Clinical trial NCT01678586
Conditions: Pain
Keywords: Pain Pain management
Sponsor: Massachusetts General Hospital
Start date: 2012-12-01; Completion date: 2021-12-01
Enrollment: 56 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
In this aim, we propose to conduct a double blinded, placebo-controlled, and randomized clinical trial to compare the clinical effectiveness of radicular pain relief by either acupuncture therapy or a course of pain medication (e.g., Gabapentin) using Quantitative Sensory Testing (QST).

Detailed description:

Arms: arm 1: Pain subjects with radicular pain receiving 6, 30 minute acupuncture treatments. arm 2: Pain subjects with radicular pain receiving 6, 30 minute sham acupuncture treatments. arm 3: Pain subjects with radicular pain receiving gabapentin. Medication treatment groups will titrate up to the standard clinical treatment dosage for one week and maintain that dosage for 1.5 weeks. arm 4: Pain subjects with radicular pain receiving sham gabapentin. Medication treatment groups will titrate up to the standard clinical treatment dosage for one week and maintain that dosage for 1.5 weeks.
Interventions: intervention 1: Acupuncture intervention 2: Sham Acupuncture intervention 3: Gabapentin intervention 4: Sham Gabapentin
Intervention descriptions: intervention 1: In true acupuncture the needles penetrate the skin. intervention 2: In sham acupuncture the needles do not penetrate the skin. intervention 3: Gabapentin is a commonly prescribed drug used to treat neuropathic pain. intervention 4: Benadryl or diphenhydramine is used as a placebo as it could mimic some common side effects of gabapentin (i.e. sedation, drowsiness, lightheadedness)

Protocol documents:
Prot_SAP_000.pdf: 
L. Chen 
Version Date: 8/24/2015 
 
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Effect of Acupuncture and Pain Medication on Radicular Pain Using QST 
 
NCT01678586 
 
08/24/2015 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


L. Chen 
Version Date: 8/24/2015 
 
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Effect of Acupuncture and Pain Medication on Radicular Pain Using QST 
Principal Investigator: Lucy Chen, M.D. 
 
I. 
BACKGROUND 
 
a. Historical background 
Acupuncture is an ancient healing art. Like other modalities of alternative medicine, 
acupuncture has recently gained popularity as well as scrutiny in Western nations (Eisenberg 
et al., 1998; Wearn and Greenfield, 1998; Bracha, 2005; Kozak et al., 2008). Due to a 
dramatic increase in the use of acupuncture, the National Institutes of Health (NIH) convened 
a Consensus Development Conference on Acupuncture more than a decade ago, which found 
that acupuncture has been practiced by thousands of physicians, dentists, acupuncturists, and 
other practitioners for relief of pain and other health conditions (NIH Consensus, 1997). In 
2002, the World Health Organization (WHO) published a review of all clinical trials through 
1999 in which acupuncture was used (WHO, Acupuncture: Review and Analysis of Reports 
on Controlled Clinical Trials. 2002. www.who.int). The WHO summary categorizes the 
clinical data into four groups based on the data quality. A recent meta-analysis indicates that 
significant methodological differences exist with regard to the quality of clinical trials 
evaluating non-pharmacological (e.g., acupuncture) versus pharmacological treatments, 
showing a lower quality score for reports of non-pharmacological treatments than those for 
reports of pharmacological treatments (Boutron et al 2003). A subsequent study found that 
the reporting quality for acupuncture trials was significantly improved after introduction of 
STRICTA and CONSORT recommendations for the standard reporting of acupuncture trials 
(Prady et al., 2008), although these reports do not specifically address the issue of developing 
comparative and translational research tools. To date, there still lacks a standard clinical 
assessment paradigm to comparatively evaluate the efficacy of acupuncture therapy. Thus, a 
pressing issue is how to evaluate the clinical efficacy of acupuncture therapy, given the 
current trend towards evidence-based medicine using high-quality, randomized, controlled 
trials for clinical outcome measures. This issue is further complicated by the fact that pain is 
historically considered as a subjective experience that has individual variations. As such, 
evaluating the effectiveness of acupuncture in pain management presents an even more 
daunting challenge. 
 
