Local Effects of Acupuncture on the Median and Ulnar Nerves in Patients With Carpal Tunnel Syndrome
Phase: NA
Conditions: Carpal Tunnel Syndrome
Sponsor: Oregon Health and Science University

Study Product Guidelines and Considerations 
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Version 1.0 
 
 
29 MAR 2012 
Local Effects of Acupuncture on the Median and Ulnar Nerves in Patients 
with Carpal Tunnel Syndrome: A Pilot Mechanistic Study 
 
NCCIH Protocol 
 
Alexandra Dimitrova, MD, MA, Charles Murchison, MS, Yunpeng Luo, DAOM,  
 Jau-Shin Lou, MD PhD, Barry Oken, MD, MS 
 
 
Study Principal Investigator:   
Alexandra Dimitrova, MD, MA 
Assistant Professor of Neurology  
Oregon Center for Complementary and Neurologic Disorders (ORCCAMIND) 
Oregon Health & Science University 
 
Supported by:  
The National Center for Complementary and Integrative Health (NCCIH) 
 
NCCIH Grant number 1K23AT008405-01: “Electrophysiologic Study of Acupuncture's Effect 
on the Peripheral Nervous System” 
 
 
  
 

Study Product Guidelines and Considerations 
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Version 1.0 
 
 
29 MAR 2012 
Tool Revision History 
Version Number: 1 
Version Date: February 15, 2015 
Summary of Revisions Made: N/A 
Version Number: 2 
Version Date: June 25, 2015 
Summary of Revisions Made:  
Minor edit to Blinding – section 3.4 
Changes to section 4.4 – Stratified randomization 
Minor edits to section 5.2 – Experimental Procedures Timeline 
Changes to section 9.1 – Sample Size Calculations 
Changes to section 9.4 – Statistical Analysis Plan 
 
 
Version Number: 3 
Version Date: July 27, 2015 
Summary of Revisions Made:   
Minor edits to section 9.1 – Sample Size Calculations 
Minot edits to section 9.4 – Statistical Analysis Plan 
Version Number: 
Version Date: 
Summary of Revisions Made:  

 
 
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TABLE OF CONTENTS 
Page 
Local Effects of Acupuncture on the Median and Ulnar Nerves in Patients with Carpal 
Tunnel Syndrome: A Pilot Mechanistic Study .......................................................................... 1 
Tool Revision History ................................................................................................................ 2 
TABLE OF CONTENTS ............................................................................................................ 3 
STUDY TEAM ROSTER .......................................................................................................... 6 
PRÉCIS ...................................................................................................................................... 8 
1. STUDY OBJECTIVES .......................................................................................................... 10 
1.1. Primary Objective ............................................................................................................. 10 
1.2. Secondary Objectives ........................................................................................................ 10 
2. BACKGROUND AND RATIONALE ................................................................................. 10 
2.1. Acupuncture Background ................................................................................................. 10 
    2.2. Significance………………………………………………………………………………11 
    2.3. Innovation………………………………………………………………………………...11 
    2.4. The “DeQi” Sensation and the Peripheral Nerves………………………………………..12 
    2.5. Introduction to Acupuncture Modalities – Manual and Electroacupuncture…………….12 
2.6. Quantitative Sensation Testing…………………………………………………………...12  
2.7. Study Rationale…………………………………………………………………………..13 
    2.8. Pilot Data…………………………………………………………………………………14 
3. STUDY DESIGN .................................................................................................................... 15 
    3.1. Study Subjects……………………………………………………………………………16 
    3.2. Study Site…………………………………………………………………………………16 
    3.3. Experimental duration and followup……………………………………………………..16 
    3.4. Blinding…………………………………………………………………………………..16 
4. SELECTION AND ENROLLMENT OF PARTICIPANTS ............................................. 17 
4.1. Inclusion Criteria .............................................................................................................. 17 
4.2. Exclusion Criteria ............................................................................................................. 17 
4.3. Study Enrollment Procedures ........................................................................................... 19 
    4.4. Stratified Randomization………………………………………………………………...19 
    4.5. Accrual Plan……………………………………………………………………………...19 
 
5. STUDY INTERVENTIONS………………………………………………………………..20 
5.1. Week 1 Baseline QST and NCS testing…………………………………………………20 
 
5.1.1. Baseline QST Measurement……………………………………………………...20 
 
5.1.2. Baseline Nerve Conduction Studies...………………............................................21 

 
 
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5.1.3. Acupuncture Delivery……………………………………………………………22 
5.2. Experimental Procedure Timeline………………………………………………………24 
5.3. Adherence Assessment  .................................................................................................... 25 
6. STUDY PROCEDURE/EVALUATION SCHEDULE .......... Error! Bookmark not defined. 
7. SAFETY ASSESSMENTS .................................................................................................... 26 
7.1. Adverse Events and Serious Adverse Events ................................................................... 27 
    7.2. Subject Follow up and Protection against Risk………………………………………….27 
7.3. Adverse Event Tracking and Reporting - Data and Safety Monitoring Plan ................... 27 
8. INTERVENTION DISCONTINUATION ........................................................................... 28 
9. STATISTICAL CONSIDERATIONS ................................................................................. 28 
9.1. Sample Size Calculation ................................................................................................... 28 
    9.2. Stratified Randomization - see Section 4.4 
9.3. Outcome Measures and Statistical Hypotheses, as outlined in the Specific Aims ........... 30 
    9.4. Statistical Analysis Plan……………………………………………………………….....30 
9.5. Interim Analyses and Stopping Rules ............................................................................... 32 
10. DATA COLLECTION AND QUALITY ASSURANCE ................................................. 32 
10.1. Data Collection Forms and Participant Confidentiality .................................................. 32 
10.2. Data Management ........................................................................................................... 33 
10.3. Quality Assurance and Training ..................................................................................... 33 
    10.4. Protocol Deviations ......................................................................................................... 33 
    10.5. Monitoring ...................................................................................................................... 33 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY .................................................. 33 
11.1. Institutional Review Board (IRB) Review ...................................................................... 33 
11.2. Informed Consent Forms – see Appendix A and section 4.3 ......................................... 34 
    11.3. Inclusion of Women and minorities…………………………………………………….32 
11.4. Participant Confidentiality – see 10.1 ............................................................................. 34 
11.5. Study Discontinuation ..................................................................................................... 34 
12. PUBLICATION OF RESEARCH FINDINGS ................................................................. 34 
13. REFERENCES ..................................................................................................................... 33 
14. APPENDIX A – Study Forms ............................................................................................. 38 
I. Subject Screening Form – pg. 37-39 
II. Lay Language Protocol Summary – pg.40-41 

 
 
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III. OHSU Consent and Authorization Forms:  
Clinical Research Consent Summary – pg. 42-43 
 
Clinical Research Consent Form – pg. 44-48 
HIPAA Clinical Research Authorization – pg. 49-50 
IV. Data Form 51-53 
 
 

 
 
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STUDY TEAM ROSTER  
Alexandra Dimitrova, MD, MA – Principal Investigator 
Oregon Health & Science University 
Oregon Center for Complementary and Alternative Treatments in Neurologic Disorders 
(ORCCAMIND) 
3181 SW Sam Jackson Park Road, Mail Code CR 120 
Portland, OR 97239 
tel. (503) 494-0744 
fax. (503) 494-0966 
email: dimitroa@ohsu.edu 
 
Charles Murchison, MS 
Oregon Health & Science University 
Parkinson Center of Oregon 
Department of Neurology, OP-32 
3181 SW Sam Jackson Park Road 
Portland, Oregon 97239-3098 
Phone: (503) 494-7231  
Fax: (503) 494-9059 
Email: murchiso@ohsu.edu 
 
Tabatha Memmott, BA/BS 
Oregon Health & Science University 
ORCCAMIND 
Same contact info as Dr. Dimitrova 
Email: memmott@ohsu.edu 
 
Diana Dimitrova, PhD 
Oregon Health & Science University 
ORCCAMIND 
Same contact info as Dr. Dimitrova 
Email: dimitrov@ohsu.edu  
 
Yunpeng Luo, DAOM, LicAc 
Oregon Health & Science University 
Center for Women’s Health 
808 SW Campus Dr, Portland, OR 97239 
Phone: (503) 418-4500    
Fax: (503) 494-1678  
Email: luoy@ohsu.edu 
 
Annette (Zoe) Fallian, MS, LicAc 
Oregon Health & Science University 
ORCCAMIND 
Same contact info as Dr. Dimitrova 
Email: fallian@ohsu.edu 

 
 
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Jau-Shin Lou, MD, PhD, MBA 
University of North Dakota School of Medicine and Health Sciences 
700 1st Avenue S 
Fargo, ND 58103 
Phone: (701) 234-4036 
Fax: (701) 234-4151 
Email: jaushin.lou@med.und.edu 
 
Barry Oken, MD, MS 
Oregon Health & Science University 
ORCCAMIND 
Same contact info as Dr. Dimitrova 
Email: oken@ohsu.edu 

 
 
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PARTICIPATING STUDY SITE - Oregon Health & Science University (OHSU) 
PRÉCIS  
Study Title: Local Effects of Acupuncture on the Median and Ulnar Nerves in Patients with 
Carpal Tunnel Syndrome (CTS): A Pilot Mechanistic Study 
 
Objectives: The purpose of this study is to measure the local effects of acupuncture on the 
median and ulnar nerves in patients with median neuropathy at the wrist (carpal tunnel 
syndrome), using nerve conduction studies (NCS) and quantitative sensory testing (QST) as 
outcomes. Our secondary aim is to compare acupuncture’s effect on the functioning of a diseased 
nerve (median nerve in CTS) to its effect on a healthy nerve (ulnar). Additionally, we aim to 
compare the local, nerve-specific effect of manual acupuncture to that of low-frequency 
electroacupuncture and of high-frequency electroacupuncture.  
 
Design and Outcomes: In a mechanistic study of acupuncture, 60 subjects with carpal tunnel 
syndrome (CTS) will be randomized to manual acupuncture (MA), low-frequency 
electroacupuncture (LF-EA) and high-frequency electroacupuncture (HF-EA) groups. Baseline 
measurements will consist of QST (vibration and cold detection thresholds), as well as NCS of both 
median and ulnar nerves. Then, each group will undergo acupuncture to the median nerve 
(Pericardium channel points) and to the ulnar nerve (Heart channel points), one week apart, order 
counterbalanced, followed by post-acupuncture NCS and QST measurements in both nerves (See 
Figure 1 below).  
During the study initial visit (Week 1) baseline QST and NCS measurements will be obtained, 
followed by acupuncture (manual, low- or high-frequency) intervention to the ulnar or to the 
median nerve (based on treatment randomization) and repeat post-intervention QST and NCS 
measurements to both median and ulnar nerves.  
During the study second and final week (Week 2), baseline QST and NCS measurements will be 
obtained again, followed by acupuncture (MA, LF-EA, HF-EA) intervention to the nerve, which 
was not treated the first week. Finally, repeat post-acupuncture QST and NCS measurements will 
be obtained in both median and ulnar nerves (see Figure 1 below). 
Interventions and Duration : Subjects will be randomized to 3 intervention groups as specified 
above: Manual, Low-frequency and High-frequency electroacupuncture. Each subject will 
receive the following interventions:  
1. Acupuncture to PC3, 5 overlying the median nerve 
2. Acupuncture to HT3,4  overlying the ulnar nerve 
These will be performed one week apart, in random order. Each acupuncture session will involve 
2 needles, with active treatment time 20 min and needle retention during the subsequent QST 
measurement. Needles will be taken out prior to the post-acupuncture NCS measurements.   
 
 
 
 
 
 

 
 
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Fig.1. Study Procedures Flowchart 
 
Abbreviations: NCS=nerve conduction studies, QST=quantitative sensory testing, CDT=cold detection 
threshold, VDT=vibration detection testing, MA= manual acupuncture, LF-EA=low-frequency 
electroacupuncture, HF-EA=high-frequency electroacupuncture, MN = median nerve, UN = ulnar nerve 
 
Sample Size and Population: We plan to enroll 60 subjects with mild-moderate carpal tunnel 
syndrome, ages 18-75, male and female. In addition to basic eligibility criteria described in detail 
below and based on a subject’s medical history, we anticipate the need to screen 75-80 subjects 
in the lab with baseline QST and NCS in order to make the determination for study eligibility 
(see Figure 1 above). Subjects will be recruited from OHSU’s EMG lab and neuromuscular 
clinic.  

 
 
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Once determined eligible and meeting the baseline QST and NCS enrollment criteria, subjects 
will be randomized using stratified randomization (with stratification factors of age and gender), 
to 3 groups of 20 subjects each - Manual Acupuncture (MA) group, Low-frequency 
Electroacupuncture (LF-EA) group and High-frequency Electroacupuncture (HF-EA) group.  
1. STUDY OBJECTIVES 
1.1. Primary Objective 
Specific Aim 1: Characterize the effects of acupuncture on QST (cold and vibration sensation 
thresholds) and nerve conduction study parameters in the Median and Ulnar nerves. 
Hypothesis: Acupuncture will cause decrease in cold and vibration detection thresholds (improve 
sensation) in the underlying nerve sensory distribution only. Acupuncture will cause NCS changes, 
characteristic of improved nerve function. 
 
1.2. Secondary Objectives 
Specific Aim 2: Compare the effects of acupuncture on a diseased nerve (Median) to those of a 
healthy nerve (Ulnar), using QST (cold and vibration sensation thresholds) and NCS 
parameters. 
Hypothesis: There will be greater change in cold and vibration detection thresholds and NCS 
parameters in the median nerve compared to the ulnar, due to the lower functional baseline of the 
median nerve. 
 
