Improve Symptoms for Individuals With Stable Angina (AIMS-A)
Phase: NA
Conditions: Angina, Stable, Chest Pain, Microvascular Angina, Heart Failure
Sponsor: University of Illinois at Chicago

 
 
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Research Protocol 
 
Project Title: Feasibility Testing of a Randomized Controlled Trial of Acupuncture to Improve Symptoms 
for Individuals with Stable Angina (AIMS-A) 
                                                       
a. SIGNIFICANCE 
The significance of managing the symptoms of stable angina cannot be overstated given that; 1) heart disease 
remains the number one killer of individuals in the US, 2) the incidence of stable angina is projected to rise with 
concomitant increases in comorbid conditions, 3) the direct and indirect costs of angina are high, and 4) the 
largest generation of Americans, the “Baby Boomers”, are reaching retirement. A reduction in the amount and 
severity of pain and associated symptoms has the potential to contribute to improvements in functional status 
and quality of life. Camm et al.1 found that one-third of patients with stable angina have suboptimal 
management of their disease and concluded that neither clinicians nor patients should accept the idea that 
symptoms are unavoidable. 
 
b. INNOVATION  
This study is innovative in that it will: 1) use a theoretically-based TCM model to test the effect of acupuncture 
on angina symptoms; 2) test a complementary therapy for individuals with inadequate pain and symptom 
control; 3) target a population of public health interest, individuals with stable angina whose symptoms are not 
well controlled with conventional therapy; and 4) the use of McGill Pain Questionnaire2 which will allow us to 
better characterize the sensory elements of angina pain location and distribution including intensity, quality, 
and pattern. This therapy has not been tested in a sample of Americans with angina, thus there is a significant 
gap in knowledge of feasibility and efficacy in this population. If found to be effective in a larger trial, the 
addition of acupuncture therapy has the potential to change the western medicine paradigm of treatment of 
angina based solely on a model of obstructive coronary artery disease to a complementary therapy approach 
based on an integrative western medicine/TCM model.  
 
c. APPROACH 
c.1. Introduction 
Currently 15.5 million Americans have ischemic heart disease (IHD).3 Ischemic heart disease puts an 
enormous strain on the health care system, the work-force, caregivers, and afflicted individuals.4 Ischemic 
heart disease has a chronic, stable form (angina) signifying partial obstruction of flow5 or microvascular 
dysfunction6 and comes with substantial lifetime consequences including heart failure7, atrial fibrillation8, 
reinfarction9, and cardiac arrest.9 Direct and indirect costs of IHD for 2011 were estimated to be $215.6 
billion10,11. Stable angina is associated with multiple symptoms12, impaired functional status13,14, and reduced 
quality of life (QoL).5,15  Stable angina is a syndrome induced by transient myocardial ischemia resulting in 
chest pain and associated symptoms such as shortness of breath and fatigue16. Ischemia may be due to 
obstructed coronary arteries or microvascular coronary dysfunction (MCD)17.  
 
Sex differences in the clinical presentation of IHD have been reported18. Heart disease in men is more often 
due to occlusions in their main coronary arteries, referred to as obstructive coronary artery 
disease19,20. Humphries et al. found that 7.1% of males vs. 23.3% of females in a large (n=32,856) cohort of 
Canadians undergoing elective angiography for suspected IHD18 had angiographically normal coronary 
arteries. A diagnosis of normal coronary arteries has been reported to be as high as five times more common 
in women6. Women with “normal” coronary arteries are frequently thought to have MCD. To date there has 
been no clear explication of the pathogenesis of microvascular disease21 but it is thought to involve damage to 
the tiny blood vessels in the heart, causing them to narrow, tighten or constrict (spasm). These abnormalities 
may be caused by vasomotor or metabolic regulators6. This reduces blood flow to the myocardium often 
causing symptoms associated with ischemia22. Microvascular coronary dysfunction is more likely to occur in 
younger women. Women with angiographic evidence of stable angina have poorer outcomes compared to 
men17. In one study, hospital readmissions for angina accounted for 45% of adverse outcomes following 
ACS17. Those with stable angina are also at risk for ACS, sudden cardiac death12, and heart failure5,15. 
Therefore, the examination of sex differences in the efficacy of acupuncture for stable angina is critically 
needed. 

