Exploring the Dose-Response Effect of Adjunctive Acupuncture on Pulmonary Rehabilitation: A Pilot Study
Phase: NA
Conditions: COPD
Sponsor: Dartmouth-Hitchcock Medical Center

 
 
Official Title: 
Exploring the Dose-Response Effect of Adjunctive Acupuncture on 
Pulmonary Rehabilitation: A Pilot Study. 
NCT number: 
NCT04947800    
Document Type:  
Study Protocol 
Date of the 
Document: 
12/19/2023 
 

PROTOCOL TITLE: Exploring the Dose-Response Effect of Adjunctive Acupuncture on 
Pulmonary Rehabilitation: A Pilot Study 
Page 1 of 20
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D-HH IRB OVERSIGHT:
One of the following must be true in order to submit to the D-HH IRB. Please check all 
that apply:
☒ The Principal Investigator is employed by D-H
☒ The study will utilize any D-H data or specimens
☒ The study will enroll D-H patients or recruit from D-H sites
☒ The study will utilize any D-H resources, e.g. study procedures will occur at 
     D-H locations and/or use of D-H equipment or shared resources
PROTOCOL TITLE:
Exploring the Dose-Response Effect of Adjunctive Acupuncture on Pulmonary 
Rehabilitation: A Pilot Study.
PRINCIPAL INVESTIGATOR:
James E Stahl, MD, CM, MPH
Department of Medicine
Telephone Number: 603 650-8529
Email Address: james.e.stahl@hitchcock.org
VERSION NUMBER/DATE:
V4 6/26/2023
REVISION HISTORY
Revision 
#
Version Date
Summary of Changes
Consent 
Change?
1
 2/13/23
Changes to consent process for control group, 
changes to intervention groups 
Yes
2
5/23/23
Addition of flyers for recruitment, 
administrative corrections
No 
3
6/26/23
Administrative correction to show group C is 
voluntary and not randomized. Addition of 
delegated RAs to assist in consenting. 
No
4 
12/19/23
Clarification on control arm being SOC 
pulmonary rehab 

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Table of Contents
1.0
Study Summary ........................................................................................................3
2.0
Objectives* ...............................................................................................................4
3.0
Background*.............................................................................................................4
4.0
Study Endpoints*....................................................................................................12
5.0
Study Intervention/Investigational Agent...............................................................12
6.0
Procedures Involved* .............................................................................................13
7.0
Data and Specimen Banking*.................................................................................15
8.0
Sharing of Results with Subjects* ..........................................................................15
9.0
Study Timelines*....................................................................................................15
10.0
Inclusion and Exclusion Criteria* ..........................................................................15
11.0
Vulnerable Populations*.........................................................................................16
12.0
Local Number of Subjects ......................................................................................16
13.0
Recruitment Methods..............................................................................................16
14.0
Withdrawal of Subjects*.........................................................................................16
15.0
Risks to Subjects*...................................................................................................17
16.0
Potential Benefits to Subjects* ...............................................................................17
17.0
Data Management* and Confidentiality.................................................................17
18.0
Provisions to Monitor the Data to Ensure the Safety of Subjects*.........................18
19.0
Provisions to Protect the Privacy Interests of Subjects ..........................................19
20.0
Compensation for Research-Related Injury............................................................19
21.0
Economic Burden to Subjects.................................................................................19
22.0
Consent Process......................................................................................................19
23.0
Process to Document Consent in Writing...............................................................19
24.0
Setting.....................................................................................................................19
25.0
Resources Available ...............................................................................................20
26.0
Multi-Site Research* ..............................................................................................20

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1.0
Study Summary
Study Title
Exploring the Dose-Response Effect of Adjunctive 
Acupuncture on Pulmonary Rehabilitation: A Pilot Study
Study Design
Wait time control with varying intervention duration
Primary Objective
Explore Adjunctive acupuncture effect on QOL and 
quantitative measures for Chronic COPD patient undergoing 
pulmonary rehab.
Secondary 
Objective(s)
-
Explore the dose response relationship between 
adjunctive acupuncture and improvement in 
pulmonary function and/or quality of life. 
-
Explore the effect of EA on inflammatory markers in 
patients undergoing PR
Research 
Intervention(s)/ 
Investigational 
Agent(s) 
Electro-acupuncture
IND/IDE # 
Study Population
Patients with severe COPD
Sample Size
30
Study Duration for 
individual 
participants
9 months 
Study Specific 
Abbreviations/ 
Definitions 
EA – electro-acupuncture
PR – pulmonary rehabilitation