Specific Aim 3: Compare the effects of manual acupuncture to those of low-frequency and 
high-frequency electroacupuncture.    
Hypothesis: High-frequency electroacupuncture will have greater effect on NCS, QST followed by 
low-frequency electroacupuncture and manual acupuncture, in accordance to traditional practices. 
2. BACKGROUND AND RATIONALE 
2.1. Acupuncture Background  
Acupuncture is an ancient therapeutic modality, traditionally involving needling techniques, 
based on ancient Chinese theories of acupoints located along energy channels called meridians. 
More recently acupuncture has emerged as an important integrative medical treatment, both in 
the hospital and outpatient setting (1, 2). In 1998 an NIH Consensus Development Panel 
concluded that acupuncture is efficacious in adult post-operative and chemotherapy-induced 
nausea and vomiting, and that acupuncture is helpful in other conditions, including stroke 
rehabilitation (3). More recent evidence-based reviews have shown the therapeutic benefits of 
acupuncture for chronic low-back pain (44, 45), migraine and tension headache (46, 47), 
chemotherapy-induced nausea and vomiting (48), among other conditions.   
 
In spite of acupuncture’s increased acceptance, its mechanism of action remains unknown. There 
is debate as to whether there is point-specific response in acupuncture or whether it induces a 
more generalized response, perhaps related to endogenous opioid or placebo response. Early 
research suggested that the effects of acupuncture are mediated on a systemic level by the 
endogenous opioid system (4, 5, 6). Acupuncture seems to increase cerebrospinal fluid levels of 
endorphins, enkephalins, and adrenocorticotropic hormone and its effect can be blocked by the 
endorphin antagonist naloxone (4, 6). The immune effects of acupuncture seem to be mediated 

 
 
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via increased activity of splenic NK cells and levels of interferon-gamma (7). Acupuncture may 
also affect the gene expression of neuropeptides and their receptors (8, 9). A centrally acting 
agent/mechanism, however, cannot explain why acupuncture is conventionally applied in close 
proximity to the locus of pain and why the analgesic effects of acupuncture are often limited to 
the ipsilateral side (10, 11).  
 
For many decades acupuncture practitioners and anatomists have attempted to correlate the 
location of acupuncture points to peripheral nerves, spinal segments and spinal plexuses (12-17, 
18). This neuroanatomical theory of acupuncture suggests that acupuncture’s effect is mediated 
via afferent input through the peripheral nervous system, eliciting a reflex at the level of the 
spinal cord via the sympathetic plexuses and via efferent to the visceral organs and skeletal 
muscle (19, 20).  The neurophysiologic testing to support these theories is lacking so far and 
further study on the local effects of acupuncture on the peripheral nervous system is needed. 
There is a consensus, however, that the nervous system is vital in processing the effects of 
acupuncture. 
 
2.2. Significance  
The lack of understanding of acupuncture’s mechanism of action is a major obstacle to its wider 
acceptance. The lack of objective physiologic measurements of acupuncture’s effect has posed 
many difficulties in designing acupuncture research studies involving dose response and 
efficacy. 
 
Our research will address this knowledge gap by measuring the local effects of acupuncture on 
an underlying nerve by focusing on Nerve Conduction Study (NCS) parameters and Quantitative 
Sensory Testing (QST) in the territory of that nerve. Additionally, we will isolate these effects by 
comparing them to those of a neighboring nerve. Quantifying acupuncture’s effects using 
physiologic parameters and discreet values could standardize treatment regimens and measure 
therapeutic effect in tangible ways. As acupuncture practices vary widely, with various treatment 
modalities and point selection, the ability to measure direct effects on the peripheral nerves may 
help compare treatment regimens and standardize practices by developing efficient protocols.  
 
This line of research is expected to substantiate the proposed association between acupuncture 
meridians and peripheral nerves in the arm and leg and translate the explanatory constructs of 
channels and Qi, drawn from TCM into an acceptable western physiologic paradigm of nerve 
physiologic changes based on redistribution of charge. 
 
2.3. Innovation 
While fascia changes have been implicated in chronic pain conditions (50), likely mediated by a 
local inflammatory response, the analgesic effects of acupuncture cannot be explained by fascia 
changes alone, without involvement of the nervous system. Langevin and Sherman (51) recently 
hypothesized that acupuncture causes changes in mechano- and nociceptive receptors in 
connective tissue. Recent histological studies of fascia have shown it to be very rich in Ruffini 
and Pacinian corpuscles and free nerve endings and it is therefore believed to be involved in 
proprioception (32). The proposed research is innovative, in our opinion, because it does not 
seek to disprove or adopt the fascia mechanistic theory of acupuncture, but rather focuses on the 

 
 
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peripheral nervous system’s processing of acupuncture as a final common pathway before further 
mediation and potentiation occur at the level of the spinal cord and cerebrum.  
 
QST and NCS have both been used in acupuncture research before, however their use has been 
to assess therapeutic clinical improvements in the patient (21, 42). These measurements have 
never been targeted to a particular nerve distribution and used to study anatomical correlations 
between acupoints/channels and an underlying peripheral nerve, with the goal of assessing for 
acupuncture-induced functional changes in the nerve. We hope that this line of research will lead 
to a cohesive understanding of acupuncture’s mechanism of action, which incorporates the fascia 
and the peripheral nervous system effects.  
 
2.4. The “DeQi” Sensation and the Peripheral Nerves 
According to traditional acupuncture teachings, it is essential to elicit a sensation called “DeQi”, 
in order to achieve therapeutic results. This sensation is accomplished by manipulation of the 
acupuncture needle after its insertion in the acupuncture point. It has been described as aching, 
soreness, heaviness/pressure, fullness, warmth, coolness, tingling, numbness and dull pain at the 
site of the needle (29) or radiating paresthesias (30). It appears that this sensation is mediated by 
the peripheral nerves. In clinical practice patients often report that manipulation of the 
acupuncture needles causes a sensation “like hitting one’s funny bone” and neuropathy patients, 
when undergoing acupuncture of local points in the feet, liken the sensation to an exacerbation of 
their neuropathy symptoms. Langevin et al (31) have suggested that the sensation of DeQi is 
elicited by fascia manipulation, however muscle fiber contraction surrounding the needle 
remains a possibility. From a neurologic perspective, both muscle or fascia manipulation would 
result in mechanical compression and possibly release of inflammatory factors, leading to small 
and larger peripheral nerve fiber activation.  
 
2.5. Introduction to Acupuncture Modalities – Manual and Electroacupuncture 
Manual acupuncture consists of placing needles in acupuncture points, at a point-specific pre-
determined depth, based on established guidelines from the Traditional Chinese Medicine 
literature. Following insertion the needles are manually manipulated with rapid clockwise or 
counter-clockwise rotation or small vertical adjustments in the scale of millimeters. This 
manipulation (aka needle stimulation) is carried out for 45 sec – 1-2 minutes, typically until the 
subject feels the “De Qi’ sensation. The needles are then left in for 15-20 minutes. Often times a 
second stimulation session is performed midway in the course of the treatment, depending on the 
acupuncturist’s style of practice.  
 
Electroacupuncture is an acupuncture modality, which gained wide acceptance in the 1950s 
simultaneously in China, Germany and Japan (43). It consists of placing acupuncture needles in 
traditional acupuncture points, then connecting them to an electrostimulating device. Electrical 
current is applied to connect 2 needles to an anode and cathode. Typically alternating current in 
the range of 10-80 milliamps is applied, with a voltage range of range of 40-80 volts. Frequency 
varies from 2-100 Hz. In general lower frequencies (2-10Hz) are considered to be 
toning/stimulating of the nerves and higher frequencies (80-100 Hz) are considered inhibitory 
and are used for analgesia (43). Typical electroacupuncture treatment usually lasts 10-20 
minutes.  
 

 
 
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2.6. Quantitative Sensation Testing (QST) 
Computer-assisted Sensory Evaluation (CASE) aka Quantitative Sensation Testing (QST) has 
been in clinical use since the late 1970s, when Dyck, O’Brien et al introduced the concept of an 
automated system to evaluate touch-pressure vibration and thermal cutaneous sensation (38). 
QST is administered in a lab and consists of standardized, precisely delivered computer-
generated stimuli, based on careful study of physiologic perception thresholds and “just 
noticeable difference (JND)” of heat, cold, vibration and touch-pressure (39). Typically the 
lateral side of the nail bed is used to assess vibration detection threshold (VDT) in the hand and 
the dorsal surface of the hand is used to assess cooling (CDT) or heating detection threshold.  
 
                         
 
Fig.2. CASE IV Vibration Stimulator 
 
      Fig.3. CASE IV Thermal Stimulator 
 
The creators of the CASE system created various algorithms for assessing hyper- and 
hypoalgesia in peripheral neuropathy patients. QST performed with the fourth generation system 
(CASEIV) have been shown to be efficient, reproducible, and validated against other algorithms 
of sensory testing (40). The correlation coefficients for vibratory detection threshold (VDT) and 
cooling detection threshold (CDT) have been found by greater than 0.9 (40). While QST has 
become a widely-used research tool, the validity of its results is highly dependent on the 
subject’s ability to cooperate and sustain focused attention on stimulus presentation. Therefore, 
QST cannot be administered when the patient is inattentive, uncooperative, demented, sedated, 
or too ill to cooperate. 
 
2.7. Study Rationale - Acupuncture for Carpal Tunnel Syndrome, PC6 and the Median 
Nerve 
One area of acupuncture research, which has yielded successful results, is the efficacy of 
acupuncture in the treatment of Carpal Tunnel Syndrome (CTS). Acupuncture has shown to be 
effective for mild-moderate CTS with lasting effects on Nerve Conduction Studies (NCS) a year 
post-treatment (21). Additionally, laser acupuncture and TENS applied to the wrist has been 
shown to be effective in the treatment of CTS, with symptom improvement still present on 1-3 
year follow-up (22, 23). Interestingly the above treatment protocols all involved acupuncture 
regimens with needles placed in the Pericardium channel (PC), most commonly PC6 (21, 24) and 
PC7 (21, 22, 23, 25) and PC3 (25), see Figure 4 below.  
 
Fig.4. Anatomical Correlation of the Pericardium Meridian/Channel and the median nerve 

 
 
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The anatomical connection of the acupuncture point PC6 and the Median nerve has been well 
established both in cadavers (26) and in live subjects using ultrasound (27, 28), most strikingly 
with a documented case of the acupuncture needle piercing through the Median nerve sheath, 
with absence of any symptoms in the subject (28).  
 
All these studies raise the question of the effect of acupuncture in the Pericardium channel on the 
underlying Median Nerve.  
 
2.8. Pilot Data 
So far we have shown that the procedure is safe, tolerable and capable of producing the projected 
outcome variables in an accurate and consistent manner. We have achieved lab consistency in 
QST and NCS outcome measures. We have completed testing of 3 pilot subjects with the 
following findings: 
 
Pilot 1: 65 yo woman with moderate CTS. Treated with HF-EA to Median nerve (Week 1), 
followed by HF-EA to Ulnar nerve (Week 2). Cold detection threshold in the Median nerve 
territory improved with acupuncture from 13.1 to 8.7 units. Ulnar territory cold detection was 
unchanged with acupuncture. Median nerve compound muscle action potentials (CMAP) 
amplitude at the wrist and elbow increased with acupuncture by a third, whereas Ulnar CMAP 
were unchanged with acupuncture. She reported symptomatic improvement at Week 2. 
 
Pilot 2: 69 yo man with moderate CTS. Treated with HF-EA to Median nerve (Week 1), 
followed by HF-EA to Ulnar nerve (Week 2). No significant changes were seen in QST with 
acupuncture, however the subject had new Sensory Nerve Action Potentials (SNAP) in the 
Median nerve during Week 2, which were absent in Week 1 prior to acupuncture intervention. 
He also had symptomatic improvement at Week 2.  
 
Pilot 3: 43 yo woman with moderate CTS. Treated with HF-EA to Median nerve (Week 1), 
followed by HF-EA to Ulnar nerve (Week 2). Both cold and vibration detection threshold in the 
Median nerve territory improved with acupuncture (12.5 to 8.4 and 8.7 to 3.9, respectively). 

 
 
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Median motor nerve conduction velocity increased from 54.5 to 59.3 m/s with acupuncture. 
Median sensory nerve conduction velocity (NCV) increased from 42.3 to 50.2 m/s in Week 1 
during treatment. Ulnar sensory NCV did not change in Week 1, but increased from 66.7 to 78.6 
m/s in Week 2 with treatment, with an associated Ulnar SNAP increase. Of note, after Week 2 
this subject was completely symptom free and remained so 2 months after the conclusion of the 
study (she called the lab). 
3. STUDY DESIGN 
This is a pilot mechanistic study in which the local effects of acupuncture on the median and 
ulnar nerves will be investigated, by applying acupuncture to points in the Pericardium and Heart 
meridians, which appear to track the path of the median and the ulnar nerves, respectively (see 
Figure 5 below). All subjects will have a diagnosis of carpal tunnel syndrome, which is a 
median nerve entrapment at the wrist.  
 
Subjects will be randomly allocated to one of 3 intervention groups – manual acupuncture (MA), 
low-frequency electroacupuncture (LF-EA) and high-frequency electroacupuncture (HF-EA). All 
subjects will have a diagnosis of carpal tunnel syndrome (median nerve entrapment at the wrist). 
The intervention will be acupuncture (MA, LF-EA or HF-EA) and the outcome variables – post-
acupuncture NCS of the median and ulnar nerves and quantitative sensory testing (QST) 
measurements in the palmar median and ulnar nerve distributions (specifically cold and vibration 
detection thresholds), see Figure 1 above. In each group there will be 2 treatments in random 
order, in which acupuncture will be applied to the median nerve/Pericardium meridian and the 
ulnar nerve/Heart Meridian. 
 