 
 
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Guideline-directed therapy for the treatment of stable angina include nitrates, beta-blockers, calcium channel 
blockers, and angiotension converting enzyme (ACE) inhibitors16. These drugs can have side effects such as 
headache, flushing, fatigue, and cough which can lead to non-adherence and lack of symptom control. 
Acupuncture has been recommended as a potential complementary or alternative treatment for hypertension23, 
hyperlipidemia24, and smoking cessation25 but has not been proposed for the treatment of stable angina in the 
US16. The National Institutes of Health (NIH) has recommended acupuncture as an alternative or 
complementary therapy for a number of conditions26. 
 
c.2. Importance of the Problem 
The number one cause of death for individuals in the United States is IHD3. As noted, IHD is associated with 
poor outcomes including heart failure7, atrial fibrillation8, reinfarction9, and cardiac arrest 9 and women have 
poorer outcomes compared to men with IHD27. We have demonstrated in our prior studies that angina 
symptoms are not as well controlled for women as for men28. We have quantified the burden of symptoms and 
found that women experience a higher number of symptoms and more distress from symptoms despite 
receiving standard care following an episode of ACS29. Our short term goal is to determine, in a rigorously 
controlled trial, if acupuncture is an effective complementary treatment for stable angina. The continued growth 
in the number of older adults and the preponderance of elder females in the population further warrants 
research into symptom management. Symptoms that are well-controlled result in better functional status30 and 
QoL31. Managing heart disease in women is a vital health issue if aging women are to maintain a high QoL. 
 
c.2.1 Side Effects of Anti-anginal Medications and Lack of Symptom Control for Indivduals with Angina 
Standard guideline-directed therapy for the treatment of stable angina relies on pharmacologic therapies 
including anti-platelet agents32,33, statins34, and anti-ischemic agents35. Xu et al. found patients undergoing 
acupuncture complained of side effects from anti-anginal drugs including nitroglycerin related headaches; 
isosorbide related dizziness and nausea/vomiting; and propranolol related chest pain and depression36. 
 
c.2.2. Physiologic Mechanisms of Acupuncture and their Effect on the Cardiovascular System 
Acupuncture regulates the autonomic nervous system and reduces sympathetic stimulation to the heart and 
vasculature by modulating the midbrain, releasing endorphins and dynorphins, with a resultant decrease in 
production of norepinephrine and epinephrine. These processes impact the CV system by reducing blood 
pressure, heart rate, and centrally mediated arrhythmias37. Acupuncture helps relieve pain by: 1) deactivating 
the limbic-paralimbic-neocorticol network system38; 2) activating mu opioid receptors39; 3) increasing serum β 
endorphins40; 4) increasing ACTH release from the anterior pituitary41; and 5) downregulating M1 
macrophages, Interleukin-1β, Interleukin-6, Interleukin-18 and Tumor Necrosis Factor (TNF)42.  
 
 
c.2.3. Theory of Traditional Chinese Medicine  
 
TCM is based on the theory of Yin and Yang: 1) yin and yang are relative opposites to one another (e.g., 
hot/cold, night/day) but are perpetually undergoing transformation (night becomes dawn, dawn becomes day 
etc.); 2) yin and yang are interdependent and nothing can be all yin or all yang; and 3) an imbalance of either 
yin or yang eventually weakens both. When yin and yang are in balance health is sustained43. Disease and/or 
pain ensues when yin and yang are out of balance. When yang (warming) is weak, yin predominates and the 
body is cold, the hands and feet are cold, the skin is pale, and the person is lethargic. Qi is the vital energy 
flowing within and surrounding the body. Qi can be yin or yang44. Disorders of qi or blood can result in pain; 
they can be deficient, or result in excess (stagnant or obstructed). The channels through which qi and blood 
flow in the body are called meridians45. Acupuncture needles are inserted into acupuncture points which 
access the meridians and promote the circulation of qi and blood43. Deficient qi and/or blood is strengthened 
(tonified); excess qi and/or blood is moved to reduce stagnation or obstruction46,47. Thus the yin and yang of 
the body become balanced and pain and other symptoms are reduced43,46. In the TCM model, it is theorized 
that the pain, shortness of breath, and fatigue of stable angina results when there is an excess (stagnant or 
obstructed) or a deficiency in qi and/or blood in the meridians that flow through and around the heart47.  
 
c.2.4. Acupuncture for the Treatment of Angina  
A recent systematic review of 25 RCTs48 and a meta-analysis of 8 RCTs49 of acupuncture for the treatment of 
stable angina in China showed improvements in relief of angina symptoms for the acupuncture treated 