b. Previous pre-clinical or clinical studies 
 Acupuncture has been used for clinical pain management, particularly for chronic pain 
(Carlsson et al., 2001; Leibing et al., 2002; Molsberger et al., 2002; Manhermer et al., 2005, 
2006; Cherkin et al., 2009), although its clinical outcome remains uncertain. For example, in 
a randomized, blinded, and placebo controlled trial of 131 back pain patients treated with 
acupuncture or physical therapy, acupuncture was found to be superior to controls on pain 
reduction and improvement in disability and psychological distress. When compared to the 
sham acupuncture group, however, acupuncture was only superior in reducing psychological 
distress (Leibing et al., 2002). In another prospective randomized controlled trial, 
acupuncture treatment was significantly better in pain reduction than sham controls at a 3-
month follow up (Molsberger et al., 2002), whereas other studies demonstrate a long-term 
beneficial effect (up to 6 months) after a 20-session acupuncture therapy in patients with 
fibromyalgia or neck and shoulder pain (He et al., 2004; Targino et al. 2008). Of interest to 


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Version Date: 8/24/2015 
 
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note is that there are only few head-to-head comparison studies comparing the effect of a 
medication with acupuncture on chronic pain treatment. For example, a randomized 
controlled clinical trial compared pain medication, needle acupuncture, and chiropractic 
spine manipulation on chronic (>13 weeks duration) spine pain. Patients were assessed 
before and after a treatment using Oswestry Back Pain Disability Index (Oswestry), Neck 
Disability Index (NDI), Short-Form-36 Health Survey questionnaire (SF-36), visual analog 
scale (VAS) of pain intensity and the range of movement. The highest percentage of recovery 
was found in patients receiving spine manipulation (27.3%), followed by acupuncture (9.4%) 
and medication (5%), suggesting that acupuncture does show a clinical effect comparable to 
spine manipulation or medication alone (Giles and Muller, 2003). These data indicate that 
acupuncture therapy may be beneficial in pain management, although the outcome measure 
varies from study to study. 
 
c. Rationale 
We chose gabapentin as the pain medication to be used in this study because: a) gabapentin 
has been used to treat neuropathic pain including radicular pain, b) gabapentin is a non-
opioid pain medication, which will be easy to titrate and monitor, and c) gabapentin 
attenuates hyperalgesia (exacerbated painful response to noxious stimulation) and allodynia 
(painful response to innocuous stimulation) that can be evaluated by Quantitative Sensory 
Testing (QST) (Mao and Chen, 2000). 
 
II. 
SPECIFIC AIMS 
a. Objectives and hypotheses 
In this aim, we propose to conduct a double blind, placebo-controlled, and randomized 
clinical trial to compare the clinical effectiveness of radicular pain relief by either 
acupuncture therapy or a course of pain medication (gabapentin) using QST.  The QST 
results will allow us to compare between the two treatments, thereby verifying the potential 
for alternative treatments for those with chronic neck and back pain. 
 
III. 
SUBJECT SELECTION 
a. Inclusion/exclusion criteria 
We propose to recruit subjects with cervical or lumbar radicular pain. The rationale for 
selecting subjects with cervical or lumbar radicular pain is two-fold: 1) there is a large pool 
of patients with such pain conditions and 2) a QST plate can be placed along the mirror 
distribution areas to compare the effect of acupuncture between the two sides.   Every effort 
will be made to make demographic matches (age, gender, duration of pain, etc.) among study 
groups in order to minimize study bias.  
 
Inclusion criteria:  
(1) Subject will be between ages 18 to 75 years. Both male and female subjects will be 
recruited.  
(2) Subject should have had cervical or lumbar radicular pain for at least two months. This 
requirement is to avoid the uncertainty of an unstable pain condition and to minimize the 
study variation.  
(3) Subject has a pain score of 4 or above (visual analog scale, VAS: 0 – 10 from no pain to 
worst pain).  


L. Chen 
Version Date: 8/24/2015 
 
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(4) Cervical or lumbar radicular pain will include, but is not limited to, such clinical 
conditions as disk herniation, spinal stenosis, and post-laminectomy syndrome.  
 
Exclusion criteria:  
(1) Subject has detectable sensory deficits at the site of QST. Sensory deficits refer to such 
conditions resulting from neurological diseases or medical conditions causing peripheral 
polyneuropathy and sensory changes, which include but are not limited to diabetic 
neuropathy, alcoholic neuropathy, AIDS neuropathy, severe thyroid disease, and severe 
liver or kidney disorders.  
(2) Subject has scar tissue, infection, or acute injury at the site of QST. 
(3) Subject is pregnant or nursing. 
(4) Subject tests positive for illicit drugs, marijuana, or drugs not prescribed to him/her. 
(5) Subject has a pacemaker. 
(6) Subject is currently taking gabapentin. 
(7) Subject is hypersensitive to diphenhydramine and/or gabapentin. 
 
b. Source of subjects and recruitment methods  
Study subjects will be recruited from 1) pools of pain patients under treatment at the MGH 
Center for Pain Medicine and 2) local community through advertisements and referrals. The 
MGH Center for Pain Medicine is a multidisciplinary unit including an acupuncture clinic. 
There are over 14,000 annual visits at the Center with hundreds of acupuncture visits.  
 