Fig.5. Anatomic correlation of the median nerve and Pericardium Channel (PC) and of the 
ulnar nerve and Heart Channel (HT).  
 
 
 
 
The healthy ulnar nerve will serve as a control in two ways:  
1. Local Effects - the ulnar nerve, being in close proximity to the median nerve, will be 
investigated for possible effects when acupuncture is delivered to Pericardium channel points 
(over the median nerve). In this way we will explore whether acupuncture has effects only on the 
underlying nerve, or also on a neighboring nerve. This will be accomplished by measuring post-
acupuncture QST and NCS in both the median and ulnar nerves, when the intervention is done 
over the median nerve.  

 
 
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Hypothesis: Acupuncture will cause decrease in cold and vibration detection thresholds (improve 
sensation) in the underlying nerve sensory distribution only. Acupuncture will cause NCS changes, 
characteristic of improved nerve function. 
 
2. Healthy vs Diseased nerve Effect – The intervention will be delivered over the ulnar nerve 
(healthy) as well, using Heart channel acupuncture points. This will enable us to compare the 
acupuncture effect on a healthy nerve, compared to a diseased nerve (Median nerve in patients 
with CTS).  
Hypothesis: There will be greater change in cold and vibration detection thresholds and NCS 
parameters in the median nerve compared to the ulnar, due to the lower functional baseline of the 
median nerve. 
 
Our third goal involves comparison among the 3 intervention groups , specifically we aim to 
compere the effects of manual acupuncture (MA) to those of low-frequency (LF_EA) and high-
frequency electroacupuncture (HF-EA).    
Hypothesis: High-frequency electroacupuncture will have greater effect on NCS, QST followed by 
low-frequency electroacupuncture and manual acupuncture, in accordance to traditional practices. 
 
3.1. Study subjects 
60 subjects with carpal tunnel syndrome will be randomized to 3 intervention groups as 
described above with stratification for age and gender. Subjects will be both male and female, 
ages 18-75. Subjects will be recruited from OHSU’s EMG lab and neuromuscular clinic.  
 
3.2. Study site 
OHSU will be the only study site for this protocol 
 
3.3. Experimental duration and follow-up 
Study procedures will be carried out over 2 consecutive weeks (see Figure 1). As this is a 
mechanistic study involving immediate effects of acupuncture on a peripheral nerve, there will 
be no follow up period beyond Week 2. This study employs 3 commonly practiced, well 
established interventions, which are considered low-risk: nerve conduction studies (NCS), 
quantitative sensory testing (QST) and acupuncture to the forearm. Subjects will be given all 
necessary follow-up contact information in case of unanticipated adverse events, as described in 
Section 7 (Safety Assessments).  
 
3.4. Blinding  
As this is a mechanistic study comparing acupuncture to acupuncture intervention, it is 
impossible to blind subjects in the conventional sense. Depending on a subject’s knowledge of 
anatomy and acupuncture, however, a subject may or may not be aware as to which nerve is 
targeted for intervention on each week.  
 
All QST assessments will be performed in blinded fashion and the investigators assessing the 
outcome measures will not be delivering the intervention (acupuncture). QST assessments will 
be performed by a blinded investigator (Tabatha Memmott), who will be seated behind a screen 
with the subject’s arm, needles and QST probes not visible. The PI will not be involved in QST 
measurements. Additionally, the PI will be blinded to the acupuncture intervention, which will 
be delivered by a licensed acupuncturist (Annette Fallian or Yunpeng Luo).  

 
 
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Week 1 QST and NCS baseline will be assessed in non-blinded fashion, prior to randomization.  
Following these initial measurements, the PI will screen the subject for Secondary Exclusion 
criteria. Once the subject is determined eligible, the PI will leave the room. PI will be blinded to 
randomization (MA, LF-EA or HF-EA) and treatment assignment (median or ulnar nerve). 
Randomization will be performed by the study acupuncturist and the other investigators will be 
blinded to it.  
 
The PI will return to the room once the acupuncture intervention has been completed, the post-
acupuncture QST measurements obtained and acupuncture needles removed, in order to perform 
the post-acupuncture NCS and remain blinded to the intervention. 
4. SELECTION AND ENROLLMENT OF PARTICIPANTS  
4.1. Inclusion Criteria 
Participants must meet all of the following inclusion criteria to participate in the study: 
 
• Age 18-75 
• Both male and female subjects 
• Presence of mild-moderate sensorimotor or sensory median neuropathy, established by pre-
existing NCS/EMG study AND 
• Baseline NCS study within the past 2 years, consistent with mild-moderate median 
entrapment neuropathy (CTS) defined as meeting any of the 3 conditions below (33, 34): 
1. Prolonged distal Median sensory AND/OR motor latency  
2. Reduced Median sensory nerve action potentials (SNAP) amplitude by no more than 50% 
3. Amplitude of the compound muscle action potential (CMAP) recorded from APB  > 50% 
of normal  
• Presence of neuropathy symptoms consistent with CTS for at least 3 months (36) 
4.2. Exclusion Criteria 
Patients will be excluded on initial screening in the EMG lab or the Neuromuscular clinic at 
OHSU based on the following Exclusion Criteria: 
 
Conditions in which acupuncture/electroacupuncture may be contraindicated: 
• Coagulopathy/ Current anti-coagulation treatment 
• Epilepsy 
• History of CAD or pacemaker insertion 
• Pregnancy 
• Presence of any skin condition in the arm, such as dermatitis, bruises, weeping skin, skin 
lesions, infected skin, or necrotic skin. 
Conditions in which QST testing may be contraindicated: 

 
 
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• Significant cognitive impairment such as diagnosis of Alzheimer’s disease or Mental 
Retardation or any other condition interfering with alertness, attention and ability to 
participate in QST 
• Hospitalization for anxiety or depression in the past 3 months 
• Current psychiatric diagnoses (other than anxiety or depression) 
• Illicit drug use in the past month 
• Current EtOH abuse (> 2 drinks/day) 
• History of significant neurological disease which may affect sensation, e.g., strokes, Multiple 
Sclerosis, or spinal cord disorder 
• Change in neuropathy medications within the past 2 months 
• Change in opioid, benzodiazepines, SSRIs or other sedating medications in the past 2 months 
Conditions, which predispose to generalized neuropathy  
• Abnormal thyroid function tests (by history) 
• Past chemotherapy treatment 
Other Contraindications: 
• History of wrist or elbow fracture, past arm trauma, loss of fingers, scarring  
• History of carpal tunnel release surgery or any other surgery on the arm or shoulder 
• History of arthritis 
• Use of any investigational drugs within the previous six months 
Exclusion Criteria based on NCS within the past 2 years: 
• Presence of isolated motor Median neuropathy (absence of sensory neuropathy on NCS or 
absence of sensory symptoms) 
• Severe neuropathy symptoms leading to inability to tolerate acupuncture or QST 
• Presence of Severe Carpal Tunnel Syndrome, defined as: 
1. Absent sensory nerve action potential recorded from the second or fifth digit. 
2. The amplitude of the compound muscle action potential recorded from the APB or 
ADM is less than 50% of normal (< 2.5 mv) 
• Presence of Ulnar neuropathy 
• Presence of Martin-Gruber anastomosis  
Secondary Exclusion Criteria after WEEK 1 Baseline QST and NCS measurements (See 
Figure 1): 
• Failure to comply with QST due to inattentiveness, etc 
• Hyperalgesia on QST  
• Hypoalgesia on QST  
• Inability to confirm diagnosis of mild-moderate CTS (normal NCS) 
• Inability to tolerate NCS/QST  
• Presence Severe CTS   

 
 
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• Pure Motor Median Neuropathy  
• Ulnar Neuropathy  
4.3. Study Enrollment Procedures  
Potential participants will be identified through screening OHSU’s EMG lab and neuromuscular 
clinic patient schedules. Basic eligibility screening will be conducted using OHSU’s electronic 
medical record database (EPIC). Patients, who pass this medical record screening will be 
approached by the PI. If a patient is interested, the PI will explain the objectives, risks and 
benefits of the study. At this point if a patient agrees to screening, the PI will proceed with an 
evaluation based on medical history, habits and recent (within last 2 years) EMG/NCS. The 
screening results will be documented using the Subject Screening Form (Appendix A). If a 
potential subject is determined to be eligible, the PI will answer all his/her questions, inform the 
subject that he/she may withdraw consent at any point and obtain informed consent for the study. 
This will involve presenting the subject with a Lay Language Protocol Summary and an OHSU 
Consent-and-Authorization form (as required by OHSU IRB) is also included in Appendix A.  
 
Following enrollment, subjects will come to the lab for initial screening, consisting of QST and 
NCS. Following this testing, if they pass the Secondary Exclusion Criteria, subjects will be 
randomized to MA, LF-EA and HF-EA, using a computer-generated stratified randomization 
based on age and gender.  
 
4.4. Stratified Randomization 
Subjects will be randomized to the 3 intervention groups, using a specially-designed computer 
program which will enable stratified randomization based on 2x2 categories where one category 
is gender (M/F) and the other is projected median age split of 56, based on age of enrolled pilots 
and clinic patients with carpal tunnel syndrome (18-56/57-75).  
 
Gender and age have confounding effect on proper estimation of NCS and QST as they vary by 
age and sex. Specifically, men tend to have faster nerve conduction velocities (NCV) and larger 
nerves than women and with age NCV declines and sensory thresholds, measured by QST tend 
to rise (38, 49, 55, 56). Randomization will be performed by study acupuncturist, and all 
outcome assessors will be blinded to it.  
 
The randomization program is also designed to offer random order of acupuncture intervention 
location (median vs ulnar nerves), with a built-in ability to assign 50% of subjects within a group 
to median nerve first and the other 50% - to ulnar nerve first.  
 
4.5. Accrual Plan  
Subjects will be recruited from OHSU’s EMG lab as the lab follows rigorous electrodiagnostic 
criteria for CTS diagnosis. Such criteria are usually lab-specific and take years to develop. 
Additionally, a recent EMG is crucial as CTS tends to fluctuate and has a relapsing-remitting 
course for most patients. We plan to recruit subjects in the EMG lab, immediately after 
completion of their NCS/EMG. The EMG lab at OHSU sees anywhere from 12-20 CTS subjects 
per month. Our experience with recruiting pilot subjects has been that patients are interested in 
the study as even 2 sessions may improve CTS symptoms and often times the alternative is more 
invasive such as carpal tunnel release surgery.  

 
 
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Of the 12-20 CTS patients seen in the lab many would not meet the eligibility criteria or would 
not be able to participate for reasons listed above – travel, logistics, surgery, etc. We have had 
great success recruiting patients local to the Portland area with mild-moderate CTS so far. 
 
Once the protocol is approved we anticipate enrollment of 2-4 subjects per month. This number 
varies due to seasonal patient volume and staffing fluctuations in the EMG lab. Other factors in 
recruitment are: EMG lab patients who are not local to Portland and unwilling to travel for study 
purposes, patients who are scheduled for carpal tunnel release surgery and who wish to proceed 
with surgery without delay for study participation, patients who have severe carpal tunnel 
syndrome, rising prevalence of marijuana use (including medical marijuana), anatomic variants 
or other conditions making patients ineligible for the study and lastly patients who simply are not 
interested in participation.  
 
An overly conservative estimation of 2 subjects per month who meet all criteria including 
baseline testing in the lab would translate into 24 subjects per year and a 2.5 year period of 
recruitment and data collection. We have capacity to test 4-5 subjects per month and will plan to 
do so, if we are able to recruit this number.  
 
5. STUDY INTERVENTIONS (See Figure 1 – Study Procedures Flowchart) 
 
5.1. Week 1 Baseline QST and NCS testing 
5.1.1. Baseline QST Measurement 
Patients will be tested for vibratory detection threshold (VDT) and cold detection (CDT) using 
the CASEIV system, described above.  
 
VDT 
Vibration Stimuli will be delivered as 25 discrete levels ranging from 0.0 to 350 micrometers 
(μm) of displacement, based on previously established “Just Noticeable Difference” (JND) 
values (38). Each stimulus is presented with an exponential onset, and turns off with an 
exponential decay, in order to eliminate the touch-pressure artifact, which is caused by 
an instantaneous on/off. Stimulation will be delivered to the 2nd digit finger pad  (median 
distribution) and the 5th digit finger pad (ulnar distribution), with the hand stretched out 
supinated (palm facing up) on an even surface.  
 
CDT 
The Thermal Stimulator use a four‑degree‑per‑second ramp up and down, and is typically 
operated in a range from 8 degrees to 50 degrees C., with an accuracy of 1.25 to 0.25 degrees C., 
depending on temperature. For high-magnitude thermal (cooling) stimuli, the absolute 
temperature is limited to 8 degrees C. Thermal stimuli are approximately 6 seconds in duration. 
CDT will be assessed over the thenar eminence (median distribution) and hypothenar eminence 
(ulnar distribution) with the hand on an even surface, supinated and palm facing up.  
 
The 4, 2 and 1 stimulus presentation algorithm (to be used both for VDT and CDT) 

 
 
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The 4, 2, 1 stimulus presentation algorithm was developed by Dyck et al (41) as a more time-
efficient alternative to forced choice, as it enables investigators to assess the sensory threshold in 
a given sensory modality in 2-5 minutes in most cases. 
 