 
 
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participants compared to controls. However there was no reduction in ischemia as measured by ECG or 
reduction in nitroglycerin use. All but two studies (Scandinavian) were performed in China.50,51 The authors 
noted limitations to the studies including heterogeneous samples, lack of adjustment for potential confounders, 
lack of standardization of acupuncture point prescriptions, varying medication prescriptions, and different 
outcome measures. Only one study, conducted in Sweden, addressed duration of acupuncture effect51. This 
study used a randomized crossover design and included 21 individuals (2 women) with angina. Patients in the 
acupuncture group reported a mean reduction in angina episodes from 10.6 to 6.1/week during the 4 weeks of 
therapy and 2 weeks of washout. Duration of effect beyond 2 weeks remains unknown. We will test this in our 
R21 study. Based on available, low quality evidence, an AHA writing group concluded that acupuncture has 
not been studied sufficiently to warrant recommendation as a treatment option for relief of angina symptoms for 
patients with stable IHD52. 
 
c.2.5. Acupuncture Use in the United States 
Acupuncture use is on the rise in the United States. In 2012, Americans 
received 3,484,000 acupuncture sessions which was a significant increase 
from the years 2002 to 200753. Overall 34% of American adults in 2012 
used some form of complimentary alternative medicine (CAM)53. In 2007 a 
total of $33.9 billion dollars was spent on CAM54,55. Most Americans use 
CAM to supplement western medical treatments as opposed to replace 
them56-58 and/or treat symptoms of chronic disease or side effects from 
medications54,59,60.  Almost 8% of those using CAM did not tell their 
physicians61. Since women with symptoms of stable angina are seeking 
acupuncture and other CAM therapies for amelioration of symptoms, it is 
imperative to begin to evaluate the feasibility of using acupuncture to treat 
the pain and symptoms of stable angina. In addition, determination of sex 
differences in response to acupuncture is important. 
 
c.2.6. Lack of a Standardized Acupuncture Protocol for Stable 
Angina. 
There has been no attempt to standardize a set of acupuncture points used to treat chest pain or stable 
angina. Clinical practice guidelines cannot be developed until standardized study protocols are devised which 
offer investigators an algorithm for implementing consistent repeatable acupuncture interventions that can be 
tested in future trials. To overcome this gap, co-PI Schlaeger  has developed an acupuncture point prescription 
(a set of standardized acupuncture points to determine needle insertion site) for treating the symptoms 
associated with a diagnosis of chest pain or stable angina. The point prescription includes the following points: 
Conception Vessel (CV)17, Pericardium (PC)4 and Pericardium (PC)6, Stomach (ST)36, Stomach (ST)40, 
Spleen (SP)3, Large Intestine (LI)4, Liver (LV)3, Liver (LV)14, Heart (HT)7, Lung (LU)7, and Kidney (KD)6. See 
Figure for exact needling locations.  
 
c.3. Study Design. We will conduct a pilot randomized attention control trial. This design will be used to 
calculate the effect sizes for intra-individual and group differences in pain and symptoms. This design is 
superior to either placebo or sham acupuncture interventions. A placebo control design is not possible since 
neither the clinician nor participant can be blinded to the acupuncture treatment without the use of double-blind 
acupuncture needles, which are being tested in small studies and not yet commercially available62. Sham 
acupuncture, whereby needles are inserted into non acupuncture points on the body, is inferior to RCT with 
attention control design because needle punctures anywhere on the skin may be considered an ashi point; i.e. 
an active acupuncture point that may have therapeutic effects63,64. Following consent and upon admission to 
the study participants will be randomized 1:1 to the acupuncture or the attention control group. 
  
c.4. Study Team. Our study has a high probability of success because our well-qualified team has expertise in 
all facets of this study including: ischemic heart disease (Dr. DeVon), acupuncture (Dr. Schlaeger), stable 
angina, and (Dr. Shroff). Dr. DeVon has been conducting rigorous multi-site clinical research with heart 
disease populations for more than 15 years. Dr. Schlaeger is an early stage investigator with a track record of 
success in clinical trials and acupuncture studies.  
 