IV. 
SUBJECT ENROLLMENT 
a. Methods of enrollment, including procedures for a patient registration or 
randomization 
1. Study subjects will be recruited through advertisements, U.S. post, or in person 
initially by a non-study clinical caregiver at the MGH Center for Pain Medicine.  
Study subjects can contact the MGH Center for Translational Pain Research for 
information about the study.   
2. The study investigator will obtain verbal approval through colleagues from patients 
before contacting them. The patient’s attending will introduce the study, and if the 
patient is interested, study details will be explained to potential subjects by a study 
staff member.  If the subject is still interested, an initial evaluation will be conducted 
with a prepared phone-screening questionnaire. 
3. If a subject passes the initial evaluation, Visit #1 will be scheduled.  At Visit #1, the 
study protocol will be explained and all questions and concerns will be fully 
answered. 
Four groups (n=25) of subjects with cervical or lumbar radicular pain will be recruited. Study 
subjects will be assigned to one of four groups using a computer-generated randomization 
protocol (Randomization.com). 
 
b. Procedures for obtaining informed consent 
At Visit #1, the subject will meet with a study investigator (licensed as a physician and 
acupuncturist) to review and sign the consent form.  
 
c. Treatment assignment, and randomization 


L. Chen 
Version Date: 8/24/2015 
 
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One hundred subjects with cervical or lumbar radicular pain will be recruited. Potential study 
subjects will first be selected based on the general inclusion and exclusion criteria described 
above. These subjects will be randomly assigned into one of four groups (n=25): Group 1) 
subjects will receive a course of gabapentin treatment; Group 2) subjects will receive a 
course of sham drug, diphenhydramine; Group 3) subjects will receive acupuncture therapy; 
and Group 4) subjects will receive sham acupuncture. A sham acupuncture group is included 
in the acupuncture arm in order to match the design in the pain medication arm that includes 
a sham drug group as well. Study subjects will be assigned to one of four groups using a 
computer-generated randomization protocol (Randomization.com).  The subjects and 
investigators will be blinded within the medication groups (drugs vs. sham drug)/acupuncture 
groups (acupuncture vs. sham) but not between these groups.  
 
V. 
STUDY PROCEDURES  
a. Study visits and parameters to be measured 
The following are the highlights of the study protocol.  
(1) Informed consent will be obtained by a licensed physician who is also licensed in 
acupuncture. 
(2) Subjects will be randomly assigned to one of the four groups (n=25). 
(3) An initial physical examination will be performed, including Traditional Chinese 
Medicine (TCM) measurements (tongue, pulse, mood, and sleep). A urine toxicology 
screen to test for illicit drugs, marijuana, and drugs not prescribed to the subject, and a 
pregnancy test, if female subject is of reproductive potential, will be performed.  
(4) Each subject will be asked to complete a pain questionnaire, Beck Depression Inventory 
II (BDI-II), a modified McGill Pain Questionnaire and SF-36 form at three different time 
points: baseline (before any intervention), after session 3 for acupuncture or within 
treatment week 2 (e.g. day 11) for the medication group, and after session 6 for 
acupuncture or within treatment week 3 (e.g. day 18) for the medication group.  Subjects 
in the acupuncture group will be asked to fill out the Massachusetts General Hospital 
Acupuncture Sensation Scale (MASS) at visits 2-7. 
(5)  All subjects will be measured by the TCM at every office visit.  All subjects will 
complete the daily pain log throughout the treatment period of the study.   
(6) For the acupuncture group, acupuncture or sham acupuncture will be performed twice 
weekly for at least three consecutive weeks to complete a total of 6 sessions in order to 
match the total experimental period for the medication group.  
(7) For the medication group, the dosing/taper schedule will be followed as listed in the table 
below. Subjects in the medication group will receive a phone call during the titration 
phase and at the end of the taper phase. 
(8) Quantitative pain assessment (thermal QST).  The assessment will be made at three 
different time points: baseline (before any intervention), after session 3 for acupuncture 
or within treatment week 2 (e.g. day 11) for the medication group, and after session 6 for 
acupuncture or within treatment week 3 (e.g. day 18) for the medication group.  
(9) Subjects will receive up to $180 for completing the study and transportation costs will be 
covered with a $10 travel stipend for each office visit. A parking sticker for the MGH 
garages will be available upon request at each visit.  The parking sticker will replace the 
travel stipend for that visit. 
 