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2.0
Objectives*
•
Explore Adjunctive acupuncture effect on QOL and quantitative measures for 
Chronic COPD patient undergoing pulmonary rehab.
•
Explore the dose response relationship between adjunctive acupuncture and 
improvement in pulmonary function and/or quality of life. 
•
Explore the effect of EA on inflammatory markers in patients undergoing PR
Hypotheses
•
EA will: will significantly improve QOL and quantitative measures for 
Chronic COPD patient undergoing pulmonary rehab.
•
There will be a significant dose response relationship between adjunctive 
acupuncture and improvement in pulmonary function and/or quality of life. 
•
EA will significantly reduce inflammatory markers in patients undergoing PR
3.0
Background*
Chronic obstructive pulmonary disease (COPD), is the fourth leading cause of death in the 
US (www.cdc.gov). COPD affects more than 15 million Americans. More than 140,000 
Americans die of COPD each year approximately 1 death every 4 minutes.
Though tobacco smoke is the primary cause, 1 in 4 people with COPD have never 
smoked. Their disease has resulted from air pollutants at home (secondhand smoke), at 
work (fumes). Symptoms include chronic or smoker’s cough, chronic phlegm production, 
shortness of breath, and wheezing. Early detection and treatment of COPD may change its 
course. This is usually via pulmonary function tests and chest x-ray often through the 
patients’ primary care. 
Treatment requires a careful and thorough evaluation, avoiding tobacco smoke, and 
removing air pollutants from the home and at work. As the disease progresses symptoms 
may initially be treated with medication. If the disease continues to worsen occasionally 
surgery may help, removing emphysematous areas. Another successful approach to severe 
COPD is pulmonary rehabilitation see below.
In 2015, CDC’s Morbidity and Mortality Weekly Report (MMWR), reported that rural US 
residents experienced higher rates of COPD prevalence, COPD-related Medicare-covered 
hospitalizations, and deaths than residents living in more urban counties (those with 
populations of at least 10,000 people): The percentage of adults in rural areas diagnosed 
with COPD has nearly double the percentage in large metropolitan areas. Approximately 
8% in rural areas as compared to 5% in metropolitan areas. Hospitalizations among 
Medicare enrollees for COPD were about 14 per 1000 enrollees in rural areas compared 

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with about 11 per 1000 enrollees in large metropolitan centers. Death rates from COPD 
were also greater among people living in rural areas (55 per 100,000 people) compared 
with people living in large metropolitan centers (32 per 100,000 people). New Hampshire 
and Vermont are largely rural states.
Costs
In 2010, costs attributable to having COPD were $32.1 billion and were projected to 
increase to $49.0 billion by 2020. Medicare paid 51% of those costs with 25% paid by 
Medicaid and 18% paid by private insurance in 2010. Total absenteeism costs were $3.9 
billion in 2010 with an estimated 16.4 million days of work lost because of COPD.
Dyspnea is a cardinal symptom of chronic obstructive pulmonary disease (COPD), and 
its severity and magnitude increase as the disease progresses. This can lead to significant 
disability and reduction on quality of life. Refractory dyspnea is a common and difficult 
symptom to treat in patients with advanced COPD. 
Evidence supports the benefits of oral opioids, neuromuscular electrical stimulation, chest 
wall vibration, walking aids and pursed-lip breathing in the management of dyspnea in 
the individual patient with advanced COPD. Oxygen is recommended for COPD patients 
with resting hypoxemia, though should be reserved for patients who receive symptomatic 
benefit. Up until the present the evidence has been mixed to support the routine use of 
anxiolytic medications, nebulized opioids, acupuncture, acupressure, distractive auditory 
stimuli (music), relaxation, handheld fans, counselling programs or psychotherapy(1).
What is Pulmonary Rehabilitation?
Pulmonary rehabilitation is a program of education and exercise that teach patients with 
severe COPD how to manage breathing, increase exercise tolerance and decrease dyspnea 
or breathlessness. The education part of the program teaches patient how to control their 
breathing to pace breathing with activities, how to take medicines optimally and how best 
to work with your health care team. The exercise sessions are supervised by a pulmonary 
rehabilitation staff that prepares a personalized exercise program. Typically, exercise start 
at the highest tolerable level for the patient, either sitting or standing. The amount of time 
spent exercising and the difficulty of the exercises are slowly increased with time. As you 
get stronger, and develop more endurance, breathlessness reduces.
Most Pulmonary Rehabilitation programs meet two to three times a week and programs 
can last 4 to 12 weeks or more. Program staff constantly monitor patient progress 
adjusting and increasing exercise as patients are able.