Figure 

 
 
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c.5. Preliminary Studies. This is a feasibility study so no preliminary data for this protocol have been  
collected. Dr. Schlaeger has recently successfully developed and tested a standardized acupuncture protocol 
for the treatment of women with vulvodynia65. Dr. DeVon, has extensive expertise in symptoms, gender, and 
measurement and has received substantial extramural (F31, T32, R15, R01) and intramural funding for her 
cardiovascular research. She has developed a validated symptom checklist for patients with acute coronary 
syndrome and has been funded on several studies to examine the acute and chronic symptoms of IHD66-68. 
 
c.6. Methods  
c.6.1. Sample & Setting. Sixty-nine women and men, with a confirmed diagnosis of chest pain or stable 
angina will be included. We will recruit women from the Chicago metropolitan area including the UIC campus 
community. Inclusion criteria are: provision of a verified diagnosis from a care provider, individual, ≥21 years of 
age (since IHD presenting as angina has not been reported in children), chest pain or intermittent angina 
symptoms (pain, pressure, or discomfort in the chest or other areas of the upper body), and medical 
confirmation of a diagnosis of stable angina. Exclusion criteria include pregnancy, , COPD causing pain or 
associated symptoms, autoimmune dysfunction, use of steroid medications, and concomitant, biofeedback,  or 
additional acupuncture. Participants will be instructed to continue medications to treat their chest pain or 
angina, as well as other health conditions, as prescribed. Etiology of chest pain or angina (i.e. occlusive 
coronary artery disease, microvascular disease, or vasospastic ischemia) is not an inclusion criteria. 
Menopausal status will be adjusted for in statistical analyses. 
 
The study will be conducted at the University of Illinois, College of Nursing (UIC CON) in clinical research 
exam rooms on the fourth floor. One Illinois licensed acupuncturist, Jun Fu, whose qualifications are described 
in the budget justification will be administering all 10 acupuncture treatments to 35 experimental participants 
(and up to 34 control group participants upon study completion) there. The exam rooms will also be utilized to 
obtain informed consent and for research data collection. The UIC CON is accessible by public transportation 
and has parking available nearby. 
 
c.6.2. Power Analysis. This feasibility pilot study is not powered to detect significant effects for improvement 
in symptom outcome measures. However, In order to achieve 80% power to detect a large effect size using 
Cohen’s classification (EF=.80), 52 patients randomized and completing the final symptoms assessments will 
be needed. Based on our sample of 26 participants, we will be able to detect a Cohen’s d effect size of 1.10 
as statistically significant. While a large effect size is not anticipated in this pilot feasibility study, an expanded 
trial will be adequately powered to explore the threshold for a clinically meaningful effect. 
 
c.6.3. Retention Strategies. We anticipate an attrition rate of no more than 10%, which means we expect a 
90% retention rate for the subjects. These numbers are based on accruals and withdrawals in Dr. Schlaeger’s 
previous 10 session acupuncture trial for which there were 36 accruals and no withdrawals. The following 
retention strategies will be employed: Participants will be engaged as active partners in the research by 
addressing possible benefits of acupuncture (experimental group) and non-pain related health education 
(control group) as well as the importance of their contribution to science. Data collection will be scheduled at 
convenient times for participants, including weekend and evening appointments. Multiple contact information 
(e-mail, cell phone, and home phone) will be collected to improve adherence to appointments. We also will 
offer $10 per visit to cover the cost of travel.  
 
c.6.4. Procedures. The research assistant will screen and consent eligible individuals. The potential 
participants will be informed that they will either be randomized to the acupuncture group (10-acupuncture 
session protocol, two treatments per week for five weeks) or the attention control group. Data will be collected 
on tablet computers before and after each session. Control group members will be offered the acupuncture 
protocol at study completion.  
 
c.6.5. Research Protocol. The research assistant (RA) will explain the nature of the study, risks and beneﬁts, 
the voluntary nature of participation, and the ability to discontinue participation at any time without 
consequences. After informed consent is obtained, participants will be randomized to the acupuncture or 
attention control group via a computer-generated random numbers table. Each number (1-26) and assigned 
group, will be written on an index card and placed in a sealed opaque envelope. The participants will select 

 
 
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one envelope from a sealed box. The participant, acupuncturist, and RA cannot be blinded to group 
assignment. All participants will complete two measures at baseline: the McGill Pain Questionnaireand the 
Seattle Angina Questionnaire-7.69 Those in the treatment group will repeat the measures following all 10 
acupuncture session. Those in the control group will repeat measures during weeks 1-5 after their attention 
control sessions. All participants will complete the AHA Angina Log throughout the study (weeks 1-5). 
Venipuncture will be performed at baseline and study completion for all participants. 
 