Testing will begin at an intermediate level (level 13 of 25). The stimulus will be increased (if not 
felt) or decreased (if felt) by four steps to the point of turnaround (felt at the higher level when 
not felt at lower levels, or not felt at the lower level when it had been felt at the higher level). 
After the first turnaround, stepping will be in steps of two. After the second turnaround, stepping 
will be by steps of one. A total of 20 stimulus events will be used, with five of them being 
randomly distributed null stimuli. If three consecutive failures are observed at level 25, testing 
will be terminated, and the subject will be classified as insensitive (QST hypoalgesia). If three 
consecutive successes were observed at level 1, testing will be terminated and the subject was 
classified as supersensitive (QST Hyperalgesia). Five null stimuli will be randomly interspersed 
among 15 non-null stimuli. A positive response (indicating perception) to more than one null 
stimulus will abort the program. The subject will be re-instructed, and the test will be re-run. 
Three failures (due to spurious answers to null stimuli) when the test is re-run twice after the test 
is initially aborted will indicate that the algorithm could not be used for this subject and the 
subject will be excluded from further participation in the study. 
 
Following baseline QST subjects who can comply with and tolerate QST, have no hypo-or 
hyperalgesia will undergo baseline NCS studies.  
 
5.1.2. Baseline Nerve Conduction Studies (NCS) 
Following informed consent (obtained during subject screening), baseline nerve conduction 
studies will be performed according to OHSU’s EMG laboratory procedures and in accordance 
with well established guidelines, as described by Kimura (49). These nerve conduction studies 
are standard clinical procedures in evaluating patients with neuromuscular diseases and will be 
performed using the Dantec Keypoint® G4 Workstation (Natus Medical Incorporated). Subject 
skin temperature will be maintained above 32 C, using a heating pad to warm up a cold hand if 
needed.  
 
Specifically, the following nerve conduction studies will be performed: 
a. Median Nerve Conduction Study:  
We will measure the sensory nerve action potential (SNAP) amplitude from the second 
digit, the compound muscle action potential (CMAP) amplitudes from the Abductor 
Pollicis Brevis, the motor and sensory distal latency, and the nerve conduction velocity in 
the forearm (from the elbow to the wrist). 
b. Ulnar Nerve Conduction Study:  
We will measure the sensory nerve action potential (SNAP) amplitude from the fifth 
digit, the compound muscle action potential (CMAP) amplitudes from the Abductor 
Digiti Minimi, the motor and sensory distal latency, and the nerve conduction velocity in 
the forearm (from below elbow to the wrist) 
 
Following baseline NCS, subjects who pass the Secondary Exclusion criteria (have mild-
moderate CTS by electrodiagnostic criteria, are able to tolerate NCS, lack pure motor neuropathy 
or ulnar neuropathy), will be randomized as described above.  

 
 
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Subjects who meet the Secondary Exclusion criteria after Week 1 baseline QST and NCS testing 
will exit the study without being randomized and will be compensated for their time, as stated in 
the OHSU Consent-and-Authorization form (Appendix A).  
 
5.1.3. Acupuncture Delivery (See Figure 1) 
Studies will be randomized to 3 acupuncture modalities (MA, LF-EA and HF-EA). Within each 
group, a subject will receive 2 acupuncture sessions – one in Week 1, the other in Week 2, in 
random order either to the median or to the ulnar nerve. This separation into 2 sessions is 
necessary as there may be residual post-acupuncture effects on the first treated nerve, interfering 
with isolating the true effects of acupuncture on the subsequently treated nerve.  
 
Acupuncture will be applied by an experienced licensed acupuncturist (Annette Fallian or 
Yunpeng Luo), using sterile single-use acupuncture needles (DBC Spring Ten 0.25x30 mm, 
0.25x40 mm, DongBang Corp, Korea). In all 3 intervention groups, a DeQi sensation will be 
elicited after penetration of the skin in a depth of 3-5 mm. In the manual acupuncture group, a 
second stimulation will be given midway through the session by manual rotation/manipulation of 
the needles.  
 
In the electroacupuncture groups (LF-EA and HF-EA) such manipulation will not be possible, 
however electrical stimulus intensity will be adjusted so that the subjects continues to feel the 
electricity-caused paresthesias/DeQi throughout the treatment period. In both electroacupuncture 
modalities pulse duration will be 60 microseconds, on a continuous frequency. Electroacupuncture 
will be was performed by using an electrical device (Electrostimulator 6c.Pro, Pantheon Research, 
Venice, CA – See Figs 6, 7) with insulated cable clamps connected to the acupuncture needles. 
 
For LF-EA, a frequency of 2 Hz will be used and for HF-EA- frequency of 100 Hz. Stimulus 
intensity will be increased and re-adjusted, so that the patient feels the stimulation strongly, but 
not painfully (2–8 mA). This will be done as each 5 minutes the patients will be asked to rate the 
intensity of the electrical sensation on a scale from 1-10, with desired range 6-7/10. Adjustments 
to stimulus intensity will be done so that it is perceived at 6-7/10 throughout the course of 
electroacupuncture treatment. Each acupuncture treatment will last 20 minutes. 
 
Fig.6. Electroacupuncture delivery using Pantheon 6c Electrostimulator 
 
 
 
 

 
 
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Fig. 7. Pantheon 6c Pro Electrostimulator 
 
 
For the median nerve acupuncture treatment (MA, LF-EA or HF-EA) the insertion points 
will be on the Pericardium Channel (PC3 and PC5), which are used to stimulate the channel 

 
 
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(Water-Metal point) according to traditional 5-element acupuncture theory (see images below). 
PC3 and PC5 are closely anatomically associated with the median nerve (see Figure 5). 
   
  Fig.8. Acupuncture point PC3 (Pericardium 3)  
Fig.9. Acupuncture point PC5 (Pericardium 5) 
 
 
For the ulnar nerve acupuncture treatment (MA, LF-EA or HF-EA) the insertion points will 
be on the Heart Channel (HT3 and HT4), which are used to stimulate the channel (water-metal 
points) according to traditional 5-element acupuncture theory (see images below). HT3 and HT4 
are closely anatomically associated with the ulnar nerve (Figure 5).  
 
Fig.10. Acupuncture point HT3 (Heart 3)   
            Fig 11. Acupuncture point HT4 (Heart 4) 
 
 
  
 
5.2. Experimental Procedure Timeline (Figure 1) 
During Week 1, enrolled and consented subjects will come to the lab for Week 1 Baseline QST 
and NCS testing as outlined above. During this baseline testing subjects will be introduced to the 
QST equipment and will undergo assessment of baseline cold detection threshold (CDT) and 
vibration detection threshold (VDT), as well as baseline NCS as outlined above. This would take 
approximately 1.5 hours and both procedures are non-invasive.  
 

 
 
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Following assessment of Baseline QST and NCS, subjects will be screened for Secondary 
Exclusion criteria, which relate to their CTS diagnosis and ability to tolerate NCS and QST 
(Figure 1). Subjects who do not pass the Secondary Exclusion Criteria will exit the study, with 
proper documentation of why they were ineligible.  
 
Those who pass the Secondary Exclusion Criteria will be randomized to MA, LF-EA and HF-
EA, as well as undergo random treatment assignment of median (PC3, PC5) or ulnar (HT3, HT4) 
nerve. Following randomization a subject will undergo acupuncture for 20 minutes involving 2 
needles as outlined in detail above.  
 
Following acupuncture, Week 1 Post-acupuncture QST (CDT and VDT) and NCS will be 
obtained in a manner analogous to the Week 1 Baseline QST and NCS testing outlined above. 
QST will be obtained first, with the needles retained in position, followed by needle removal and 
conduction of NCS. This will conclude Week 1. Total estimated time of Week 1 procedures is 4-
4.5 hours. Subjects will be provided with water, bathroom break/other breaks as needed and a 
healthy snack.  
 
Week 2 procedures will occur exactly one week after Week 1, as close to the same time of day 
as possible. Week 2 will start with Week 2 Baseline QST and NCS testing, following the same 
methodology as the Week 1 Baseline QST and NCS outlined above, although subjects will not 
be screened for inclusion/exclusion criteria at Week 2. A second baseline is necessary because in 
our experience even a single intervention to PC3, PC5 or HT3, HT4 may alter NCS and QST 
parameters or the median and ulnar nerves, respectively.  
 
Once Week 2 Baseline QST and NCS testing is obtained, acupuncture will be delivered to the 
nerve not treated during Week 1. For example, if a given subjects is randomized to LF-EA and 
randomly assigned to ulnar nerve acupuncture in Week 1, the same subject will be administered 
LF-EA to the median nerve in Week 2, following Week 2 Baseline QST and NCS (Figure 1).  
 
After the acupuncture intervention, Week 2 Post-acupuncture QST (CDT, VDT) and NCS will 
be obtained in a manner analogous to those obtained in Week 1. Following completion of Week 
2 NCS, subjects will complete and exit the study. Total testing time for Week 2 is estimated to be 
3.5-4 hours.  
 
Data will be recorded using the study Data Form (Appendix A). 
 
5.3. Adherence Assessment  
We do not anticipate problems with adherence as acupuncture will be delivered in the lab during 
both study visits. It is possible that some subjects will exit the study after Week 1, in which case 
we will include their results from Week 1 in the analysis.  

 
 
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6. STUDY PROCEDURE/EVALUATION SCHEDULE 
Procedure 
SCREENING 
 (in EMG Lab or 
Neuromuscular 
Clinic) 
WEEK 1   
WEEK 2 
Medical Record Screening 
x 
 
 
EMG/NCS review of prior study (up to 2 yrs 
old) 
x 
 
 
Prospective Subject Interview 
x 
 
 
Study Screening by PI 
x 
 
 
Screening Form 
x 
 
 
Enrollment and OHSU Consent-and-
Authorization Form 
x 
 
 
Lay Language Protocol Summary form 
x 
 
 
Baseline QST and NCS 
 
x 
x 
Screening for Secondary Exclusion Criteria 
by PI 
 
x 
 
Randomization and Random Treatment 
Assignment 
 
x 
 
Data Form 
 
x 
x 
Acupuncture Intervention 
 
x 
x 
Post-acupuncture QST and NCS 
 
x 
x 
Study Completion and Exit 
 
 
x 
Adverse Events  
 
X 
X 
7. SAFETY ASSESSMENTS  
Acupuncture holds the risk of minor bleeding/ecchymoses, especially in coagulopathic patients 
or those taking anti-platelet agents. Placing needles in the area of the median or ulnar nerves may 
lead to nerve damage by the needles, however the acupuncture points described above (PC3,5 
and HT3,4) are commonly used and well established as safe over centuries of acupuncture 
practice. Furthermore, the needle used in acupuncture is 30G and solid (non-hollow), which 
minimizes underlying tissue damage. Electroacupuncture causes small, rapid muscle contractions 
surrounding the needles, which can feel unpleasant, but is not painful or harmful. In clinical 
practice patients routinely undergo acupuncture without any need for follow-up, unless a 
problem arises.   
 
NCS testing is unpleasant to most patients, however holds no health risk. QST is widely 
considered safe and non-invasive.  

 
 
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7.1. Adverse Events and Serious Adverse Events 
Assessment of acupuncture’s safety is typically observation based. Adverse events typically 
occur as a result of treatment or in the few days immediately post-treatment. There are no lab 
values or other parameters, which could assure acupuncture safety. 
 
An adverse event (AE) is defined as any unfavorable and unintended diagnosis, symptom, sign 
(including an abnormal laboratory finding), syndrome or disease which either occurs during the 
study, having been absent at baseline, or if present at baseline, appears to worsen. Adverse 
events will be recorded regardless of their relationship to the study intervention.  
  
Examples of unanticipated adverse events involving acupuncture are: infection at the 
acupuncture needling site, moderate-severe bruising and bleeding at the acupuncture site, 
moderate-severe pain and discomfort after acupuncture, new onset of weakness or numbness, 
permanent worsening of carpal tunnel syndrome symptoms.  
 
A serious adverse event (SAE) is defined as any untoward medical occurrence that results in 
death, is life threatening, requires inpatient hospitalization or results in persistent or significant 
disability/incapacity.  
 
7.2. Subject Follow up and Protection against Risk  
All subjects will be given Dr. Dimitrova’s contact number and encouraged to report any 
concerns and complications during the 8-day study period and following completion of the study. 
In the unlikely event that acupuncture causes lasting discomfort, bothersome ecchymoses, 
worsening of carpal tunnel and neuropathy symptoms, Dr. Dimitrova will be available for urgent 
assessment and treatment. If the patient needs further neurologic or other care, they will be 
referred to Dr. Dimitrova’s clinic or to one of the other providers in the neuromuscular division 
or another appropriate clinician within OHSU. The informed consent will clearly state that a 
subject may discontinue participation in the study at any time.  
 
As with all human subject investigations at OHSU, any adverse events will be reported to the 
IRB and there is a Data and Safety Monitoring Plan in place (see details below). 
 
7.3. Adverse Event Tracking and Reporting - Data and Safety Monitoring Plan  
There is a Data and Safety Monitoring Plan (DSMP) in place for the IRB-approved study “Local 
effects of acupuncture on the Median and Ulnar nerves in patients with Carpal Tunnel 
Syndrome”, in accordance with OHSU IRB’s recommendations and guidelines.  
 
According to this IRB-approved DSMP, an independent study safety monitor has been 
appointed – Dr. Tessa Marburger. The independent monitor is a neuromuscular expert and has 
no conflict of interest and no direct involvement in the study. The research staff will report any 
unanticipated problems and adverse events to the PI and the independent monitor. The PI will 
be responsible that the study procedures follow the approved protocol.  
 
The independent monitor will receive a monthly safety report prepared by Dr. Dimitrova. The 
report will include information on any adverse events, unanticipated problems and protocol 

 
 
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deviations that have occurred each month. Reportable unanticipated adverse events include: 
infection at the acupuncture needling site, moderate-severe bruising and bleeding at the 
acupuncture site, moderate-severe pain and discomfort after acupuncture, new onset of 
weakness or numbness, permanent worsening of carpal tunnel syndrome symptoms and any 
other adverse events. Additionally, serious adverse events such as death, life-threatening 
adverse events, inpatient hospitalization, persistent or significant disability/incapacity will be 
immediately reported to Dr. Marburger and to the IRB. Unanticipated adverse events, as well as 
inability to tolerate experimental procedures will result in immediate exit from the study.      
 