L. Chen 
Version Date: 8/24/2015 
 
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The following guidelines have been created for cases concerning pro-rated remuneration: 
 
1. Subjects testing positive for illicit drugs, marijuana, or undisclosed prescriptions will 
receive zero payment. 
2. Subjects who do not complete the study through their own decision will receive only 
the travel stipend for the visits attended. 
3. Subjects who are withdrawn by an investigator by no fault of their own will receive 
full payment for the visits attended.  
 
All prorated remuneration will be documented via progress notes and kept with the subject’s 
research folder. 
 
b. Drugs used 
Gabapentin or diphenhydramine (sham drug) will be used as two independent treatments in 
the medication arm. The titration schedule for each medication is shown in the following 
table. Both medications will be taken orally, and will be prepared, dispensed, and coded by 
our central pharmacy. The assignment will not be disclosed to the study subject or 
investigator.  
(1) Gabapentin 100 mg capsules will be used, which is easy to titrate. Since the 
recommended dosing interval for gabapentin is every 8 hours, a three time daily dose 
(TID) regimen will be used. Tentatively, the target daily gabapentin dose will be 900 mg 
at the end of the dose titration period.  
(2) Diphenhydramine (Benadryl; 25 mg) will be ordered as sham drug. Diphenhydramine 
could mimic some of the most common side effects of gabapentin such as sedation, 
drowsiness, and lightheadedness. Diphenhydramine has been successfully used as sham 
drug in double blind clinical trials of pain medications (e.g., Atkinson et al., 1999; 
Wallace et al., 2000). However, some uncommon side effects of gabapentin (e.g., mood 
swing) are unlikely to be mimicked by diphenhydramine. If a subject experiences mood 
swings after taking the study drug, that subject will be taken off the study medication 
accordingly.  
(3) For both gabapentin and diphenhydramine, we will use a slow titration schedule as listed 
below based on our clinical experience with both medications. When a slow titration 
schedule is used, the vast majority of patients are able to continue with these medications 
(particularly gabapentin), which will help decrease the dropout rate. (4) Because most 
pain patients are on more than one pain medication, it will be impractical to find subjects 
who are not on other pain medications (e.g., NSAIDs). Thus, other pain medications will 
be allowed but their dose should be kept unchanged during the entire experimental period 
for all subjects in both study groups.  
(5) With regard to subject compliance with the study medication, there is a lack of a practical 
method to check whether a subject has been taking the medication as instructed, 
particularly for the medications used in this study. However, we will provide study 
subjects with a log sheet to record their daily medication intake (date and time). Study 
subjects will also be asked to bring the medication bottle to each scheduled study visit 
(see below). Capsules will be counted to make sure it matches the balance between total 
capsules given and capsules taken based on the log sheet. Study medications will be 
dispensed at the initial visit and the follow-up visit in week 2 (e.g. day 11).  


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GABAPENTIN/ SHAM DRUG DOSING SCHEDULE 
Day 
Gabapentin 
AM (mg) 
Gabapentin 
Noon (mg) 
Gabapentin 
Bedtime (mg) 
Diphen. 
AM (mg) 
Diphen. 
Noon (mg) 
Diphen. 
Bedtime 
(mg) 
D1 
0 
0 
100 
0 
0 
3 
D2 
100 
0 
100 
3 
0 
3 
D3 
100 
100 
100 
3 
3 
3 
D4 
100 
100 
200 
3 
3 
6 
D5 
200 
100 
200 
6 
3 
6 
D6 
200 
200 
200 
6 
6 
6 
D7 
200 
200 
300 
6 
6 
9 
D8 
300 
200 
300 
9 
6 
9 
D9 
300 
300 
300 
9 
9 
9 
D10 
300 
300 
300 
9 
9 
9 
D11 
300 
300 
300 
9 
9 
9 
D12 
300 
300 
300 
9 
9 
9 
D13 
300 
300 
300 
9 
9 
9 
D14 
300 
300 
300 
9 
9 
9 
D15 
300 
300 
300 
9 
9 
9 
D16 
300 
300 
300 
9 
9 
9 
D17 
300 
300 
300 
9 
9 
9 
D18 
300 
300 
300 
9 
9 
9 
GABAPENTIN/ SHAM DRUG TAPER SCHEDULE 
Day 
Gabapentin 
AM (mg) 
Gabapentin 
Noon (mg) 
Gabapentin 
Bedtime (mg) 
Diphen. 
AM (mg) 
Diphen. 
Noon (mg) 
Diphen. 
Bedtime 
(mg) 
D19 
200 
200 
200 
6 
6 
6 
D20 
200 
200 
200 
6 
6 
6 
D21 
200 
200 
200 
6 
6 
6 
D22 
200 
200 
200 
6 
6 
6 
D23 
100 
100 
100 
3 
3 
3 
D24 
100 
100 
100 
3 
3 
3 
D25 
100 
100 
100 
3 
3 
3 
D26 
100 
100 
100 
3 
3 
3 
D27 
100 
0 
100 
3 
0 
3 
D28 
100 
0 
100 
3 
0 
3 
D29 
100 
0 
100 
3 
0 
3 
D30 
100 
0 
100 
3 
0 
3 
D31 
0 
0 
100 
0 
0 
3 
 