c.6.6. Acupuncture Protocol. The acupuncturist will swab each point with alcohol. Needles will be inserted 
and retained for 30 minutes. Each needle will be rotated 3 times to stimulate the qi in the meridian 10 minutes 
after insertion, at 20 minutes after insertion, and just prior to removal at 30 minutes. Needles will be inserted 
using the standards of clean needle technique established by the Council of Colleges of Acupuncture and 
Oriental Medicine70 One size acupuncture needle, 0.25 diameter × 40 mm length, will be used. All acupuncture 
needles are sterile, disposable, and made of surgical stainless steel with stainless steel wound heads. 
Sessions will be repeated twice weekly (with at least 2 off days in between) for 5 weeks (10 sessions).  
 
c.6.7. Acupuncture Point Prescription for Chest Pain or Angina. The standardized point prescription uses 
acupuncture points on the front of the body to enable individuals, many who are acupuncture naïve, to remain 
supine. This is aimed at reducing anxiety by enabling the participant to anticipate needle insertions.  
 
c.6.8. Attention Control Health Videos Protocol. Individuals randomized to the attention control group will 
watch health videos on broad topics not containing content that could potentially improve pain. Videos will be 
viewed from weeks 1-5 (5 timepoints) and will equate to the time the experimental group receives acupuncture 
(~10 hrs.)71. Topics include Defeating the superbugs; Can we live forever?; Do you see what I see?; Cracking 
your genetic code; How smart can we get?; Vaccines, calling the shots; Can I eat that?; and Alive inside (the 
benefits of music).The videos will be shown in the College of Nursing clinical laboratory room on the 4th floor. 
The standardized content has an additional benefit of assuring complete fidelity to the control protocol. 
 
c.7.1. Measures.   
c.7.1.a. Demographic Data Form (Appendix A). Personal characteristics will be assessed using the 
demographic data form. Standard measures including age, race/ethnicity, marital status, education, income, 
employment, and insurance are included. 
 
c.7.1.b. Protocol Acceptability Scale for Treating Angina with Acupuncture (Appendix B). The 
Satisfaction instrument is a 10-item instrument used to measure acceptability of the study processes and 
protocols. Items are measured on a 0 (negative response, i.e. did not like acupuncture) to 2 (positive response) 
scale. The protocol will be deemed to have high acceptability and have an acceptability score > 10 (80%). 
 
c.7.1.c. McGill Pain Questionnaire (MPQ) (Appendix C). The MPQ72 is a valid and reliable measure of pain.. 
The MPQ captures pain location and pain intensity on a 0 to 10 scale, where 0 is no pain and 10 is pain as bad 
as it can be andleast and worst pain in the past 24 hours.  
 
C.7.1.d. Seattle Angina Questionnaire-7 (SAQ-7) (Appendix D). The instrument consists of 7 items in 5 
domains (Physical Limitation, Angina Stability, Angina Frequency, and Quality of Life) measuring the impact 
of angina on participants’ health status. Item responses are coded sequentially from worst to best status and 
range from 1 to 6 except Quality of Life (range 1-5). Scores are generated for each domain and are scaled 0 
to 100, with 0 denoting the worst and 100 the best possible status69. The SAQ-7 was validated among 
patients presenting with stable IHD, undergoing percutaneous coronary intervention, and after acute 
myocardial infarction73. High levels of concordance (0.88–1.00) with each original SAQ domain were found. 
The SAQ-7 demonstrated good construct validity (compared with Canadian Cardiovascular Society class for 
angina; r=0.38-0.62) for patients with stable CAD.69 
 
c.7.1.e. AHA Angina Log (Appendix E). My Angina Log is a simple 1 page log used to measure each 
episode of angina. Participants are instructed to record the date and number of times they experienced angina 
as well as triggers and treatments.74 Severity of symptoms are measured on a 1-4 scale with 1 representing 
mild symptoms and 4, very severe symptoms. The instrument was designed as a clinical assessment form so 

 
 
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we will assess the psychometric properties of the Angina Log by comparing results to the SAQ-7 and the 
McGill Pain Questionnaire ®. See Table 1 for all variables, measures, and data collection time points. 
 