Unanticipated problems will be reported in accordance with the OHSU procedures and 
timeframes - within 7 calendar days in case of death and life-threatening events or within 15 
calendar days for all other adverse events or unanticipated problems.  
8. INTERVENTION DISCONTINUATION  
A subject may withdraw consent at any point in the study, as stated in the OHSU Consent-and-
Authorization Form. Other reasons for exiting the study include inability to comply with QST 
due to a cognitive problem, inability to tolerate QST or NCS, inability to tolerate acupuncture or 
electroacupuncture.  
 
In general, since this is a brief study with only 2 visits, we do not anticipate that many subjects 
will exit the study. Should a subject exit the study, his/her data will be included in the analysis.  
9. STATISTICAL CONSIDERATIONS  
9.1. Sample Size Calculation 
A mechanistic study of acupuncture, which examines its local, nerve-specific effects using 
Quantitative Sensory Testing (QST) and Nerve Conduction Studies (NCS) as outcome measures 
has not been attempted before. Therefore, we estimated acupuncture’s effects based on larger 
studies drawn from the literature. Changes in acupuncture-associated sensation were derived 
from Lang et al (42) - an evaluation of manual and electroacupuncture- induced analgesia in the 
legs, using 24 healthy subjects, 12 men and 12 women, in a cross-over design. Effect sizes in 
Median nerve conduction velocity (NCV) were calculated as clinically relevant changes from the 
mean NCV reported by Kimura et. al (52) and Di Guglielmo et. al (53). Both studies were NCS 
characterizations specifically in CTS with 105 and 198 patients respectively and publicized in 
the AAEM summary statement on electrodiagnostic parameters in CTS (54). 
 
QST testing from the Lang et al (42) acupuncture intervention was observed to be a significant 
predictor of Cold Detection Threshold (CDT), with a 0.2°C change (-3.6 ± 0.9 °C to -3.4 ± 0.4 
°C) seen in the low-frequency-acupuncture treated legs. As this study was conducted in healthy 
subjects, we expect to see a greater effect of acupuncture on patients with neuropathy, especially 
as the acupuncture will be administered locally, with greater potential to affect the underlying 
nerve. Sample size estimation assumed the variance of the change in QST outcomes due to local 
acupuncture delivery over the Median and Ulnar nerves will be comparable to the variance in 
QST observed by Lang after acupuncture in healthy nerves (σ2CDT = 0.696 (°C)2).  Under these 
assumptions, a minimum QST change of 0.35°C, considered reasonable as an on-treatment effect 

 
 
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size in CDT, would be observed as statistically significant at a significance level of α=0.05 with 
80% power with 20 subjects per arm. 
 
 
The pooled parameters of the studies by Kimura et al (52) and Di Guglielmo et al (53) observed 
a mean Median nerve motor NCV of 47.5 ± 5.76 m/s in their combined cohort of 303 CTS 
patients. At minimum and assuming the same variance as seen historically (σ2NCV = 33.2 (m/s)2), 
an 8% change in NCS (corresponding to a clinically feasible 3.7 m/s change post-intervention) 
would be considered significant with the same arm size of 20 subjects and at the same 
significance of α=0.05 and 80% power. 
 
Although estimated from the literature, these on-treatment effect sizes are considered reasonable 
based on previously collected pilot data in three subjects.  When treatment and testing location 
were matched, a 0.337°C increase in CDT was observed in the Median nerve compared to the 
Ulnar nerve. Similarly, a Median nerve motor NCV improvement of 3.3 m/s was observed in the 
wrist. These initial pilot values are encouraging as they agree well with projected on-treatment 
effect size estimates from the literature.   
 
Specific Aim 1: We expect that the proposed sample size of 20 per acupuncture modality will 
enable us to see significant treatment-dependent changes in the NCS and QST (CDT, VDT) of 
the diseased Median nerve within each of the 3 intervention systems (MA, LF-EA, HF-EA).  
 
Specific Aim 2: For the current study, the Ulnar nerve is serving as a healthy control to allow for 
comparison to the diseased Median nerve post-intervention.  Historic studies measuring the local, 
direct effect of acupuncture on a healthy nerve or studies comparing the local effects of 
acupuncture on a healthy versus a diseased nerve are not available. With respect to our Specific 
Aim 2 hypothesis, the Ulnar nerve is serving as a disease-free control condition, wherein 
acupuncture-dependent change in QST and NCS in the Ulnar nerve is anticipated to be largely 
negligible as the nerve is already functioning at optimal physiologic parameters. Due to this 
expectation of negligible treatment effect in the Ulnar nerve, the proposed sample size from 
Specific Aim 1 (20 subjects per acupuncture modality) is expected to be sufficient for these 
comparisons within each type of acupuncture. Further, we plan to carry out the Median/Ulnar 
nerve comparisons separately for each of the 3 intervention modalities. The use of both Median 
and Ulnar nerves lets the treatment as well as control conditions of interest come from the same 
subjects, allowing them to serve as their own controls.  However, this repetition design warrants 
the use of mixed-model analysis so the random-effects portion can account for the intra-subject 
serial correlation expected with repeated measurements.   
 
Specific Aim 3: With regards to the proper sample size for comparison among the 3 types of 
acupuncture – we based the sample size calculation for each study arm in part on the effect sizes 
observed by Lang et al (42), who enrolled 24 healthy subjects in 6 groups involving a cross over 
between manual, low-frequency and high-frequency acupuncture and were able to observe 
significant differences in QST (CDT) between the 3 acupuncture modalities, p=0.0034. In our 
current study, the cross-over design is based on the comparisons of Median and Ulnar nerves; 
however, the individual methods of acupuncture will be populated by different cohorts.  For this 
reason, the random-effects blocking of our mixed- models will have the nerve dependence 

 
 
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grouped by subject but the modality contrasts will be inter-subject and not require a serial 
correlation correction. With a significant difference observed by Lang et al with groups of n=6, 
the proposed sample size of 20 per intervention group should be more than sufficient to observe 
differences among the modalities, even without the explicit cross-over design. Please see 
statistical analysis plan for further details.  
 
As the goal is to recruit 20 subjects per arm, for a total of 60 study completers, we anticipate the 
need to screen and enroll approximately 75 subjects, including with baseline nerve conduction 
studies to confirm the diagnosis of mild-moderate CTS and assure that the electrodiagnostic 
inclusion criteria for this study are met. 
 
9.2. Stratified Randomization – See section 4.4 
9.3. Outcome Measures and Statistical Hypotheses, as outlined in the Specific Aims  
Specific Aim 1: Characterize the effects of acupuncture on QST (cold and vibration sensation 
thresholds) and nerve conduction parameters in the Median and Ulnar nerves.  
Hypothesis: Acupuncture will cause decrease in cold and vibration detection thresholds (improve 
sensation) in the underlying nerve sensory distribution only. Acupuncture will cause NCS changes, 
characteristic of improved nerve function. 
The outcomes generated in this aim will be the baseline and post-acupuncture values of CDT and 
VDT from Week 1 and Week 2, as well as baseline and post-acupuncture nerve conduction study 
data from both weeks, consisting of: distal motor/sensory latencies, CMAP and SNAP amplitudes, 
CMAP area and duration, nerve conduction velocities.  
 
Specific Aim 2: Compare the effects of acupuncture on a diseased nerve (Median) to those of a 
healthy nerve (Ulnar), using QST (cold and vibration sensation thresholds) and NCS 
parameters.  
Hypothesis: There will be greater change in cold and vibration detection thresholds and NCS 
parameters in the median nerve compared to the ulnar, due to the lower functional baseline of the 
median nerve. 
The outcomes generated in this aim consist of statistical comparison of acupuncture-induced CDT, 
VDT and NCS changes in the Median nerve to those in the Ulnar nerve. The Post- minus Pre- 
acupuncture differences will be compared for the Median and Ulnar nerves in pooled data from all 3 
groups, using independent sample t-testing.  
 
Specific Aim 3: Compare the effects of manual acupuncture to those of low-frequency and 
high-frequency electroacupuncture.  
Hypothesis: High-frequency electroacupuncture will have greater effect on NCS, QST followed by 
low-frequency electroacupuncture and manual acupuncture, in accordance to traditional practices. 
Acupuncture-induced changes in CDT, DVT and NCS parameters will be compared among the 3 
groups (Post- minus Pre- changes), using ANOVA. 
 
9.4. Statistical Analysis Plan  
Primary statistical analysis for all 3 Specific Aims will use linear mixed-effect models to 
evaluate the effects of treatment group and intervened nerve location on the outcome measures 
described above. A mixed-model design will be used to create an intention-to-treat framework 

 
 
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and allow for any missing data. Principal assessment will be on the change in outcomes resulting 
from acupuncture intervention, calculated as the difference in outcomes before and after 
treatment. These outcomes will include CDT and VDT, distal motor/sensory latencies, CMAP 
and SNAP amplitudes, CMAP area and duration, nerve conduction velocities (Specific Aim1). 
Acupuncture characterization will be carried out first in the Median and Ulnar nerves of the arm 
(Specific Aims 1, 2). In both Median and Ulnar nerve interventions, group will be a three level 
factor based on the type of acupuncture - MA, LF-EA and HF-EA (Specific Aim 3). 
 
Specific Aims 1 and 2: 
As a principal independent variable, location of the intervention will be a four-level factor 
encompassing the possible combinations of treated and evaluated nerves. For Specific Aims 1 
and 2, these levels will be: MM – Median treated and tested, MU – Median treated and Ulnar 
tested, UM – Ulnar treated and Median tested, and UU – Ulnar treated and tested. A time 
variable (Week 1, Week 2) will also be included to test for any effects due to order of the treated 
nerves. Additional covariates known to be associated with QST and NCS outcomes such as age 
and gender will be corrected for as well. Secondary analysis will include treatment evaluations of 
outcomes within each location of intervention and additional contrasts between the four time 
points (pre and post treatment for both Week 1 and Week 2). Persistence of the acupuncture 
effects will specifically be assessed by comparing changes in outcomes after the first treatment 
but before the second session.  
 
Another way to characterize the wash-out effect of acupuncture is to compare baseline data from 
Week 1 and Week 2. We will perform an exploratory analysis to assess for an interaction 
between location and time, in a mixed linear model. We will incorporate nerve location, 
evaluation time and the location-time interaction to check for dependencies between Week 1 and 
Week 2. As stated, the dependent outcomes of all models are the change in QST and NCS from 
baseline to post-acupuncture.  This will allow for a full assessment of washout and carry-over 
effects with respect both to the nerve location (healthy Ulnar vs diseased Median), time (Week 1 
vs Week 2) as well as the order of nerve assessment (the interaction).  However, with the 
repeated nerve measures, it will still be necessary to utilize a mixed-model approach so that the 
random-effects blocking (nerve location dependent on subject) will allow for the intra-subject 
serial correlation. For the final model, although exploration of the wash-out effect will be 
critical, it will pose to be impractical to keep all these covariates in the final model. Only 
significant time-dependent interactions will be included since the model would otherwise suffer 
from overfitting due to too many covariates and the limited sample size.  
 
Specific Aim 2: Following completion of Specific Aim 1, we expect to see significant 
acupuncture effect on the Median nerve (within each acupuncture group). In our proposed mixed 
linear model for Specific Aims 1 and 2 this would represent MM on the level of each individual 
group (MA, LF-EA, HF-EA). Conversely, we do not expect to observe a significant effect of 
acupuncture on the healthy Ulnar nerve as it is already functioning at optimal physiologic level. 
This would be the UU at the level of each individual group and corresponds to a clinical control. 
We will conduct direct contrasts between MM and UU as part of the mixed linear model with 
nerve location, time dependencies and random-effects grouping following the same design as in 
Specific Aim 1.  
 

 
 
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Specific Aim 3: We will revise the linear mixed model and focus on the MM factor from 
Specific Aims 1 and 2 (Median nerve treated and tested). In this revised model we will 
incorporate acupuncture modality as a 3-factor covariate (MA, LF-EA, HF-EA). Incorporating 
both the 4-factor sets of nerve intervention/assessment combinations and the 3-factor 
acupuncture modality would create a very complex model with over 15 variables. As described 
in the washout analysis, this will lead to overfitting of the model and cause it to be underpowered 
at 60 subjects. We could run a similar revised mixed liner model analysis substituting UU, UM 
or MU for MM, although this would be beyond the scope of Specific Aim 3.   
 
Because of the exploratory nature of our analyses, no adjustment for multiple testing will be 
undertaken. Raw P values 0.05 will be regarded as statistically significant. Regardless, the 
multiple assessments inherent in the exploratory analysis will be discussed in future publications. 
Statistical analysis will be performed using SAS 9.1 (SAS Institute, Cary, NC). 
 