 
 


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c. Devices used 
Quantitative pain assessment:  
(1) Quantitative pain assessment will test responses to mechanical andthermal stimulation. 
We will follow the QST protocols described in previous reports (Price et al., 1994; 
Yarnitski 1997; Doverty et al., 2001; Angst et al., 2003; Koppert et al., 2003a; Reznikov 
et al., 2005; Chen et al., 2009). We chose to examine three stimulation modalities in order 
to compare and contrast the specificity of using QST to examine changes of each sensory 
modality.  All sensory and QST testing will be done on either both arms or both legs 
depending on cervical or lumbar radicular pain respectively. To evaluate the response to 
mechanical stimulation, mechanical allodynia will be examined.  
a. For mechanical allodynia, von Frey filaments will be used at the initial visit. A 
set of von Frey filaments consists of calibrated synthetic fibers. Each filament 
delivers a calibrated force when it is bent against the tested site. A series of von 
Frey filaments will be used in an ascending order to determine the threshold 
force of stimulation perceived as painful.  Each filament will be used five times.  
(2) To examine the response to thermal stimulation (thermal QST), Medoc Thermal Sensory 
Analyzer will be used. Heat/cold threshold, heat/cold pain threshold, pain tolerance, and 
windup will be examined, as these parameters are reproducible and specific based on our 
experience with QST (Price et al., 1994; Chen et al., 2009).  
a. To detect heat/cold sensation, a contact thermode will be placed to the 
designated body part. The thermode-skin interface temperature will change at 1 
ºC/sec from a baseline 32 ºC to maximum 53 ºC or a minimum of 0 ºC. Subject 
will stop the stimulation by pushing a button when the temperature change is 
first felt. This test will be repeated three times and the average value from these 
tests will be used as the heat/cold sensation (in degree Celsius).  
 
b. To detect heat/cold pain threshold, a contact thermode will be placed on the 
designated body part. The thermode-skin interface temperature will change at 1 
ºC/sec from a baseline 32 ºC to maximum 53 ºC or a minimum of 0 ºC. Subject 
will stop the stimulation by pushing a button when the pain is first felt. This test 
will be repeated three times and the average value from these tests will be used 
as the heat/cold pain threshold (in degree Celsius).  
c. To detect heat/cold pain tolerance, the same contact thermode will be placed on 
the designated body site as described above. Two types of heat pain tolerance 
will be measured. In one protocol, subject will be asked to tolerate the rising 
temperature above the pain threshold until he/she can no longer tolerate (the 
cutoff will be at 53 ºC). (This process will be repeated using cold sensations and 
the cutoff will be at 0 ºC.) In another protocol, the temperature will be preset at 
47 ºC and the subject will be instructed to tolerate the stimulation as long as 
he/she can (cutoff at 60 sec). The latency between the beginning of heat 
stimulation and the subject’s withdrawal from the stimulation will be recorded. 
In each case, the subject can withdraw from the stimulation at any time. Each 
test will be repeated three times and the values from three tests will be averaged.  