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What is Acupuncture?
Acupuncture is a method of encouraging the body to promote natural healing and to 
improve functioning through the application of needles and heat or other forms of energy 
such as electricity at specific points on the body. 
Acupuncture is one of the oldest, most commonly used medical procedures in the world. 
Though most familiar as an East Asian practice being documented in China for at least 
2000 yrs. its origins are probably much older as evidenced by the acupuncture points 
tattooed on Ötzi the Bronze Age traveler thawed out of the Austrian Alps (1991). It first 
came to general attention in the US in 1971 when New York Times reporter James 
Reston wrote about how doctors in Beijing, China, used needles to ease his abdominal 
pain after surgery. 
Acupuncture research has shown its benefit in treating a wide variety of conditions. It has 
grown rapidly in uses. In 1993, the U.S. Food and Drug Administration (FDA) estimated 
that Americans made 9 to 12 million visits per year to acupuncture practitioners and spent 
as much as $500 million on acupuncture treatments.1 In 1995, an estimated 10,000 
nationally certified acupuncturists were practicing in the United States. By the year 2000, 
that number is expected to double. Currently, an estimated one-third of certified 
acupuncturists in the United States are medical doctors.
The National Institutes of Health (NIH) has funded a variety of research projects on 
acupuncture that have been awarded by its National Center for Complementary and 
Alternative Medicine (NCCAM), National Institute on Alcohol Abuse and Alcoholism, 
National Institute of Dental Research, National Institute of Neurological Disorders and 
Stroke.
Mechanisms of Action
From the western frame, several processes have been proposed to explain acupuncture's 
effects, primarily those on pain. Acupuncture is believed to:
•Stimulate the central nervous system (the brain and spinal cord) to release 
chemicals into the muscles, spinal cord, and brain. These chemicals either change the 
experience of pain or release other chemicals, such as hormones, that influence the body's 
self-regulating systems. The biochemical changes may stimulate the body's natural 
healing abilities and promote physical and emotional well-being. 
•Conduct electromagnetic signals. Scientists have found evidence that acupuncture 
points are strategic conductors of electromagnetic signals. Stimulating points along these 
pathways through acupuncture enables electromagnetic signals to be relayed at a greater 

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rate than under normal conditions. These signals may start the flow of pain-killing 
biochemicals such as endorphins and of immune system cells to specific sites that are 
injured or vulnerable to disease.
•Activate the opioid systems: research has found that several types of opioids may 
be released into the central nervous system during acupuncture treatment, thereby 
reducing pain. Potentially also alleviating dyspnea through beta endorphin induction(2). 
•Change the release of neurotransmitters and neurohormones 
•Change the parts of the central nervous system related to sensation and 
involuntary body functions, such as immune reactions and processes whereby a person's 
blood pressure, blood flow, and body temperature are regulated.
Innovation
There are several challenges in doing acupuncture research(3).  The challenges we will 
focus on here are that of dose, response and control. The control issue is probably the best 
known of these issues. Essentially, is it possible to find a nonfunctional point on a person 
and is a sham needle truly inactive. There have been ample studies showing similar 
effects of sham needles to true or verum needles in clinical outcome at least in studies 
where the intervention and follow up are short in duration. The challenges here boil down 
to time, place and whether is there such a thing as a placebo. The time question is driven 
by the placebo effect. Almost all active clinical acts result in some improvement. If I give 
sugar pill to controls and a known anti-hypertensive to subjects, some portion of both 
arms will reduce their blood pressure and some will not, independent of the chemical 
itself. The mind is our most potent pharmacopeia we have. That said after the initial 
excitement promoting the placebo, this mind-body phenomenon tends to wane, and the 
placebo effect fades, especially if there is no further reinforcement. As a result, if one 
follows studies out long enough the placebo effect often fades while the verum treatment 
persists.
The second concern is placement. In the past, it was assumed that acupoints were precise 
with a variance within the range of a millimeter or 2 and anything placed further out 
would have no effect. Mouse models and clinical experience have shown this not to be 
true. That while acupoints may be the most effective locations for treatment there are 
often areas and zones along pathways and meridians that retain some activity even quite 
far from the target point, such as in the tendino-muscular meridians. As a result, there 
may be no part of the body that reaction free or inert.