9.5. Interim Analyses and Stopping Rules 
There are no plans to conduct any interim analyses of primary and secondary outcome data prior 
to study completion. Manuscript and abstract presentations will focus on methodological and 
descriptive aspects of the study. No final data and safety monitoring plan has been discussed in 
detail and approved by NCCIH. In the event that such a plan involves a DSMB we propose an 
adverse event listing report rather than an interim analysis.  
Similarly, we do not plan to conduct any futility analyses prior to termination of the study. As 
this is not a treatment study, but a brief 2-session based mechanistic study futility in the sense of 
lack of symptomatic improvement of CTS does not carry the same implications because the 
study consists of 2 visits which are aimed to measure an immediate nerve-specific, local 
physiologic response, whereas a treatment protocol for CTS typically involves 2 sessions per 
week over a period of 6-8 weeks and needling of additional acupuncture points than the ones 
tested in this study.  
10. DATA COLLECTION AND QUALITY ASSURANCE 
10.1. Data Collection Forms and Participant Confidentiality 
The research material obtained from all subjects consists of relevant medical history information 
as part of the screening process, physiologic data such as nerve conduction parameters and 
sensory threshold values. No research personnel will have access to individually identifiable 
private information about human subject. Privacy and anonymity will be assured by replacing 
names and other identifying information with encoded identifiers, with the encoding key kept in 
a separate secure location. The PI will fill out the Study Screening Form (Appendix A) during 
screening in the EMG lab or in Neuromuscular clinic. For subject confidentiality, from the time 
of screening, only a 5-letter name code will be used to identify the subject. No study forms 
(beside the consent form) will contain a subject’s name. A key to 5-letter codes and subject 
identities will be kept in a password protected document on OHSU’s database, which requires 
network and workstation login. All methods to maintain subject confidentiality will adhere to 
HIPAA standards. HIPAA Authorization is part of the study consenting process.  
 

 
 
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All stored electronic data will be kept in password-protected documents, on computers protected 
by OHSU network password. Paper data will be stored in a locked secure cabinet, away from 
public access. Data storage will be compliant with all HIPAA and OHSU IRB regulations. All 
research materials will be used for research purposes only.  
 
Experimental data from Week 1 and Week 2 will be recorded by a blinded investigator – Tabatha 
Memmott, using the study Data Form (Appendix A). As Ms Memmott will be blinded to the 
intervention, the acupuncture data – acupuncture points used and modality (MA, LF-EA or HF-
EA) will be filled out by the acupuncturist at the end of the study session.  
 
10.2. Data Management  
This is a small pilot mechanistic study involving a sample size of 60 subjects. We will not be 
needing a data management organization or coordinating center. Data entry will be performed by 
Diana Dimitrova or a trained volunteer, who will not be involved in outcome measure 
assessment in any other way. They will use the data recorded in the Data Form (Appendix A). 
Data will be stored in a password-protected Excel spreadsheet. Once a subject completes the 
study, the PI will verify that the Data Form contents are entered correctly as PI will bear ultimate 
responsibility for data. This Excel spreadsheet be used by the statistician Charles Murchison, MS 
to conduct study data analysis as outlined above.  
 
10.3. Quality Assurance and Training 
All study staff are trained in Protection of Human Subjects, Responsible Conduct of Research 
and Conflict of Interest as mandated by OHSU’s IRB. Staff will be familiar with this study 
protocol and trained in study procedures in lab practice sessions.  
 
Over the past 1.5 years we have achieved lab consistency and reproducibility and have 
successfully performed the protocol on 3 pilot subjects. Dr. Dimitrova has undergone training in 
NCS and QST under the direction of Dr. Jau-Shin Lou, MD, PhD, who was director of the EMG 
lab during Dr. Dimitrova’s fellowship.  
 
10.4. Protocol Deviations 
Protocol deviations will be reported to Dr. Dimitrova and recorded. When appropriate, these will 
be reported to OHSU’s IRB and included in DSMP.  
 
10.5. Monitoring 
Study monitoring will be performed by NCCIH, who will have access to all study records upon 
request.  
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY  
Subjects can withdraw consent from the study at any point, as outlined in the OHSU Consent-
and-Authorization Form (Appendix A).  
 
11.1. Institutional Review Board (IRB) Review  
This study will be overseen by OHSU’s IRB and run in concordance with all IRB regulations 
and procedures including but not limited to informed consent, HIPAA release authorization, 

 
 
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protection of human subject, responsible conduct of research,  conflict of interest and adverse 
event documentation, reporting and monitoring.  
11.2. Informed Consent Forms – see Appendix A and section 4.3 
11.3. Inclusion of Women and minorities 
Both genders and all ethnicities are included in the study. All minorities are included in our 
recruitment pools. We anticipate that the ethnic distribution of the study will reflect that of 
OHSU’s clinic population, which is a reflection of the population of Oregon and Southern 
Washington. So far 2 out of our 3 pilot subjects have been women and 1 of the 3 was Hispanic.  
 
Children will be excluded from the study as Carpal Tunnel Syndrome is exceedingly rare in the 
pediatric population and children under a certain age cannot sustain attention and focus to be 
reliable QST reporters.  
 
Patients without English proficiency will also be excluded from the study as QST reporting is a 
timed test, thus making translation impossible.  
11.4. Participant Confidentiality – see 10.1 
11.5. Study Discontinuation  
This study may be discontinued at any time by the IRB, the NCCIH, the OHRP, the FDA, or 
other government agencies as part of their duties to ensure that research participants are 
protected.  
12. PUBLICATION OF RESEARCH FINDINGS  
Any presentation, abstract, or manuscript generated from this study will be made available for 
review by NCCIH prior to submission. Additionally, NCCAM and Dr. Dimitrova’s K23 grant 
will be acknowledged in all publications.  
 
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3. NIH Consensus Conference. Acupuncture. JAMA. 1998 Nov 4;280(17):1518-24. 
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Electrother Res. 1984;9(2):79-106. 
19. Cheng KJ. Neuroanatomical basis of acupuncture treatment for some common illnesses. Acupunct 
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20. Cheng KJ. Neuroanatomical characteristics of acupuncture points: relationship between their 
anatomical locations and traditional clinical indications. Acupunct Med. 2011 Dec;29(4):289-94. 
21. Yang CP. A randomized clinical trial of acupuncture versus oral steroids for carpal tunnel syndrome: 
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22. Branco K, Naeser MA. Carpal tunnel syndrome: clinical outcome after low-level laser acupuncture, 
microamps transcutaneous electrical nerve stimulation, and other alternative therapies--an open 
protocol study. J Altern Complement Med. 1999 Feb;5(1):5-26. 
23. Naeser MA, Hahn KA, Lieberman BE, Branco KF. Carpal tunnel syndrome pain treated with low-
level laser and microamperes transcutaneous electric nerve stimulation: A controlled study. Arch 
Phys Med Rehabil. 2002 Jul;83(7):978-88. 
24. Banner R, Hudson EW. Case report: acupuncture for carpal tunnel syndrome. Ultrasound assessment 
of adjunct therapy. Can Fam Physician. 2001 Mar;47:547-9. 
25. Napadow V, Kettner N, Liu J, Li M, Kwong KK, Vangel M, Makris N, Audette J, Hui KK. 
Hypothalamus and amygdala response to acupuncture stimuli in Carpal Tunnel Syndrome. Pain. 2007 
Aug;130(3):254-66.  
26. Joo Oh H, Ko YK, Cho SS, Yoon SP. A cadaveric study of needle insertion at PC6 in eight wrists of 
four subjects and an understanding of the anatomy. Acupunct Med. 2012 Mar;30(1):44-6. 
27. Streitberger K, Eichenberger U, Schneider A, Witte S, Greher M. Ultrasound measurements of the 
distance between acupuncture needle tip at P6 and the median nerve. J Altern Complement Med. 
2007 Jun;13(5):585-91. 
28. Kessler J, Streitberger K. Perforation of the median nerve with an acupuncture needle guided by 
ultrasound. Acupunct Med. 2008 Dec;26(4):231-3. 
29. Hui KK, Nixon EE, Vangel MG, Liu J, Marina O, Napadow V, Hodge SM, Rosen BR, Makris N, 
Kennedy DN. Characterization of the "deqi" response in acupuncture. BMC Complement Altern 
Med. 2007 Oct 31;7:33. 
30. Kou W, Gareus I, Bell JD, Goebel MU, Spahn G, Pacheco-López G, Bäcker M, Schedlowski M, 
Dobos GJ. Quantification of DeQi sensation by visual analog scales in healthy humans after 
immunostimulating acupuncture treatment. Am J Chin Med. 2007;35(5):753-65. 

 
 
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31. Langevin HM, Churchill DL, Fox JR, Badger GJ, Garra BS, Krag MH. Biomechanical response to 
acupuncture needling in humans. J Appl Physiol. 2001 Dec;91(6):2471-8. 
32. Stecco C, Gagey O, Belloni A, Pozzuoli A, Porzionato A, Macchi V, Aldegheri R, De Caro R, 
Delmas V. Anatomy of the deep fascia of the upper limb. Second part: study of innervation. 
Morphologie. 2007 Mar;91(292):38-43. 
33. Stevens JC (1997): AAEM minimonograph 26: the electrodiagnosis of carpal tunnel syndrome. 
American Association of Electrodiagnostic Medicine. Muscle Nerve 20:1477–1486 
34. You H, Simmons Z, Freivalds A, Kothari MJ, Naidu SH (1999): Relationships between clinical 
symptom severity scales and nerve conduction measures in carpal tunnel syndrome. Muscle Nerve 
22:497–501. 
35. Practice parameter: electrodiagnostic studies in ulnar neuropathy at the elbow. American Association 
of Electrodiagnostic Medicine, American Academy of Neurology, and American Academy of 
Physical Medicine and Rehabilitation. Neurology. 1999 Mar 10;52(4):688-90. 
36. Stevens JC, Smith BE, Weaver AL, Bosch EP, Deen HG Jr, Wilkens JA. Symptoms of 100 patients 
with electromyographically verified carpal tunnel syndrome. Muscle Nerve. 1999 Oct;22(10):1448-
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37. Beekman R, Van Der Plas JP, Uitdehaag BM, Schellens RL, Visser LH. Clinical, electrodiagnostic, 
and sonographic studies in ulnar neuropathy at the elbow. Muscle Nerve. 2004 Aug;30(2):202-8. 
38. Dyck PJ, Zimmerman IR, O'Brien PC, Ness A, Caskey PE, Karnes J, Bushek W. Introduction of 
automated systems to evaluate touch-pressure, vibration, and thermal cutaneous sensation in man. 
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39. O’Brien, PC; Dyck, PJ; Kosanke, JL.”A computer evaluation of quantitative algorithms for 
measuring detection thresholds of cutaneous sensation.” In Quantification of Neurologic Deficit, 
Munsat, TL (ed.). Butterworths, Boston, MA: chapter 16: 197–206. 
40. “The Rochester Diabetic Neuropathy Study: Design, criteria for types of neuropathy, selection bias, 
and reproducibility of neuropathic tests.” Dyck, PJ; Kratz, KM; Lehman, KA; Karnes, JL; Melton III, 
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Zimmerman, IR. Neurology, 41 (1991): 799–807. 
41. Dyck PJ, O'Brien PC, Kosanke JL, Gillen DA, Karnes JL. A 4, 2, and 1 stepping algorithm for quick 
and accurate estimation of cutaneous sensation threshold. Neurology. 1993 Aug;43(8):1508-12. 
42. Lang PM, Stoer J, Schober GM, Audette JF, Irnich D. Bilateral acupuncture analgesia observed by 
quantitative sensory testing in healthy volunteers. Anesth Analg. 2010 May 1;110(5):1448-56. Epub 
2010 Mar 17. 
43. Aung, SKH, Chen, WPD. Clinical introduction to medical acupuncture.  Thieme Medical Publishers, 
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44. Manheimer E, White A, Berman B, Forys K, Ernst E. Meta-analysis: acupuncture for low back pain. 
Ann Intern Med. 2005 Apr 19;142(8):651-63.  
45. Furlan AD, van Tulder M, Cherkin D, Tsukayama H, Lao L, Koes B, Berman B. Acupuncture and 
dry-needling for low back pain: an updated systematic review within the framework of the cochrane 
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46. Linde K, Allais G, Brinkhaus B, Manheimer E, Vickers A, White AR. Acupuncture for migraine 
prophylaxis. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD001218.  
47. Linde K, Allais G, Brinkhaus B, Manheimer E, Vickers A, White AR. Acupuncture for tension-type 
headache. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD007587.  
48. Ezzo J, Richardson MA, Vickers A, et al. Acupuncture-point stimulation for chemotherapy-induced 
nausea or vomiting. Cochrane Database Syst Rev; 2006, Issue 2:CD002285.  
49. Kimura, J. Electrodiagnosis in Diseases of Nerve and Muscle: Principles and Practice. Oxford 
University Press, USA; 3rd edition (February 15, 2001). 
50. Langevin HM, Stevens-Tuttle D, Fox JR, Badger GJ, Bouffard NA, Krag MH, Wu J, Henry SM. 
Ultrasound evidence of altered lumbar connective tissue structure in human subjects with chronic low 
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51. Langevin HM, Sherman KJ. Pathophysiological model for chronic low back pain integrating 
connective tissue and nervous system mechanisms. Med Hypotheses. 2007;68(1):74-80. 
52. Kimura J. The carpal tunnel syndrome: Localization of conduction abnormalities within the distal 
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53. Di Guglielmo G, Torrieri F, Repaci M, Uncini A. Conduction block and segmental velocities in 
carpal tunnel syndrome. Electroencephalogr Clin Neurophysiol 1997;105:321-327. 
54. American Association of Electrodiagnostic Medicine, American Academy of Neurology, American 
Academy of Physical Medicine and Rehabiliation. Practice parameter for electrodiagnostic studies in 
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55. Amato AA, Russell JA. Neuromuscular disorders. New York: McGraw-Hill Medical, 2008 
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14. APPENDIX A – Study Forms 
 
CONTENTS: 
Subject Screening Form – pg. 37-39 
 
Lay Language Protocol Summary – pg.40-41 
 
OHSU Consent and Authorization Forms:  
Clinical Research Consent Summary – pg. 42-43 
Clinical Research Consent Form – pg. 44-48 
HIPAA Clinical Research Authorization – pg. 49-50 
 
Data Form 51-53 
 
 