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d. To examine windup (temporal summation of second pain), a train of four 
identical stimuli at 47 ºC (supra-threshold heat stimulation), separated by a 2.2-
second interval between each stimulus, will be applied. Subject will be asked to 
rate pain intensity by VAS following each of the four stimuli. The test will also 
be repeated three times.  
(3) The Medoc QST devices are FDA approved. The MGH Bioengineering Department 
annually tests the devices for calibration and safety.  
(4) The testing will be performed according to the following sequence: mechanical allodynia 
(von Frey filaments), heat/cold sensation, heat/cold pain threshold, heat/cold pain 
tolerance, and windup, in order to minimize the confounding effect from one test to the 
next. Because subjects from all groups will be tested in this same sequence, testing bias 
will be minimized.  
(5) All tests will be performed with the examiner unaware of a treatment condition within the 
groups (true vs. sham acupuncture, gabapentin vs. sham drug), but the examiner will be 
not be blinded between the acupuncture and study medication groups. The duration for 
each QST session including all tests (mechanical, and heat/cold) will run about one hour. 
Our previous experience suggests that a subject is less likely to become distracted and the 
results are more reliable when a QST session is kept within approximately one hour.  
 
d. Procedures/surgical interventions, etc. 
(1) Acupuncture mode -- Different acupuncture modes have been used in clinical practice 
including electrical acupuncture (electroacupuncture) and manual acupuncture (e.g., Qu 
and Zhou, 2007; Kong et al., 2009). Apparently, manual acupuncture represents a more 
traditional mode of acupuncture and may be preferred in many clinical settings 
(particularly in Southeast Asian countries). In comparison with manual acupuncture,  
electroacupuncture is easy to perform and can be standardized with regard to its 
parameters and performance.  This is preferred in clinical studies aimed at examining the 
validity of QST as a tool for the acupuncture outcome assessment. Since examining 
which acupuncture mode would be more effective in clinical acupuncture therapy is not 
the primary goal of this project, we will use an effective electroacupuncture mode in our 
experiments.  
(2) Electroacupuncture parameters -- Different electroacupuncture parameters may produce 
distinct endogenous biological changes (e.g., opioid versus non-opioid-mediated 
responses) (Taguchi and Taguchi, 2007; Qu and Zhou, 2007). By the same reasoning that 
this study is not to examine the differential effect of various electroacupuncture 
parameters on clinical pain, we opt to use a modified set of electroacupuncture 
parameters that are familiar to us and have been successfully used in our practice 
including the treatment for radicular pain from disk herniation and spinal stenosis. 
Briefly, we will use the following parameters: 3 Hz (frequency), intensity tolerable to 
subject, 70 microseconds (pulse width), continuous mode, biphasic square wave, and 30-
min duration (Electroacupuncture Model ITO IC-1107). The needle size (e.g., 0.2 x 30 
mm or 0.25 x 40 mm) will be based on the choice of acupoints. For cervical radicular 
pain, we will use acupoints Fengchi (GB 20), JianLiao (SJ 14), Quchi (LI 11), Hegu (LI 
4), ShouShanLi (LI 10), WaiGuan (SJ 5). For lumbar radicular pain, we will use ShenShu 
(BL 23), QiHaiShu (BL 24), DaChangShu (BL 25), ZhuShanLi (ST 36), YanLingChaun 
(GB 34), and HuanTiao (GB 30). These acupoints are chosen based on our clinical 


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experience. We are aware that there really is not a standard choice of acupoints for a 
given clinical condition, which may be the ultimate uncertainty and mystery of 
acupuncture as an ancient healing art. Nonetheless, for the purpose of conducting 
scientific studies, we will use this set of pre-chosen acupoints in order to minimize 
clinical variations. However, adjustments can be made during the study if the chosen set 
of electroacupuncture parameters and acupoints fail to yield a satisfactory therapeutic 
effect. If any adjustment is made, the change will be applied to all study groups to ensure 
valid comparisons.  
(3) “Sham” acupuncture -- To use or not use a “sham” acupuncture control in a clinical trial 
is another controversial issue (Downs et al., 2005; McManus et al., 2007; Lundeberg, 
2008; Lund, 2009). If a sham control is to be used, which one should be chosen? If “deqi” 
is a clinical indicator of effective acupuncture, how should “deqi” be evaluated using a 
standardized protocol? While we acknowledge that examining these issues is not the goal 
of this application, we feel that including at least one type of sham acupuncture control in 
this project will help make more informed data interpretation. Among several sham 
acupuncture controls (Manhermer et al., 2005, 2006; McManus et al., 2007), we will use 
the sham control reported by Streitberger and Kleinhenz (1998).  The sham needle is 
designed so that it is not fixed inside the copper handle.  Its tip is blunt, and when it 
touches the subject’s skin a pricking sensation will be felt, simulating the puncturing of 
the skin.  The needle moves inside the handle and appears to be shortened.  The sham and 
true acupuncture procedure will be identical except that the sham acupuncture will use 
specially designed needles.  
(4) In all experiments, QST sessions will be performed by a person who will be unaware of 
the subject group assignment (e.g., acupuncture versus sham acupuncture), but the 
examiner will not be blinded of the subject’s treatment assignment (acupuncture or study 
drug).  
 