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The third concern is the nature of the placebo effect itself. It is unclear whether any 
substance or activity that can be sensed is truly inert. Some feel the placebo effect is 
present in every medical intervention. Sugar pills have taste and texture and all activities 
touching upon the mind and body convey information and have some form of meaning. 
Meaning evokes response which can be aligned or counter the portrayed intended 
purpose of the intervention.
Our innovation, in addition to promoting improved pulmonary function with the aid of 
acupuncture. Is to explore the dose response curve of acupuncture and use a counter or 
non-inert but skew control to maximize effect size. In this case, with frail patients we do 
not wish to sedate the lung channel, which in theory could create the greatest spread in 
the acupuncture effect size. Neither do we wish to choose to be near but within the same 
tendino-muscular plane. 
Therefore, our acupuncture intervention will be EA with Lung Mu-Shu (B13, Lu2) and St 
36.
Preliminary Data
Mind body medicine and acupuncture
Acupuncture by engaging in TCM and working with mind body and spirit may be 
consider one branch of mind body medicine. Mind-body intervention have been shown to 
dramatically improve health outcomes in the cardiac arena and been shown to improve 
both metabolic as well as immune responses. (4)
Mouse/Rat models
There has been a substantial body of research into acupuncture using mouse and rat 
models. Electro-acupuncture (EA) has been noted to have a variety of effects on the 
pulmonary function, immune response, vagal system, hormone system in these murine 
models of COPD.
Inflammation:
EA intervention can improve the pulmonary function in COPD rats, which may 
be related to its effects in inhibiting inflammatory reaction, and MIF/CD 74-CD 
44/p 38 MAPK signaling pathway(5). This latter is an angiogenic pathway driven 
by macrophage inhibitory factors (MIF).
EA is associated with reducing pulmonary monocytes and lymphocytes and serum 
TNF-α, IL-6 and IL-1 β contents of bronchoalveolar fluid, suggesting an 
enhancement of immunoregulation(6)
EA can effectively suppress the increased expression of pulmonary Matrix 
metallopeptidase 9 (MMP-9), and TIMP-1, classes of enzymes that belong to the 

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zinc-metalloproteinases family involved in the degradation of the extracellular 
matrix, in COPD rats, which may contribute to its effect in improving 
pathological changes induced by COPD(7)
EA at Zusanli and Feishu improved lung function of rats with COPD and had an 
anti-inflammatory effect, which may be related to down-regulation of orexins and 
their receptors(8). Orexins [orexin-A (OXA) and orexin-B (OXB)] are two 
isoforms of neuropeptides produced by the hypothalamus. The main biological 
actions of orexins, focus on the central nervous system, controlling the sleep/wake 
process, appetite and feeding, energy homeostasis, drug addiction, and cognitive 
processes. Orexins also have neuroprotective and immuno-regulatory (i.e., anti-
inflammatory) properties.
In one study rats with COPD given EA, not only improved lung function (P<0.05) 
but were noted to have notable decreases in TNF-α and IL-1β levels (P<0.05 and 
<0.01, respectively). Orexin A, but not Orexin B, levels in lung tissue also 
decreased (P<0.01), as did mRNA expression of OX1R and OX2R in lung tissue 
(P<0.05 and P<0.01, respectively). Receptor IODs were also reduced after EA 
treatment (P<0.05). Furthermore, orexin A levels and ratio of forced expiratory 
volume in 0.3 s to forced vital capacity were strongly negatively correlated 
(P<0.01), and orexin A was positively correlated with TNF-α and IL-1β (P<0.001 
and P<0.05, respectively). 
In another study, EA resulted in a change in the balance of Thelper1/Thelper2 
cells and creating and anti-inflammatory effect as well as reducing Leukotriene 
B4 (LTB4) and NO(9). 
In a study by Zhang et al, compared with the model rats, the rats that received 
acupuncture had higher levels of TNF-α and IL-1β, A/t and BALF cell counts, 
and lung function (FEV50/FVC, FEV100/FVC, RL, Cdyn) (P<0.05). The effects 
of acupuncture were superior on the ST-36 points compared with the non-points. 
Significant correlations between lung function (FRC, RL, Cdyn) and 
inflammatory factors (TNF-α, IL-1β, IL-6, IL-8) were found (P<0.001) . TLC was 
correlated with IL-8, IL-1β and A/t (P<0.05). Plasma dopamine was correlated 
with FRC, TLC, FEV50/FVC, FEV100/FVC (P<0.05).(10)
Vagal function:
Another pathway in which EA may help COPD is through the regulation of cholinergic 
anti-inflammatory pathway (CAP). Compared with normal rats, there were a significant 
decline in lung function and discharge of the vagus nerve (P < 0.01), a sign of lung 
inflammation and an increase of ACh, AChE, IL-6 and TNF-α level in BALF or lung 
tissue (P < 0.05, P < 0.01) and higher expression of α7nAChR, JAK2, STAT3 and NF-κB 
(P < 0.05, P < 0.01) in the COPD rats. In rats receiving EA, the lung function and vagal 