SUBJECT 5- LETTER CODE   ___  ___  ___  ___  ___      DATE___________________ 
 
 
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1 
 
 
 
 
 
                
Local Effects of Acupuncture and Nerve Conduction Studies 
SUBECT SCREENING FORM 
 
 
EMG Criteria: NEUROMUSCULAR DIVISION ONLY 
 
INCLUSION CRITERIA: 
☐Mild-moderate CTS - NCS within 2 years AND one of the following: 
☐ Prolonged Median distal sensory AND/OR motor latency  
☐ Reduced Median SNAP amplitude ≥ 50% 
☐ Median CMAP amplitude (from APB)  > 50% of normal  
 
☐ CTS symptoms for at least 3 months  
 
☐ Age 18-75 
EXCLUSION CRITERIA: 
☐ Isolated Median Motor neuropathy  
☐ Absence of sensory neuropathy on NCS AND 
☐ Absence of sensory symptoms 
 
☐ Severe Carpal Tunnel Syndrome: 
☐ Absent SNAP recorded from the second digit AND/OR 
☐ CMAP amplitude from APB < 50% of normal (< 2.5 mv) 
 
☐ Martin-Gruber anastomosis  
 
☐  Ulnar neuropathy (ipsilateral to CTS) 
 
☐  Severe neuropathy symptoms – unable to tolerate acupuncture or QST 
☐  CTS release surgery 
☐  Other surgery on the arm or shoulder 
☐  Change in opioid, benzodiazepines, SSRIs or other sedating medications in the past 2       
months 
 
 
 
 
 
 

SUBJECT 5- LETTER CODE   ___  ___  ___  ___  ___      DATE___________________ 
 
 
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2 
 
 
 
 
 
                
 
SUBJECT SCREENING FORM 
 
Please list your current medications and the doses (if you know them): 
 
 
 
 
 
 
 
 
 
 
EXCLUSION CRITERIA 
 
Check if you have any of the following medical problems/conditions: 
 
☐ Wrist or elbow fracture, past arm trauma, loss of fingers, scarring  
☐  Alzheimer’s disease or other Mental Disability 
☐  Epilepsy 
☐  Other condition affecting sensation such as past stroke, Multiple Sclerosis or spinal cord 
disorder (Please specify) ___________________________________________________ 
☐  Cardiac Pacemaker 
☐  Hospitalization for anxiety or depression in the past 3 months 
☐  Other psychiatric condition you are being treated for (Please specify) 
____________________________________________________________________ 
☐  Bleeding/Clotting condition 
☐  Pregnancy  

SUBJECT 5- LETTER CODE   ___  ___  ___  ___  ___      DATE___________________ 
 
 
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3 
 
 
 
 
 
                
☐  Arthritis affecting the hands and fingers 
☐  Thyroid problems 
☐  Past chemotherapy treatment 
☐  Use of any experimental medications within the past 6 months 
☐  Any skin condition in the arm (dermatitis, bruises, weeping skin, skin lesions, infected skin, 
or necrotic skin) 
 
☐  Have you had a change in your medications in the past 2 months?  
 
☐  Yes – Please list specify below  
☐  No (skip to next question) 
  _____________________________________________________________ 
  _____________________________________________________________ 
  _____________________________________________________________ 
  _____________________________________________________________ 
 
☐  Have you used any illicit drugs, including marijuana in the past month  
(Response will be strictly confidential)              ☐  Yes 
 
☐  No 
 
☐  List how many (if any) drinks of alcohol you consume per week. List “0” if less than 1 per 
week.  
 
_________  (Number) of drinks per week 
 
 
 
 
 
 

 
 
Local Effects of Acupuncture in CTS, version 1 
 
 
 
1 
 
 
 
 
 
                
 
Principal Investigator: Alexandra Dimitrova, MD 
IRB#: 00008949 
Study/Protocol Title: 
Local Effects of Acupuncture on the Median and Ulnar Nerves in 
Patients with Carpal Tunnel Syndrome 
 
 
1. The purpose of this study is to measure the effects of acupuncture on 2 of the large 
peripheral nerves in the forearm. It will yield data, which may improve our understanding of 
how acupuncture works. 
 
2. We plan to recruit subjects with a diagnosis of Carpal Tunnel Syndrome from patients in 
the EMG lab and from the Neuromuscular clinic at OHSU. 
 
3. The purpose of this study is to learn more about the way acupuncture works. Our goal is to 
apply acupuncture in traditionally used points in the forearm close to the Median Nerve 
and Ulnar Nerve. We will measure the effect of acupuncture on those nerves, using Nerve 
Conduction Studies. Nerve Conduction Studies are a non-invasive test, consisting of small 
electrical stimuli applied to the arm. In clinical practice Nerve Conduction Studies are the 
gold standard for diagnosing Carpal Tunnel Syndrome.  No EMG (needle muscle testing) 
will be used in this research protocol.  
 
As another measurement of nerve function, we will use Quantitative Sensory Testing – a 
precise and non-invasive neurologic assessment of a subject’s ability to sense vibration 
and cold temperature in the hand.  
 
Week 1: 
The first week’s protocol will begin with Nerve Conduction Study and Quantitative Sensory 
Testing.  
 
Nerve Conduction Studies are the non-invasive part (with small electric stimulation, but no 
needles) of a larger test called EMG (electromyography). They consist of delivering small 
electrical stimuli over peripheral nerves and measuring the speed and magnitude of nerve 
conduction, so the health of the large peripheral nerves can be examined. Nerve 
Conduction Studies will be performed on the arm diagnosed with Carpal Tunnel 
Syndrome.  
 
Quantitative Sensory Testing is a non-invasive precise measurement of a person’s ability 
to perceive cold and vibration, tested over a small patch of skin on the hand. 
 
Those subjects whose Nerve Conduction Studies and Quantitative Sensory Testing meet 
the study’s criteria will proceed to acupuncture followed by repeat Nerve Conduction Study 
and Quantitative Sensory Testing.  
Lay Language Protocol Summary 
 
Research Integrity Office  
Mail code L106-RI 
3181 S.W. Sam Jackson Park Road 
Portland, Oregon 97239-3098 
tel: 503 494-7887 |  fax: 503 346-6808 

 
 
Local Effects of Acupuncture in CTS, version 1 
 
 
 
2 
 
 
 
 
 
                
 
Study participants will be randomly assigned to 3 groups - manual acupuncture group, 
low-frequency electroacupuncture group or high-frequency electroacupuncture group.  
 
Acupuncture consists of the insertion of thin, sterile, single-use disposable needles in the 
body. Various sensations are experienced during treatment including a distended feeling 
around the needle site, itching, tingling, a dull ache, burning or heaviness. There is minor 
discomfort during needle insertion and manipulation. During electroacupuncture 2 
acupuncture needles are connected to an electrostimulation machine and thus deliver a 
very small level electrical current to the tissues. The sensation of electroacupuncture are 
similar to the ones described above, but may also include painless muscle twitching. 
 
The first visit is expected to last 1:30-2:30 hours, depending on a subject’s ability to focus 
and sustain attention during the Quantitative Sensory Testing.  
 
Week 2: 
During the second week acupuncture (the same type as Week 1) will be applied to a 
different location in the forearm, again followed by Nerve Conduction Studies and 
Quantitative Sensory Testing.  
 
This session will last 1-2 hours. At the end of the second visit the study will be complete 
and subjects will be compensated for your time and effort. 
 
4. A 3-page screening form of inclusion/exclusion criteria will be used on enrollment in the 
study, which will ask questions about past and current medical conditions and 
medications.  
 
5. All subject identifying information will be removed from the test results. Data from multiple 
subjects will be combined and analyzed together in order to assess the combined effect of 
acupuncture on the Median Nerve and the Ulnar Nerve. We will be testing for differences 
among the manual acupuncture, low-frequency electroacupuncture and high-frequency 
electroacupuncture groups in the data analysis. The testing results will not be used to 
guide clinical decisions about patient care.  
 
 

 
Revised 6/28/2012 – Corrected 7/10/2012 
 
 
 
 
Page 1 of 2    
Scan to CO1450 
 
 
 
IRB#: __________ 
Protocol Approval Date: _____________ 
 
 
MED. REC. NO. _____ 
NAME 
_____ 
BIRTHDATE 
_____ 
 
 
 
Clinical Research Consent Summary 
 
Local Effects of Acupuncture on the Median and Ulnar Nerves in Patients with Carpal 
Tunnel Syndrome  
 
You are being asked to join a research study because you have been diagnosed with Carpal 
Tunnel Syndrome – a condition affecting the median Nerve in the wrist and causing symptoms 
such as painful burning, tingling, numbness and sometimes weakness in the hand. You do not 
have to join the study.  Even if you decide to join now, you can change your mind later. 
 
If you decide to join, you will be asked to sign a consent form, which shows you give permission 
to be in the study, and an authorization form, which shows you give permission for us to use 
your health information for the study. 
 
1. The purpose of this study is to learn more about acupuncture and its direct effects on the 
peripheral nerves. 
 
2. In this study, we will learn how acupuncture needles affect 2 peripheral nerves in the 
arm – the median Nerve and the ulnar Nerve. We want to learn: 
 
a. Whether acupuncture needles placed in traditionally used acupuncture points 
have any direct effect on the nearly nerves.  
 
b. We will test the nerve’s function by nerve conduction studies and quantitative 
sensory testing. Both of these are non-invasive tests and are generally 
considered safe.  
 
c. Acupuncture consists of the insertion of thin, sterile, single-use disposable 
needles in the body. Various sensations are experienced during treatment 
including a distended feeling around the needle site, itching, tingling, a dull ache, 
burning or heaviness. There is minor discomfort during needle insertion and 
manipulation. During electroacupuncture 2 acupuncture needles are connected 
to an electrostimulation machine and thus deliver a very small level electrical 
current to the tissues. The sensation of electroacupuncture are similar to the 
ones described above, but may also include painless muscle twitching.  

 
 
Revised 6/28/2012 – Corrected 7/10/2012 
 
Page 2 of 2 
MED. REC. NO.:______________________ 
 
NAME:______________________ 
 
Epic CSN (if applicable):______________________ 
 
 
3. This study’s investigators are funded by the National Institutes of Health and by OHSU.  
 
4. We do not know whether acupuncture can help improve the function of the peripheral 
nerves or minimize your carpal tunnel syndrome symptoms. 
 
5. If you join the study, you will have 2 visits at OHSU, 1 week apart. The first visit should 
last 4-4.5 hours and the second – 3.5-4 hours. At the end of the second visit the study 
will be complete and you will be compensated for your time and effort.  
 
6. The risks involved in participating in this study are comparable to the general risks of 
receiving acupuncture, as described above.  
 
7. You may withdraw your consent voluntarily at any point of the study and choose to not 
undergo further testing.

 
Revised 6/28/2012 – Corrected 7/10/2012 
 
 
 
 
Page 1 of 5    
Scan to CO1450 
 
 
 
 
IRB#: __________ 
 
 
MED. REC. NO. _____ 
NAME 
_____ 
BIRTHDATE 
_____ 
 
 
Clinical Research Consent Form 
 
TITLE: Local Effects of Acupuncture on the Median and Ulnar Nerves in Patients with Carpal 
Tunnel Syndrome 
 
 
PRINCIPAL INVESTIGATOR: 
Alexandra Dimitrova, MD   (503) 494-0744 
 
SPONSOR:  NIH/NCCIH  
 
 
PURPOSE: You are being asked to join a research study because you have been diagnosed with 
Carpal Tunnel Syndrome – a condition affecting the Median Nerve in the wrist and causing 
symptoms such as painful burning, tingling, numbness and sometimes weakness in the hand. 
 
The purpose of this study is to learn more about the way acupuncture works. Our goal is to apply 
acupuncture in traditionally used points in the forearm close to the Median Nerve and Ulnar 
Nerve and measure the effect of acupuncture on those nerves, using Nerve Conduction Studies, 
which are identical to the test you underwent when you were diagnosed with Carpal Tunnel 
Syndrome (consisting of small electrical shocks to the arm). No EMG (needle muscle testing) 
will be used in this research protocol.  
 
As another measurement of nerve function, we will use Quantitative Sensory Testing – a precise 
neurologic assessment of your ability to sense vibration and cold temperature in the hand.  
 
This study attempts to measure the effects of acupuncture on 2 of the large peripheral nerves in 
the forearm. It will yield data, which may improve our understanding on how acupuncture 
works.  
 
While acupuncture has been shown to help certain patients with neuropathy, including Carpal 
Tunnel Syndrome, our experimental protocol is somewhat different from typically used 
acupuncture treatments for Carpal Tunnel Syndrome. It is possible that some of the study 
participants may feel improvement in their Carpal Tunnel Syndrome symptoms; specifically 
acupuncture may improve the speed and amplitude of nerve conduction and sensation in the 
hand. This would be an unintended benefit of the study and is by no means guaranteed. We do 
not know whether acupuncture applied to the forearm would affect the nerves favorably.  

 
 
Revised 6/28/2012 – Corrected 7/10/2012 
 
Page 2 of 5 
MED. REC. NO.:______________________ 
 
NAME:______________________ 
 
Epic CSN (if applicable):______________________ 
 
 
This study requires 2 visits to OHSU, 1 week apart. We plan to enroll a total of 60 subjects, who 
meet the inclusion/exclusion criteria. 
 
 
 
 
PROCEDURES:   
 
 
Week 1: 
The first week’s protocol will begin with Nerve Conduction Study and Quantitative Sensory 
Testing. You have undergone Nerve Conduction Studies as part of your diagnosis of Carpal 
Tunnel Syndrome. Our procedure will be somewhat shorter. Nerve Conduction Studies are the 
non-invasive part (with small electric stimulation, but no needles) of the test you underwent 
when you were diagnosed with Carpal Tunnel Syndrome. Quantitative Sensory Testing is a non-
invasive precise measurement of your ability to perceive cold and vibration, tested over a small 
patch of skin on the hand. 
 