e. Data collection 
Data from descriptive assessments (e.g., McGill Pain Questionnaire, SF-36 form) will be 
collected throughout the study.  Quantitative pain assessments (e.g., QST) will be made at 
three different time points: baseline (before any intervention), after session 3 for acupuncture 
or within treatment week 2 (e.g. day 11) for the medication group, and after session 6 for 
acupuncture or within treatment week 3 (e.g. day 18) for the medication group. 
 
VI. 
BIOSTATISTICAL ANALYSES 
a. Data variables collected for the study: 
(1) Overall pain intensity and pain affect (VAS score);  
(2) Pain characteristics (e.g., burning, shooting) before and after intervention; 
(3) Mechanical allodynia (threshold force); 
(4) Heat/cold sensation, heat/cold pain threshold (degree Celsius), and heat/cold pain 
tolerance (degree Celsius and withdrawal latency in seconds) – QST;  
(5) Windup (temporal summation of second pain) – QST.  
 
b. Study endpoints: 
(1) Changes in one or more measures listed above among four groups of pain subjects – a 
between-group comparison;  


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Version Date: 8/24/2015 
 
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(2) Differences, or lack thereof, in changes between pain subjects receiving different 
interventions (e.g., acupuncture or gabapentin) – a between-group comparison;  
(3) Changes in one or more measures listed above across three time points within a given 
group (e.g., pain subjects receiving acupuncture therapy) – a within-group 
(chronological) comparison;  
(4) Differences in altered QST parameters between the affected (with radicular pain) and 
non-affected (without radicular pain) side – a within-subject comparison;  
(5) Differences, or lack thereof, in changes of QST parameters and other measures (e.g., 
overall pain intensity and pain affect by VAS score) within a given group – a within-
group comparison.  
 
c. Statistical methods: 
Specifically, we will first identify a) QST responders, b) clinical responders, and c) 
combined QST and clinical responders.  
a) QST responders refer to those subjects who show statistically significant differences in 
one or more QST parameters on the affected (with radicular pain) and/or non-affected 
(without radicular pain) side after an intervention (e.g., acupuncture or sham 
acupuncture).  
b) Clinical responders refer to those subjects who show statistically significant 
improvement in overall VAS score and/or functional status after an intervention.  
c) Combined QST/clinical responders refer to those subjects who show statistically 
significant differences in both QST (one or more QST parameters) and clinical status 
(VAS and/or functional status). 
 
We will then evaluate the similarities and differences in the response to acupuncture or 
medication as detected by QST and clinical symptom relief. The goal is to determine whether 
the analytic approach proposed for the acupuncture outcome measure in Specific Aim I & II 
would be comparable for the outcome evaluation of a medication therapy as well. For 
example, the number of responders versus non-responders in each group as well as the ratio 
of responders over non-responders in each category will be used for such comparisons. If the 
outcomes are consistent and comparable between the acupuncture therapy and medication 
therapy, it would provide additional evidence for the validity of using QST in combination 
with other clinical tools as a standardized translational tool for acupuncture research and 
clinical evaluation. 
 
d. Power analysis 
While the response in each individual study may vary, we consider 1.2 degree Celsius in 
mean pain threshold temperature, 5 seconds in mean withdrawal latency (pain tolerance), and 
a 2-point change in VAS score to be meaningful differences between study groups (Chen et 
al., 2009). Thus, a minimal sample size of 20 subjects in each group will have 80% power to 
detect such differences assuming that the standard deviation is less than 2.0 with a 
significance level of P< 0.05. We anticipate a dropout rate of 10-20%. Accordingly, we will 
use a sample size of 25 subjects for each group in our study design. If time allows us to 
expand this group size, we will increase the group size to 30 subjects per group to enhance 
the statistical power for the analyses. 
 


L. Chen 
Version Date: 8/24/2015 
 
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VII. 
RISKS AND DISCOMFORTS 
a. Complications of surgical and non-surgical procedures, etc. 
QST-related stimulation for pain threshold and pain tolerance, although transient, will elicit 
painful sensation in a study subject.  Testing for pain tolerance and acupuncture may cause 
temporary skin sensitivity similar to mild sunburn.  Subjects will be able to terminate a test at 
any time.  If skin change persists, the subject will be withdrawn and proper treatment will be 
given or be referred to a dermatologist.   
 