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discharge were enhanced (P < 0.01), lung inflammation was improved and the levels of 
ACh, AChE, IL-6 and TNF-α were decreased (P < 0.01). Further, the expression of 
α7nAChR, JAK2, STAT3 and NF-κB was downregulated (P < 0.05, P < 0.01). The above 
effects of EA could be blocked in rats injected with α-BGT (P < 0.01)(11)
Hormonal:
The positive effect of EA on pulmonary function in COPD rats may also be related to 
downregulation of orexins and their receptors in the medulla(12)
Clinical trials
PFTs
In 2011, a RCT was conducted using acupuncture as an adjunct to pulmonary 
rehabilitation. There were 19 controls, 25 who underwent pulmonary rehabilitation, and 
16 who had both acupuncture and PR. The primary outcome measure was a change in 
measures of systemic inflammation at the end of pulmonary rehabilitation and at 3 month 
follow up. Lung function, including maximum inspiratory pressure (PiMax), quality-of-
life scores, functional capacity including steps taken, dyspnea scores, and exercise 
capacity, were secondary endpoints. There were no differences in most of the outcome 
measures between the 2 treatment groups except that subjects who had both acupuncture 
and PR remained less breathless for a longer period(13).
In a separate studies, adding transcutaneous electrical nerve stimulation therapy to 
pharmacotherapy in patients with acute exacerbation of chronic obstructive pulmonary 
disease provided clinical improvement in forced expiratory volume in 1 seconds and add 
benefit in exercise capacity (14). Acu-TENS over acupoints of bilateral EX-B-1 
(Dingchuan), BL-13 (Feishu), BL-23 (Shenshu), and ST-36 (Zusanli) improved FEV(1)% 
predicted and reduced DVAS and CAT scores on patients with stable COPD. (15, 16). In 
one study the improvement in FEV1 and dyspnea score at the end of Acu-TENS 
treatment was associated with a concurrent increase in b-endorphin level in patients with 
COPD.(17)
In a pediatric study, the acupuncture group had significantly different peak expiratory 
flow variability (p<0.01) from the control group as well as, the acupuncture group 
significantly reduced perceived anxiety (STAIC-S) at program discharge. The other lung 
function tests did not reach statistical difference(12). Duration seems to matter. In Ngai et 
al. increasing doses of AcuTENS 20, 40 and 60 min increasingly reduced decline of 
FEV(1) following exercise training in patients with asthma. (18)

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In Maa et al 45 minutes of Acu-TENS in the experimental group increased FEV1 by 0.12 
liters (95% CI 0.07 to 0.15) and decreased dyspnea by 10.7 mm (95% CI -13.9 to -7.6) on 
a VAS more than the control group. The effect on FVC was only small (mean difference 
0.05 liters, 95% CI -0.01 to 0.10).(19)
Patients with clinically stable, chronic obstructive asthma experienced clinically 
significant improvements in quality of life when their standard care was supplemented 
with acupuncture or acupressure.(8 weeks)(20)
Reduction in weight loss
In Suzuki et al , after 12 weeks, the change in body weight was significantly greater in 
the real acupuncture group compared with the placebo (mean [SD] difference from 
baseline: 2.5 [0.4] in RAG vs - 0.5 [1.4] in placebo; mean difference between the groups: 
3.00, 95% CI, 2.00 to 4.00 with ANCOVA). Patients receiving real acupuncture also had 
improvements in the results nutritional markers (RBP, PA, Tf, Hb), Inflammation 
biomarkers (TNF-α, IL-6, SAA, Hs-CRP, COHb) and the BODE index.(21),  
Acupuncture combined with aerobic training of bicycle and conventional western 
medication could prevent the reducing of BMI in patients with COPD at stable phase, 
improve pulmonary ventilation function, and increase the function of peripheral skeletal 
muscle to improve its performance.(22)
Immune response
There was a reduction in the concentration of plasma IL-6 associated with an increase in 
CD4+/CD8+ ratio in both groups, but laser was superior to inspiratory muscle training. 
IL-6 and CD4+/CD8+ were negatively correlated. Both inspiratory muscle training and 
low level laser therapy are effective physical therapy modalities in promoting immune 
disturbances.(23)
Exercise tolerance 
In Feng et al, the 6-minute walking distance measurements and health-related quality of 
life were significantly better in the real acupuncture group than that in the sham 
acupuncture group.(24) After the treatment, the scores of symptoms, life quality (CAT) 
were significantly decreased (P<0.05), while FEV 1% and FEV 1/FVC levels were 
considerably increased (P<0.05) in both groups. The effects of the test group were 
significantly superior to those of the control group in down-regulating symptom score 
and life quality score and raising FEV 1% and FEV 1/FVC levels (P<0.05). In addition, 
of the two 30 cases in the control and test groups, 10 and 18 patients experienced marked 
improvement, 16 and 10 were effective, 4 and 2 failed in the treatment, with the effective 
rates being 86.66% and 93.33%, respectively. The effective rate of acupuncture+acupoint 
application was superior medication along (P<0.05)(25)

