Acupuncture for PTSD in Combat Veterans
Phase: NA
Conditions: Posttraumatic Stress Disorder
Sponsor: VA Office of Research and Development

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Acupuncture for Combat PTSD: A Clinical Trial 
Protocol 
NCT ID: CLNA-02-15F 
Date: February 1, 2017 
Date Revised: April 20, 2018 
 
 

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I. Background 
The Significance of PTSD and its Psychiatric Comorbidities in the Study Population 
Posttraumatic Stress Disorder (PTSD) is a debilitating disorder characterized by re-experiencing aspects of the 
original trauma, avoidance and numbing of trauma reminders, negative alterations in cognition and mood, and 
hyperarousal (APA, 2013). Lifetime prevalence of PTSD in community samples is about 6.8% (Kessler et al, 
2005) and as high as 30% in Vietnam Veterans (Kulka et al, 1988) and rape survivors (Resnick et al, 1993). 
Recent OEF/OIF/OND Veterans have 13-16% PTSD prevalence, dependent on combat exposure (Litz et al, 
2009). Personnel were at high risk for severe injury and for witnessing or suffering from the aftermath of 
violence (Ricks, 2004). Of soldiers in Iraq, 86% reported knowing someone who was seriously injured or killed, 
68% saw dead or seriously injured Americans, and 51% handled human remains (Hoge et al, 2004). Active and 
reserve soldiers report similar rates of combat experiences (67% vs. 70%) (Milliken et al, 2007). 
PTSD is highly comorbid (83-90%) with other psychiatric disorders, including mood, substance use, personality 
disorders, depression, and panic disorder (Bradley et al, 2005). Approximately 50 to 60% of PTSD patients 
have major depressive disorder (Bradley et al, 2005). This clinical comorbidity parallels shared biology. 
Neurological mechanisms of PTSD, depression, and anxiety disorders have many similarities (Rechlin et al, 
1995). The known genetic variance for depression and anxiety disorders accounts for the majority of known 
genetic variance for PTSD (Koenen, 2007). Because of the high clinical and biological comorbidity, choosing 
the most appropriate inclusion and exclusion criteria for the proposed study is challenging. Excluding potential 
subjects with comorbidity markedly reduces feasibility and generalizability. For these reasons, most clinical 
studies limit exclusion of comorbidities (e.g., (Schnurr et al, 2003). Selection criteria are meant to recruit a 
sample with chronic PTSD and common comorbidities, yet without severe depression or other comorbid 
conditions that would likely confound treatment and biological assessment. 
Interventions for PTSD 
Evidence Based Pharmacotherapy and Psychotherapy. A recent review noted strengths and limitations of 
interventions that have evidence of efficacy for PTSD; references for this are in the publication in Appendix 3 
(Hollifield, 2011). Ipser and colleagues published a recent review and meta-analysis of medication RCT’s (Ipser 
et al, 2012). The meta-analysis included 23 trials that met investigators inclusion criteria (direct placebo 
comparison). Overall, active medications resulted in a significant, clinically modest reduction of symptom 
severity on the Clinician Administered PTSD Scale (CAPS) (Blake et al, 1995) (-6.10 points, n=4112). 
Paroxetine provided the largest reduction of CAPS scores (-10.65 points, n=1100), sertraline showed modest 
effects (-4.35 point, n=1260), and paroxetine was significantly more effective than sertraline (fixed-effects 
model: X2=10.37, p=0.001). Psychotherapy interventions include a group of therapies under the rubric of 
cognitive behavior therapy (CBT), somatic experiencing, and mindful/spiritual approaches. Trauma-focused 
CBT such as prolonged exposure and cognitive reprocessing provides significant treatment effects. However, 
trauma-focused CBT has limitations, such as high rates of non-engagement in treatment, high withdrawal rates, 
and a significant risk of becoming more symptomatic. Interventions that minimize exposure to trauma content 
such as imagery rehearsal therapy and stress inoculation training also have evidence of efficacy for PTSD. 
The Demand for Other Approaches Including Acupuncture. A national survey in 1997 showed that 42% of 
individuals used one of 16 complementary/alternative medicine (CAM) therapies in 1 year (Eisenberg et al, 
1998). Most commonly used were herbs/supplements, massage, chiropractic, spiritual healing, acupuncture 
(ACU). It was estimated that 4% had used ACU. Similarly, a large survey conducted by the Samueli Institute 
with the Department of Defense showed that >45% of active-duty military members used any CAM per year. 
ACU is commonly used by active-duty military and Veterans for PTSD. The HAIG 2010 survey reported that 
25% of VHA facilities offered acupuncture service onsite and 16% referred to non-VA providers, which implies 
that about two-fifth of VHA facilities offered acupuncture service or referred veterans to non-VA providers. 