c.7.1.f. Massachussetts General Hospital Acupuncture Sensation Scale (MASS). The MASS Scale is a 
13-item instrument which measures the intensity of sensations (on a 0-10 scale where 0 is no sensation felt by 
the patient and 10 is an unbeartable sensation felt by the patient) when acupuncture needles are stationary or 
manipulated by the acupuncturist. This phenomenon called “de qi” is thought by many acupuncturists to be 
responsible for the therapeutic effect of acupuncture.75 
 
c.7.1.g. Biomarkers of Inflammation. Proinflammatory cytokines IL-1β, IL-2, IL-8, and IL-18; CRP76,77; and 
TNFα, the anti-inflammatory cytokines IL-4, and IL-10,76 and the dual pro/anti-inflammatory IL-678 will be 
measured to determine if there is a significant change baseline to post study (5 week). Venous blood (4.5 mls) 
will be collected in a blue-top tube containing 3.2% sodium citrate. Samples will be processed in our clinical lab 
in the college. Samples will be centrifuged at room temperature for 15 minutes; plasma will be removed into 2 
cryovials in 1 ml aliquots and stored in a -80°C freezer immediately. A label with study ID number, date, and 
time of blood draw will be placed on the cryovials prior to freezing. Samples will be batch analyzed using high-
sensitivity multiplex technologies.79 See Table 1 for all variables, measures, and data collection time points.  
 
c.8. Potential Problems, Alternate Plans, and Limitations based on the Sample Proposed. Rigorous 
research into complementary and alternative therapies has been hindered by the inability to conduct placebo-
controlled trials80. Our attention control design is a strong alternative to an intervention that cannot be blinded 
to participant or interventionalist without potential confounding treatment effects. Recruitment is always a 
potential problem with clinical research and we will enlist the help of the American Heart Association Chicago 
Affiliate and WomenHeart of Cook County to identify potential participants. Attrition is also a possible problem 
but Dr. Schlaeger has experienced very little attrition in prior acupuncture studies. We will continue to enroll to 
retain 24 participants and we will address attrition with an intention to treat analysis. Design limitations were 
addressed in section c.3. 
 
Table 1. Data Collection Variables, Measures, and Time Points (Both Groups) 
                 Variable                                            Measure/Analyses                             Data Collection Points 
                                                                                                                           (Baseline) (10 tx sessions) (5 wks.)   
Aim 1 
Recruitment 
Number enrolled/number invited to participate 
X 
 
X 
Retention 
Number retained at study completion/number recruited 
X 
 
X 
Completion 
Number of time points completed/12 (total) 
X 
 
X 
Acceptability 
Protocol Acceptability Scale for Treating Angina with 
Acupuncture 
 
 
X 
Aim 2 
Effect Size 
Intra-individual effect: mean pre-scores – mean post-
scores/pooled s.d. 
Group effect: mean differences in scores between 
acupuncture and attention control group. 
X 
 
X 
Demographic Data 
Demographic Data tionsForm 
X 
 
 
Exploratory Aim  
 
 
 
 
Biomarkers 
Interleukin 1β, 2, 6, 8, 10 & 18; CRP, TNF-α 
X 
 
X 
Outcome Measures 
Pain & Symptoms 
McGill Pain Questionnaire; Seattle Angina 
Questionnaire-7; AHA Angina Log 
X 
X 
X 
Acupuncture 
Sensations 
MASS 
 
X 
 
    Note: TX is treatment. s.d. is standard deviation. AHA is American Heart Association 
 
c.9. Statistical Analysis. Dr. Steffen will supervise data management and data analysis procedures. We will 
address missing data by intention to treat analyses (ITT), using the full information maximum likelihood (FIML) 
approach, which has been shown to produce unbiased parameter estimates and standard errors when data 
are missing at random8177767676767683. All data will be exported from RedCap and imported into SAS version 9.4 
for cleaning and analysis. All variables will be screened and descriptive statistics (frequencies, means, 

 
 
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standard deviations) will be used to describe the sample participants. Non-normal distributions may be 
optimally transformed using the Box-Cox method and/or analyzed using a comparable non-parametric test.   
                                             
c.9.1. Aim 1: To determine the feasibility of study processes (recruitment, retention, completion, acceptability) 
to inform the design and execution of a future R21 study.  
 