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Exercise tolerance: the differences of 6-MWD and exercise time were statistically 
significant between groups, which were more superior in the treatment group (both 
P<0.01); the VO2max was significantly increased after treatment in the treatment group 
(P<0.05), but there was no difference between two groups (P>0.05). (2) Pulmonary 
ventilation function: the differences of FEV1%, FEV1/FVC and MVV% were 
statistically significant between groups, which were more superior in the treatment group 
(P<0.05, P<0.01); (3) SGRQ: the SGRQ was significantly improved after treatment in the 
treatment group (P<0.05), but there was no difference between two groups (P>0.05)(26)
Dyspnea
In the Suzuki RCT, it was clearly demonstrated that acupuncture is a useful adjunctive 
therapy in reducing DOE in patients with COPD. The acupuncture group had 
significantly better results on the Borg scale than the control group after 10 weeks (2.2 
+/- 2.7 versus 6.4 +/- 3.4, p = 0.0001, 95% confidence interval, -5.10 to -2.35, paired t-
test). The 6-minute walk distance and oxygen saturation at the minimum rate improved 
significantly in the acupuncture group compared with the control group.(27) After three 
weeks' treatment a traditional-acupuncture group showed significantly greater benefit in 
terms of subjective scores of breathlessness and six-minute walking distance(28),(29)
Meta-analyses 
Of the 922 articles, 12 studies were included with attesting a total of 798 participants. 
The result obtained indicated a significant improvement that favored the BAT + M group 
over the M group in CAT scores (MD: -4.77; 95% CI: -6.53 to -3.01; p < 0.00001). 
Acupuncture improved breathlessness severity in patients with advanced diseases. 
Acupuncture therapies may result in clinically important improvements in QoL and 
dyspnea(29). The methodological heterogeneity, low power, and potential morphine-
sparing effects of acupuncture as add-on should be further addressed in future trials.(31)
4.0
Study Endpoints*
Pulmonary function as measured by:
•
PFTs: FEV1, FEV1%, FVC, FVC% 
Inflammation as measured by:
•
Blood Eosinophils, Neutrophil, CRP
Quality of life as measured by:
•
Dyspnea scores (31): Borg
•
HRQOL
oSt George's Respiratory Questionnaire
oPH Q9
•
6-minute walk distance

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•
The incidence of Acute Exacerbations (AE)
5.0
Study Intervention/Investigational Agent
Acupuncture is one of the oldest, most commonly used medical procedures in the world. 
Acupuncture is a method of encouraging the body to promote natural healing and to 
improve functioning through the application of needles and heat or other forms of energy 
such as electricity at specific points on the body. Electro acupuncture uses mA electricity 
at varying frequencies for its energy input. 
There are 361 defined points in traditional acupuncture.  Most are described by a 
combination of their affiliated organ, position on the traditional meridian and their set of 
functions.  The points being used in the intervention are the Lung Mu-Shu points and 
St36 which are related to lung function and general function.  The control group will 
undergo the standard pulmonary rehab program.
The EA will be applied just prior to the patients scheduled pulmonary rehab session.
The EA generator will be placed on these points and amperage will be adjusted with 
feedback from the patient to just below the ability of the patient to sense the electricity. 
The ES intervention will be applied for 20 minutes. 
All acupuncture needles are surgical grade steel, sterile, single use and disposable.
The EA unit is the ITO ES 130. It is compliant with FDA regulations (Approved by FDA 
2008, re K081943).  This device is currently in regular use treating patients in the DHMC 
GIM Acupuncture clinic. 
This protocol does not deviate from standard of care options available to DH patients. 
DH patients will be receiving the highest standard of care in both pulmonary rehab and in 
acupuncture.
6.0
Procedures Involved*
The study will use a wait-time control design with varying intervention durations, i.e., 
dose.
Group
A
INTERVENTION- 8 weeks acupuncture 
B
INTERVENTION- 4 week acupuncture
C
SOC CONTROL-  standard of care for the study duration

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Patients will be recruited from the DHMC pulmonary rehab program. They will be 
randomized to start in group A or B with groups A and B to the EA intervention of 4 or 8 
weeks or will volunteer to be a control subject in group C.
Current practice at the DHMC pulmonary rehabilitation unit is 6 - 12 patient per rehab 
cohort. Their program is applied in 4- or 8- week increments. 
As this is a pilot, part of the study is to evaluate the facilitators and barriers to 
recruitment. For example, this protocol can be extended in time if recruitment is slow. 
We will be aiming for at least 10 participants per arm. If recruitment is robust, we will 
cap each arm at 30 participants. 
Intervention: DHMC pulmonary rehabilitation program + EA Lung Mu-Shu+ St36
Control: DHMC pulmonary rehabilitation program
EA intervention will be applied sitting for 20 minutes prior to pulmonary rehab session.
Analysis
The blinded data will be submitted to Dartmouth Synergy Clinical and Translational 
Science Institute, Biostatistics Consultation core for independent statistical analysis. 
Descriptive analysis of continuous variables will include median and interquartile range 
(IQR), or mean and standard deviation (SD) as appropriate. Categorical variables will be 
reported as counts and percentages. Baseline characteristics will be compared across all 3 
groups using Chi-square test or Fisher's exact test where appropriate for categorical 
variables and t-test for continuous variables for all enrolled participants.
Predictors of change in scores compared with baseline for outcomes each follow-up will 
be selected via stepwise general linear models with an inclusion criterion of P < 0.1 to 
enter and P > 0.05 to exit, while age and gender will be forced in the models. In addition, 
age, gender, and baseline outcomes will be included in all longitudinal outcome models. 
Outcomes analyses using changes from baseline at each follow-up, with a mixed-effects 
longitudinal regression model including a random individual effect to account for 
correlation between repeated measurements within individuals. Computations will be 
performed using SAS procedure PROC MIXED (SAS version 9.4, SAS Institute Inc., 
Cary, NC) or its equivalent. Statistical significance was defined as p < 0.05 based on a 
two-sided hypothesis test with no adjustments made for multiple comparisons.
7.0
Data and Specimen Banking*