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Acupuncture: Our Developmental Work. Given the potential value of interventions that minimize trauma 
exposure coupled with research showing that acupuncture had effects on symptoms related to PTSD, we 
developed an acupuncture intervention for PTSD. For a review about the efficacy of acupuncture for anxiety, 
depression, and insomnia see publications in Appendix 3 (Hollifield, 2011; Hollifield et al, 2007). The first step 
was to develop a standardized intervention for PTSD based on Traditional Chinese Medicine (TCM) practice. 
We conducted a textbook review of the potential points to use for symptoms of PTSD, an expert survey to 
obtain opinions about points to use, and then pilot diagnosis and treatment planning with 22 PTSD patients. The 
primary TCM disease patterns that best described PTSD were Heart Shen disturbances, Liver Qi (energy 
movement) stagnation, and deficiency in the Kidney system. An explanation of these disturbances and the 
treatment points developed for our trial is in our published report (Sinclair-Lian et al, 2006). 
PTSD Involves Complex Biology: Choosing Biological Outcomes 
Major summative findings indicate complex biology of PTSD including HPA axis dysfunction, autonomic 
nervous system (ANS) dysfunction, alterations in central nervous system (CNS) processes, and inflammatory 
dysregulation, all under complex gene – environmental interaction control (in (Hollifield, 2011), Appendix 3).  
Focus on ANS Peripheral Psychophysiological Responses (PPR). Detailed below, there is consistent 
evidence that indices of PPR we propose to use in this study distinguish PTSD from trauma control subjects, 
may change with acupuncture, and are good translational tools to assess fear conditioning and extinction. 
Theoretical Framework: Failure of Extinction is Central to PTSD Pathology. PTSD symptoms are thought 
to be classically conditioned by exposure to aversive sensory stimuli (unconditioned stimuli: US) during combat 
trauma that provoke a fear/stress response (unconditioned response: UR). Similar sensory stimuli in subsequent 
non-combat situations, such as fireworks (conditioned stimuli: CS) provoke the fear/stress response 
(conditioned response: CR). Over time, the CR/PTSD symptoms generalize because the CS and CR occur in a 
high number of daily situations. These situations provide signals (CS) of threat related to initial trauma (US). 
Most Veterans “learn” to extinguish the CR by distinguishing between CS and US. However, while extinction 
of the CR generally occurs for most combat Veterans, a significant minority of those exposed to combat 
develop PTSD (Kessler et al, 1995). The leading theory is that PTSD involves a failure of mechanisms involved 
in recovery and restitution of physiological homeostasis, possibly resulting from individual predisposition 
(Yehuda et al, 1995). These processes are collectively a failure of extinction of the stress response, and can be 
measured by subjective description, symptom reports, and biological testing. 
Failure of Extinction in PTSD: Assessing with PPR.  Physiological reactivity on exposure to CS is a core 
feature of PTSD. Research has demonstrated that individuals with PTSD have different physiological responses 
(e.g., startle, heart rate, skin conductance response) to CS compared to controls (Orr et al, 2000). 
The startle response, measured with electromyography (EMG) of the eyeblink, provides an ideal translational 
tool to investigate fear conditioning and extinction, since the amygdala is directly connected with the startle 
circuit (Davis, 1992; Grillon et al, 1999). Fear-potentiated startle is the relative increase in the startle magnitude 
elicited in the presence of a CS; this PPR measure can be used to index both the increase in fear during 
conditioning as well as the 
reduction of fear during 
extinction. Traumatized 
individuals with PTSD show 
exaggerated startle compared to 
trauma controls (Jovanovic et al, 
2010) during fear conditioning 
as well as during fear extinction 
(Norrholm et al, 2011c). 
Previous research indicates that 
impaired extinction is a good predictor of PTSD symptoms; specifically re-experiencing symptoms (Norrholm 