Hypothesis: Acupuncture therapy will be feasible (80% recruitment, retention, completion) and  
 
acceptable to individuals with chest pain or stable angina. 
For the feasibility assessments descriptive statistics will be used for describing the subject characteristics and 
recruitment, retention & completion. We will explore patient characteristics that predict attrition and/or poor 
adherence to the treatment schedule. Data collected at every session will be explored to assess change in 
pain ratings following a session and if this pattern is consistent over the course of treatment. We are interested 
in knowing if pain and other symptom relief continues to improve linearly over the 5 weeks and 10 treatments 
or if a plateau is reached suggesting the need for fewer treatments. 
 
c.9.2. Aim 2: To estimate effect sizes for pre and post intervention scores and between the acupuncture and 
attention control groups for pain/symptoms, functional status and QoL. We will estimate standardized mean 
difference effect sizes (Hedges’ g) comparing the treatment and control conditions adjusting for baseline 
differences and the upward bias due to our small sample size.  We will also compute a standardized pre-post 
difference for the treatment group. Effect sizes will be calculated for pain, angina symptoms reported via 
survey and diary, functional status, and quality of life.  
 
c.10. Timeline. We will prepare 
study materials and submit an IRB 
application upon notice of award. 
Three months is allotted for IRB 
approval process. The study is 
anticipated to begin on June 1, 
2016 and be completed on August 
31, 2017. See Table 2 for study 
timeline. 
 
References 
 
1. 
Camm AJ, Manolis A, Ambrosio G, et al. Unresolved issues in the management of chronic stable 
angina. Int J Cardiol. 2015;201:200-207. 
2. 
Wilkie DJ, Judge MK, Berry DL, Dell J, Zong S, Gilespie R. Usability of a computerized PAINReportIt in 
the general public with pain and people with cancer pain. J Pain Symptom Manage. 2003;25(3):213-
224. 
3. 
Mozaffarian D, Benjamin EJ, Go AS, et al. Executive Summary: Heart Disease and Stroke Statistics-
2016 Update: A Report From the American Heart Association. Circulation. 2016;133(4):447-454. 
4. 
Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics-2016 update: A report 
from the American Heart Association. Circulation. 2016;133(4):e38-e360. 
5. 
Longmore RB, Spertus JA, Alexander KP, et al. Angina frequency after myocardial infarction and 
quality of life in older versus younger adults: the Prospective Registry Evaluating Myocardial Infarction: 
Event and Recovery study. Am Heart J. 2011;161(3):631-638. 
6. 
Sedlak T, Izadnegahdar M, Humphries KH, Bairey Merz CN. Sex-specific factors in microvascular 
angina. Can J Cardiol. 2014;30(7):747-755. 
7. 
Berns SA, Zykova DS, Zykov MV, et al. The role of multifocal atherosclerosis in realization of new 
cardiovascular complications during one year after non ST-elevation acute coronary syndrome. 
Kardiologiia. 2013;53(8):15-23. 
8. 
Almendro-Delia M, Valle-Caballero MJ, Garcia-Rubira JC, et al. Prognostic impact of atrial fibrillation in 
acute coronary syndromes: results from the ARIAM registry. Eur Heart J Acute Cardiovasc Care. 2013. 
9. 
Wu JR, Moser DK, Riegel B, McKinley S, Doering LV. Impact of prehospital delay in treatment seeking 
on in-hospital complications after acute myocardial infarction. J Cardiovasc Nurs. 2011;26(3):184-193. 
10. 
Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics--2013 update: a report from 
Table 2. Study Timeline 
Study Phase 
(Jun-Aug 
16) 
(Sept-
Nov 16) 
(Dec-Feb 
17) 
(Mar-May 
17) 
(Jun-Aug 
17) 
Submit IRB appl. 
→ → → 
 
 
 
 
Recruit/Train RA 
 
→  
 
 
 
Data Collection 
 
→ → → 
→ → → 
→ → → 
 
Data Coding/Entry 
 
       
→ → → 
→ → → 
 
Data Analysis 
 
 
     
    → → 
 
R21 Preparation 
 
 
         
    → → 
→  
Manuscript Prep 
 
 
 
 
    → → 

 
 
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the American Heart Association. Circulation. 2013;127(1):e6-e245. 
11. 
Heidenreich PA, Trogdon JG, Khavjou OA, et al. Forecasting the future of cardiovascular disease in the 
United States: a policy statement from the American Heart Association. Circulation. 2011;123(8):933-
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