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
NA
8.0
Sharing of Results with Subjects*
After analysis and anonymization, results will be shared with the subjects, 
their providers and public thought, oral presentations and written 
publications
9.0
Study Timelines*
The study will use a wait-time control design with varying intervention durations, i.e., 
dose.
Group
T0
T1
T2
T3
T4
T5
T6
T7
T8
T9
A
ACU
ACU
ACU
ACU
ACU
ACU
ACU
ACU
B
WAIT CTRL
WAIT CTRL
WAIT CTRL
WAIT CTRL
ACU
ACU
ACU
ACU
C
CTRL
CTRL
CTRL
CTRL
CTRL
CTRL
CTRL
CTRL
T7 + 3MOS
T7 + 6MOS
T0 will be the project start time.  T4 will be 4 weeks later.  T8 will be 3 months after the 
completion of the intervention and T9 6 months after the completion of the intervention. 
Patients will be assessed at T0, T4, T8, and T9 for functional and quality of life. 
Current practice at the DHMC pulmonary rehabilitation unit is 6 - 12 patient per rehab 
cohort. Their program is applied in 4- or 8- week increments. 
As this is a pilot, part of the study’s purpose is to evaluate the facilitators and barriers to 
recruitment. For example, this protocol can be extended in time if recruitment is slow. 
We will be aiming for at least 10 participants per arm. If recruitment is robust, we will 
cap each arm at 30 participants. 
10.0
Inclusion and Exclusion Criteria*
Inclusion Criteria: 
oPatients must be 21 y.o. of age or older and qualify to participate in the 
pulmonary rehab program at DHMC
Exclusion Criteria: 
oSevere cognitive impairment
oActive pulmonary exacerbation
oUnstable cardiopulmonary disease
oActively receiving chemotherapy 
oAdults unable to consent

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oPregnant women
oPrisoners
Patients who are randomized to groups A and B will be asked additional questions 
in preparation to receive acupuncture safely.
Patients will be randomized to one of two arms. 
11.0
Vulnerable Populations*
We will not be recruiting any vulnerable populations.
12.0
Local Number of Subjects

This is a pilot study so sample size calculation is not relevant

We will attempt to include up to 30 patients in total. This is a 
generally accepted number for pilot studies being sufficiently large 
to generate estimates in the variability in outcomes but small enough 
to be logistically efficient. 
13.0
Recruitment Methods 

Subjects will be recruited from the pulmonary rehabilitation clinic. 

Subjects will be identified and made aware of the study through their 
pulmonary providers. 

Flyers will be posted in the pulmonary rehabilitation clinical exam 
rooms to allow for self-referral for the control group as well as 
encourage conversation with their providers regarding participation 
in groups A and B.
14.0
Withdrawal of Subjects*
If subjects might be withdrawn from the study if they engage in 
disruptive behavior as defined by DHMC. We would follow 
DHMC guidelines to terminate any relations with said patient.

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If subjects leave the study for any reason, their data will be 
censored from that point onward. 
15.0
Risks to Subjects*
Acupuncture is considered a very low risk procedure.  However, there remains a 
theoretical risk of pneumothorax. Estimated risk is <  1/1,000,000 acupuncture 
treatments (Acupunct Med 2019 Dec;37(6):332-339). In order to mitigate this 
risk, all acupuncture will be provided by an experienced acupuncturist under the 
supervision of the pulmonary rehab staff in the hospital. All procedures will take 
place on hospital grounds and patients will have access to the full resources of the 
hospital in case of emergency. 
There are several potential benefits associated with program participation. Patient 
may improve clinical function and improve quality of life. 
As with other studies, there is a risk of breach of confidentiality. Confidentiality 
will be protected by using unique identification alphanumeric codes in lieu of 
names on the data documents.  Also, data will be stored in encrypted files on 
password-protected databases stored behind computer firewalls.  During the study 
sessions, participants will be reminded to keep the content of group discussions 
confidential.
Finally, there may be minor discomforts associated the acupuncture procedure 
itself, such as an occasional pinprick or small local bruise.
16.0
Potential Benefits to Subjects*

Potential benefits to subjects are improved lung function and 
improved quality of life.