If the results of these tests meet the study inclusion criteria, you will proceed to acupuncture 
followed by repeat Nerve Conduction Study and Quantitative Sensory Testing. You may be 
given manual acupuncture, low frequency or high frequency electroacupuncture, depending on 
the randomization process.  
 
The first visit should last 1:30-2:30 hours, depending on your ability to focus and sustain 
attention during the quantitative sensory testing.  
 
Week 2: 
During the second week acupuncture (the same type as Week 1) will be applied to a different 
location in the forearm, again followed by Nerve Conduction study and Quantitative Sensory 
Testing.  
 
This session will last 1-2 hours. At the end of the second visit the study will be complete and you 
will be compensated for your time and effort. 
 
This is a randomized study. Neither you nor the investigator can choose which modality of 
acupuncture group you will be assigned to – manual acupuncture, low frequency or high-
frequency electroacupuncture. 
 
Your medical record will be reviewed in order to obtain information needed for the study. Specifically, 
your nerve conduction studies/EMG and current medications will be reviewed, as well as a list of current 
and past medical conditions.  
 
 

 
 
Revised 6/28/2012 – Corrected 7/10/2012 
 
Page 3 of 5 
MED. REC. NO.:______________________ 
 
NAME:______________________ 
 
Epic CSN (if applicable):______________________ 
 
If you have any questions regarding this study now or in the future, contact Dr. Dimitrova at 
(503) 494-0744. You will not be contacted with results after completion of this study as clinical 
decisions will not be made on the basis of any of the study results, as this is a study about the 
mechanism of acupuncture, rather than its treatment effects. 
  
RISKS AND DISCOMFORTS:  
Acupuncture delivered by an experienced practitioner is quite safe, however has small risks. 
These include infection (rare), bruising and bleeding into the tissues (usually small and self-
limiting), pain and discomfort, weakness, tiredness, fainting, nausea, aggravation of existing 
symptoms for a short time. If at any time you experience a stinging, burning or any 
uncomfortable feeling please let the investigator know so the needle may be adjusted or 
removed. 
 
There are no known side effects to nerve conduction studies, aside from momentary discomfort 
during testing. This test is painless and the cold temperatures cannot damage the skin in any way. 
Quantitative Sensory Testing requires focused attention, but is comfortable and safe, without any 
known side effects. 
 
Confidentiality risks:  Efforts will be made to keep your personal information confidential as 
described in the CONFIDENTIALITY section, but we cannot guarantee total privacy.  There is a 
small chance that your information could be accidentally released. 
 
BENEFITS:  
You may or may not personally benefit from being in this study.  However, by serving as a 
subject, you may help us learn how to benefit patients in the future. 
 
ALTERNATIVES:  
You may choose not to be in this study. If you are interested in trying acupuncture as a patient, 
you may visit OHSU’s acupuncture clinic, within the Neurology department. 
 
CONFIDENTIALITY: 
We will not use your name or your identity for publication or publicity purposes. A code number 
will be assigned to you, as well as to information about you.  Only the investigators named on 
this consent form will be authorized to link the code number to you.  Other investigators who 
may be performing parts of the testing and data analysis will be given only the code number, 
which will not identify you. 
 
Research records may be reviewed and copied by people involved in conducting or overseeing 
research including the OHSU Institutional Review Board and the Office for Human Research 
Protections (OHRP). All other parties including employers, insurance companies, and relatives 
will be refused access to your information unless you provide written permission or unless we 
are required by law to release it. 
 
We may request your social security number in order to process any payments for participation. 

 
 
Revised 6/28/2012 – Corrected 7/10/2012 
 
Page 4 of 5 
MED. REC. NO.:______________________ 
 
NAME:______________________ 
 
Epic CSN (if applicable):______________________ 
 
 
COSTS AND COMPENSATION: There will be no cost to you or your insurance company to 
participate in this study.  
 
During Week 1, Baseline Nerve Conduction Study and Quantitative Sensory Testing will be 
obtained. If it is determined that you are not a candidate for the acupuncture session, you will 
exit the study and will be compensated $25 USD.  
 
If you are determined to be a candidate for the acupuncture sessions on Week 1 and Week 2, you 
will be compensated a total of $75 at the end of your Week 2 visit. If you need to exit the study 
prior to completion at any other point prior to completion during Week 1 or Week 2, you will be 
compensated a total of $25.  
 
LIABILITY:   
If you believe you have been injured or harmed while participating in this research and require 
immediate treatment, contact Dr. Dimitrova at (503) 494-0744. 
 
You have not waived your legal rights by signing this form. If you are harmed by the study 
procedures, you will be treated. Oregon Health & Science University does not offer to pay for 
the cost of the treatment. Any claim you make against Oregon Health & Science University may 
be limited by the Oregon Tort Claims Act (ORS 30.260 through 30.300). If you have questions 
on this subject, please call the OHSU Research Integrity Office at (503) 494-7887.  
 
PARTICIPATION: 
If you have any questions regarding your rights as a research subject, you may contact the OHSU 
Research Integrity Office at (503) 494-7887.   
 
You do not have to join this or any research study.  If you do join, and later change your mind, 
you may quit at any time.  If you refuse to join or withdraw early from the study, there will be no 
penalty or loss of any benefits to which you are otherwise entitled. 
 
You may be excluded from further participation in the study if  after the initial testing on Week 1 
your results do not meet the study criteria for acupuncture and/or if you are unable to participate 
in the Quantitative Sensory Testing.  
 
 
SIGNATURES: 
Your signature below indicates that you have read this entire form and that you agree to be in 
this study.   
 
We will give you a copy of this form. 
 
 

 
 
Revised 6/28/2012 – Corrected 7/10/2012 
 
Page 5 of 5 
MED. REC. NO.:______________________ 
 
NAME:______________________ 
 
Epic CSN (if applicable):______________________ 
 
___________________________________ 
Name of Subject, Printed 
 
 
 
Signature of Subject  
 
 
 
 
Date 
 
 
___________________________________ 
Name of Person Obtaining Consent, Printed 
 
 
 
Signature of Person Obtaining Consent 
 
 
Date 

 
Revised 6/28/2012 – Corrected 7/10/2012 
 
 
 
 
Page 1 of 2    
Scan to CO1450 
 
 
 
IRB#: __________ 
 
 
MED. REC. NO. _____ 
NAME 
_____ 
BIRTHDATE 
_____ 
 
 
HIPAA CLINICAL RESEARCH AUTHORIZATION 
 
Title of Study: 
Local Effects of Acupuncture on the Median and Ulnar Nerves in 
Patients with Carpal Tunnel Syndrome 
Name of Principal Investigator: 
Alexandra Dimitrova, MD 
Phone Number: 
(503) 494-0744 
 
We have already asked you for your consent to be in the research study.  We are also required to 
seek separate permission to use your health information for the study.  The Health Insurance 
Portability and Accountability Act (HIPAA) is a federal law designed to help protect the privacy 
of health information. 
 
During this study, OHSU will use and disclose (release) health information about you.  Under 
federal law, we may not use or disclose it unless you authorize us to do so by signing this form.  
This authorization is voluntary.  You do not have to sign this form.   If you choose not to sign it, 
you cannot join this study. 
 
The health information we will collect, use, and disclose is described in the attached consent 
form.  The consent form also describes why we will use the health information.  Investigators, 
study staff, and others at OHSU who are involved in the research or overseeing the research may 
use and disclose your health information. 
 
We may send your health information to others outside OHSU who are involved in the research 
or overseeing the research, including: 
 
• The Office for Human Research Protections, which oversees research involving humans 
 
When we send information outside of OHSU, it may no longer be protected under federal law.  
In this case, your information could be used and re-released without your authorization. 
 
We may continue to use and disclose your health information indefinitely. 
 
You have the right to withdraw this authorization at any time. To withdraw your permission for 
us to use information that identifies you, please send a written request or email to: 
 
Alexandra Dimitrova, MD 
Mail Code: CR 120 

 
 
Revised 6/28/2012 – Corrected 7/10/2012 
 
Page 2 of 2 
MED. REC. NO.:______________________ 
 
NAME:______________________ 
 
Epic CSN (if applicable):______________________ 
 
3181 S.W. Sam Jackson Park Road 
Portland, OR 97239-3098 
Tel. (503) 494-0744 
e-mail: dimitroa@ohsu.edu 
 
The use and disclosure of your health information for this research will stop as of the date the 
principal investigator receives your request.  However, the use and disclosure of information 
collected in good faith before your request arrives will continue.  Withdrawing this authorization 
will not affect your health care or your relationship with OHSU. 
 
Please ask the investigator or study staff if you have any questions about this HIPAA 
authorization. 
 
We will give you a copy of this signed form.  
 
 
___________________________________ 
Name of Subject, Printed 
 
 
 
Signature of Subject  
 
 
 
 
Date 
 
 
 
 
 
___________________________________ 
Name of Person Obtaining Authorization, Printed 
 
 
 
 
Signature of Person Obtaining Authorization 
 
Date 
 

SUBJECT 5- LETTER CODE   ___  ___  ___  ___  ___      DATE___________________ 
 
__  WEEK 1    ___WEEK 2 
 
Page 1 
 
 
Local Effects of Acupuncture on the Median and Ulnar Nerves 
DATA FORM 
 
BASELINE  
 
 
 
 
 
Temperature_______________ 
 
COLD Detection Threshold 
 
MEDIAN 
 
 
ULNAR 
 
#1 ___________  
 
#1 ___________  
 
#2 ___________ 
 
#2 ___________  
 
#3 ___________ 
 
#3 ___________ 
 
Average ___________ 
Average ___________ 
 
 
VIBRATION Detection Threshold  
 
 
Temperature_______________ 
 
MEDIAN 
 
 
ULNAR 
 
#1 ___________  
 
#1 ___________  
 
#2 ___________ 
 
#2 ___________  
 
#3 ___________ 
 
#3 ___________ 
 
Average ___________ 
Average ___________ 
 
 
NERVE CONDUCTION STUDIES 
 
 
Temperature_______________ 
MEDIAN Motor 
Supramax CMAP Amplitude      WRIST __________ 
ELBOW___________ 
CMAP Area      WRIST __________ 
ELBOW___________ 
NCV_______ 
Distal Motor Latency      WRIST __________ 
ELBOW___________ 
Duration (Wrist) _____________  (Elbow) _____________ 
 
 
ULNAR Motor 
Supramax CMAP Amplitude      WRIST __________ 
ELBOW___________ 
CMAP Area      WRIST __________ 
ELBOW___________ 
NCV_______ 
Distal Motor Latency      WRIST __________ 
ELBOW___________ 

SUBJECT 5- LETTER CODE   ___  ___  ___  ___  ___      DATE___________________ 
 
__  WEEK 1    ___WEEK 2 
 
Page 2 
 
Duration (Wrist) _____________  (Elbow) _____________ 
 
MEDIAN Sensory 2nd Digit  
 
 
 
Temperature_______________ 
Supramax SNAP Amplitude ___________  
 
SNAP Area ________ 
NCV Wrist ________ 
Distal Sensory Latency      1) _______   2)  _______ 
 
ULNAR Sensory 5th Digit 
Supramax SNAP Amplitude ___________  
 
SNAP Area ________ 
NCV Wrist ________ 
Distal Sensory Latency     1) _______   2)  _______ 
 
ACUPUNCTURE SETTING 
START TIME________  Temperature_______________ 
ACUPUNCTURE POINTS ___________________ 
__ Manual 
__ Low-frequency 
__ High-frequency   
 
POST-ACUPUNCTURE MEASUREMENTS 
 
Temperature_______________ 
 
COLD Detection Threshold 
 
MEDIAN 
 
 
ULNAR 
 
#1 ___________  
 
#1 ___________  
 
#2 ___________ 
 
#2 ___________  
 
#3 ___________ 
 
#3 ___________ 
 
Average ___________ 
Average ___________ 
 
 
VIBRATION Detection Threshold  
 
 
Temperature_______________ 
 
MEDIAN 
 
 
ULNAR 
 
#1 ___________  
 
#1 ___________  
 
#2 ___________ 
 
#2 ___________  
 
#3 ___________ 
 
#3 ___________ 
 
Average ___________ 
Average ___________ 

SUBJECT 5- LETTER CODE   ___  ___  ___  ___  ___      DATE___________________ 
 
__  WEEK 1    ___WEEK 2 
 
Page 3 
 
 
 
NERVE CONDUCTION STUDIES 
 
 
Temperature_______________ 
MEDIAN Motor 
Supramax CMAP Amplitude      WRIST __________ 
ELBOW___________ 
CMAP Area      WRIST __________ 
ELBOW___________ 
NCV_______ 
Distal Motor Latency      WRIST __________ 
ELBOW___________ 
Duration (Wrist) _____________  (Elbow) _____________ 
 
 
 
ULNAR Motor 
Supramax CMAP Amplitude      WRIST __________ 
ELBOW___________ 
CMAP Area      WRIST __________ 
ELBOW___________ 
NCV_______ 
Distal Motor Latency      WRIST __________ 
ELBOW___________ 
Duration (Wrist) _____________  (Elbow) _____________ 
 
Median Sensory 2nd Digit 
 
 
 
 
Temperature_______________ 
Supramax SNAP Amplitude ___________  
 
SNAP Area ________ 
NCV Wrist ________ 
Distal Sensory Latency      1) _______   2)  _______ 
 
Ulnar Sensory 5th Digit 
Supramax SNAP Amplitude ___________  
 
SNAP Area ________ 
NCV Wrist ________ 
Distal Sensory Latency     1) _______   2)  _______