Acupuncture is well tolerated by most patients.  Occasionally, vasovagal responses may 
occur and subjects will be attended to immediately by a Massachusetts licensed physician.  
Infection from acupuncture is rare and aseptic procedures will be followed during the study. 
Additionally, although rare, some mild skin redness may be noted at the acupuncture sites 
after treatment. 
 
b. Drug side effects and toxicities 
The most common side effects of gabapentin are diarrhea; dizziness; drowsiness; dry mouth; 
tiredness. 
Uncommon but severe side effects that may occur when using gabapentin are rash; hives; 
itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or 
tongue; unusual hoarseness; behavior changes; confusion; difficult or painful urination; 
fever; memory problems; new or worsening mental or mood changes (eg, depression, 
agitation, anxiety, panic attacks, aggressiveness, impulsiveness, irritability, hostility, 
exaggerated feeling of well-being, restlessness, inability to sit still); new or worsening 
trouble sleeping; red, swollen, blistered, or peeling skin; severe headache or dizziness; 
suicidal thoughts or actions; swelling of the hands, legs, or feet. 
 
Diphenhydramine could mimic some of the most common side effects of gabapentin such as 
sedation, drowsiness, and lightheadedness. 
 
c. Device complications/malfunctions 
The QST device is FDA-approved and is inspected on a routine schedule established by the 
MGH Bioengineering Department. 
 
d. Psychosocial (non-medical) risks 
Uncommon but severe side effects that may occur when using gabapentin are: behavior 
changes; confusion; memory problems; new or worsening mental or mood changes (eg, 
depression, agitation, anxiety, panic attacks, aggressiveness, impulsiveness, irritability, 
hostility, exaggerated feeling of well-being, restlessness, inability to sit still); new or 
worsening trouble sleeping; severe headache or dizziness; and suicidal thoughts or actions.  
 
e. Radiation risks 
Not applicable. 
 
VIII. POTENTIAL BENEFITS 
a. Potential benefits to participating individuals 


L. Chen 
Version Date: 8/24/2015 
 
  Page 13 of 15 
There may be benefits to participating individuals with pain as acupuncture may relieve pain.  
Gabapentin is often used to treat neuropathic pain and subjects may find some pain relief 
from taking it. 
 
b. Potential benefits to society 
This study will examine a new approach to evaluating the effectiveness of acupuncture 
therapy.  This approach could be used to compare the therapeutic effects on clinical pain 
between acupuncture (other forms of alternative medicine as well) and conventional medicine 
and to advance the clinical research on alternative medicine. 
 
IX. 
MONITORING AND QUALITY ASSURANCE 
a. Independent monitoring of source data 
The data will be monitored and kept confidential at the MGH Center for Translational Pain 
Research and the HIPPA procedure will be followed for the data handling.  A department 
statistician will be monitoring the source data upon request.  
 
b. Safety monitoring 
A Data Monitoring Committee (DMC) will be formed to monitor the study progress.  The 
DMC will consist of (3-5) members with experience in opioid therapy, pain management, 
regulatory oversight, and subject safety.  The list of actual members will be provided as JIT 
information per the NIH requirement. 
 
Adverse events will be reported to the PHRC in accordance to the PHRC unanticipated 
problems including adverse events guidelines. 
 
<http://healthcare.partners.org/phsirb/adverse_events.htm>. 
 
 
c. Outcomes monitoring 
The PI will monitor study outcomes.  A monthly study staff meeting will be held to review 
the study progress and discuss any adverse event. 
 
d. Adverse event reporting guidelines 
Adverse events will be reported to the PHRC in accordance with the PHRC unanticipated 
problems including adverse events guidelines. 
 
<http://healthcare.partners.org/phsirb/adverse_events.htm>. 
 
The Beck Depression Inventory (BDI) will be scored based on the user manual to monitor 
reports of mood changes, depression, and suicidal ideation.  Study physicians will be notified 
immediately if a subject scores within the moderate to severe depression categories. Steps 
such as referring to the ED, Urgent Care Clinic, or PCP will be taken following this 
evaluation.  MGH Acute Psychiatric Services (APS) will be informed about this study and 
the possibility that such subjects may be presented to the APS. 
 
 


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  Page 14 of 15 
 
 
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