They will also have the benefit of knowing they have contributed 
knowledge to benefit of society as a whole.
17.0
Data Management* and Confidentiality
The blinded data will be submitted to Dartmouth Synergy Clinical and 
Translational Science Institute, Biostatistics Consultation core for independent 
statistical analysis. 
Descriptive analysis of continuous variables will include median and interquartile 
range (IQR), or mean and standard deviation (SD) as appropriate. Categorical 
variables will be reported as counts and percentages. Baseline characteristics will 
be compared across all 3 groups using Chi-square test or Fisher's exact test where 

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Pulmonary Rehabilitation: A Pilot Study 
Page 18 of 20
v.12.19.2023
appropriate for categorical variables and t-test for continuous variables for all 
enrolled participants.
Predictors of change in scores compared with baseline for outcomes each follow-
up will be selected via stepwise general linear models with an inclusion criterion 
of P < 0.1 to enter and P > 0.05 to exit, while age and gender will be forced in the 
models. In addition, age, gender, and baseline outcomes will be included in all 
longitudinal outcome models. Outcomes analyses using changes from baseline at 
each follow-up, with a mixed-effects longitudinal regression model including a 
random individual effect to account for correlation between repeated 
measurements within individuals. Computations will be performed using SAS 
procedure PROC MIXED (SAS version 9.4, SAS Institute Inc., Cary, NC) or its 
equivalent. Statistical significance was defined as p < 0.05 based on a two-sided 
hypothesis test with no adjustments made for multiple comparisons.
This is a pilot study so power analysis is not applicable.
All collected data will be anonymized and stored on password protected hard 
drives behind the hospitals firewall. Only the PI or his designee will be allowed 
access to the data. At the end of the study all key tables mapping identifiable data 
to unique identifiers with be erased.  All data will be kep in compliance with 
DHMC data policies. 
18.0
Provisions to Monitor the Data to Ensure the Safety of Subjects*
The research team will be in email communication and meet on an as needed 
basis during the recruitment, enrollment and intervention phases of the study to 
ensure that recruitment targets are met, to ensure the quality and thoroughness of 
the data being collected at baseline, and to confer regarding questions or concerns 
that arise during the program implementation. Following completion of the 
intervention portion of the study, the team will meet bi-weekly to address issues 
concerning data entry and analysis, to manage follow-up assessments, and to 
discuss results and reporting. 
This time will also be used to identify any safety issues or untoward events that 
may arise.  Reports will be filed with the IRB in case such an event occurs and we 
will comply with DHMC and IRB policies, procedures and recommendations in 
this regard
19.0
Provisions to Protect the Privacy Interests of Subjects

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As with other studies, there is a risk of breach of confidentiality. Confidentiality 
will be protected by using unique identification alphanumeric codes in lieu of 
names on the data documents.  Also, data will be stored in encrypted files on 
password-protected databases stored behind computer firewalls.  During the study 
sessions, participants will be reminded to keep the content of group discussions 
confidential. In the case of a privacy breach, all DH policies and procedures will 
be adhered to.
20.0
Compensation for Research-Related Injury
Not Applicable
21.0
Economic Burden to Subjects
Not Applicable
22.0
Consent Process

Consent will take place in the exam rooms of the pulmonary rehab clinic 
or the Clinical Research Unit for groups A and B with Dr. Stahl, delegated RAs or 
a Clinical Research Unit RN conducting the consent process. Standard operating 
procedures SOP: Informed Consent Process for Research (HRP-090)” will be 
followed.

For Group C a waiver or alteration of consent process will be requested to 
allow for the option of verbal consent as no intervention will be included, a CRC 
from the CRU will provide this consent. The consent process will be documented 
in the EMR the same as written consent. 
23.0
Process to Document Consent in Writing

Standard operating procedures will be followed for obtaining 
consent. (see “SOP: Written Documentation of Consent (HRP-091))
24.0
Setting

All procedures will be conducted in the offices and exam rooms of 
DHMC including the pulmonary rehab clinic at 5C, Clinical 
Research Unit at 4M, and the Cardiac and Pulmonary Rehab gym.  
Telehealth visits for the control group will be conducted at the 
subject’s discretion. 
25.0
Resources Available
The research will be conducted by the PI, co-PI and their 
designees
Recruitment: see above

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Research plan: see above 
Pulmonary rehab specialist, pulmonary rehab nurse, pulmonary 
rehab therapist, nutritionist.  Exercise equipment
Acupuncture team- physician acupuncturist.
Pulmonary rehab classes consist of two sessions per week for 8 
weeks, depending on individual needs. Class size: 6 to 10 
individuals per class 
All research staff will have had to complete the CITI program 
26.0
Multi-Site Research*
Not applicable