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et al, 2011c).  In our previous studies, we have seen this impairment in two patterns. First, in two separate 
combat PTSD cohorts fear does not reach equivalently low levels in patients compared to controls, even after 6 
blocks of extinction (Figure A) (Norrholm et al, 2011b).  Second, in two independent civilian PTSD cohorts we 
observed a pattern of slower extinction rate (i.e., levels of fear in PTSD subjects are higher in early- and mid-
extinction, but comparable to controls during late extinction) (Figure B). 
Heart rate variability, heart rate, and skin conductance are good translational tools for assessing fear 
conditioning and extinction. While disturbances of both resting physiological tone and stress-reactivity in PTSD 
are established, stress-reactivity to CS is more pathognomonic in PTSD (reviewed by Orr) (Orr et al, 2000). 
Across various stimuli, skin conductance (SC) is the most sensitive measure of general arousal, whereas heart 
rate (HR) is more specific to trauma-related cues (Boucsein et al, 2012). The parasympathetic nervous system 
(PNS) influences basal HR and exerts a wider range of cardiac chronotropic control than the SNS branch in 
humans (Porges, 1995). PNS vagal influence on the heart can be evaluated by quantifying heart rate variability 
(HRV), measured as the amplitude of rhythmic fluctuations in HR associated with breathing (respiratory sinus 
arrhythmia [RSA]) (Sahar et al, 2001). Cohen and colleagues reported significantly lower resting RSA in PTSD 
than in controls and the absence of a HRV response to trauma recall (Cohen et al, 1998). Sack reported 
evidence of low RSA during exposure to trauma-related stimuli in 31 patients with PTSD (Sack et al, 2004). In 
35 subjects who survived motor vehicle accidents who were monitored with 24-hour Holter ECG two days after 
the accident and evaluated for PTSD at 2 and 6 months after the accident, there was a global diminution of 
HRV associated with PTSD at both 2 and 6 months (Shaikh al arab et al, 2012). In another study, videotapes of 
varying emotional valence were presented to trauma-exposed participants with PTSD (n=26), trauma-exposed 
participants without PTSD (n=26), as well as non-trauma-exposed controls (n=18) while recording ECG and 
respiration. The PTSD group showed lower HRV than non-trauma-exposed controls at baseline (corrected for 
age) and throughout different affective conditions (Hauschildt et al, 2011). Recent work has shown that 
respiration rate and tidal volume contribute substantially to within-individual RSA variance (Schulz et al, 2009), 
and this group has developed a MATLAB toolbox for correcting within-individual effects of respiration rate 
and tidal volume on respiratory sinus arrhythmia during variable breathing, which we will adopt for this study. 
Evidence for Extinction Learning in PTSD Patients. To support the use of PPR as outcomes, it is crucial to 
know if the PPR abnormalities might be reversed with treatment of PTSD. 
A few published studies have reported PPR changes associated with treatment of PTSD. Orr and Roth reviewed 
a number of earlier studies (Keane & Kaloupek, 1982; Shalev et al, 1993; Boudewyns & Hyer, 1990) outlining 
the psychophysiological applications for assessing treatment outcome (Orr et al, 2000). 
A meta-analysis reviewed literature about improvement in extinction learning in both humans and animals 
following exposure therapies (Norberg et al, 2008). While subjects in these studies did not have PTSD, they had 
other anxiety disorders (e.g., social phobia, panic disorder, and OCD). In each case, the efficacy of exposure 
treatment was associated with improved extinction learning. One study showed progressively lower arousal 
with treatment compared to sham therapy, evidenced by decreasing HR and increasing HRV across treatment 
(Sack et al, 2008). A more recent study showed low physiological responding during script-driven trauma 
imagery extended up to 4 months after treatment, showing the durability of treatment effect (Brunet et al, 2014). 
PPR’s during a conditioning paradigm have also been shown to predict treatment outcome in patients with 
PTSD (Aikins et al, 2011). Patients who were able to demonstrate differential conditioned fear responses at pre-
treatment were more likely to display reductions in PTSD symptoms following duloxetine treatment, suggesting 
that conditionability is a potential biomarker for treatment outcome. As such, we may find that pre-treatment 
extinction learning is a predictor and/or a consequence of acupuncture treatment response. Jovanovic reviewed 
other conditioning studies related to PTSD, concluding that impaired safety signal learning and failure to 
extinguish conditioned responses are potential biomarkers for PTSD. The authors also call attention to the fact 
that future studies need to assess extinction learning both pre- and post-treatment to assess the efficacy of the 
treatment (Jovanovic et al, 2012). The studies reviewed only assessed extinction learning at baseline. The 
proposed research is thus a novel approach assessing biomarkers associated with PTSD and treatment outcome.    

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Acupuncture Has Effects on PTSD Biology and will Promote Extinction Learning 
A significant literature suggests that acupuncture is likely to reverse PPR abnormalities seen in PTSD. There are 
no studies to our knowledge about biological effects of acupuncture in human PTSD. A recent review, however, 
describes a large human and animal literature about biological effects of acupuncture in systems involved in 
PTSD (Hollifield, 2011). Since we will assess ANS PPR’s, we review information relevant to the ANS. 
Neural pathways and autonomic (ANS) physiology (in (Hollifield, 2011). Effective acupuncture, which has 
been shown to occur when the sensation of “de qi” is obtained (Hui et al, 2005), stimulates α-delta fibers in the 
skin or muscle, which terminate in laminae I and V of the spinal cord. Marginal cells (M) in the cord project to 
somatosensory cortex via spinothalamic tracts, and projections to the medial prefrontal cortex (mPFC) travel by 
spinoreticular tracts, reticular formation (RF), and thalamus. Lamina I also projects to the locus coeruleus (LC), 
which is the adrenergic control center of the brain. In addition, downward projections via the fronto-arcuate 
connection to the hypothalamus extend to the descending inhibitory pathways directly to the LC and to 
serotonin and adrenergic systems. Manual acupuncture (MA) causes a broad CNS response involving the 
mPFC, amygdala, hippocampus, hypothalamus, cerebellum, basal ganglia, and insula, assessed by multiple 
imaging techniques, dependent on acupuncture type and frequency of stimulation (Napadow et al, 2005). The 
literature is replete with data about specific and broader, orchestrated effects of either MA or electro (EA) 
acupuncture on ANS, immune and inflammatory, and genetic expression via neural and protein messengers.  
Acupuncture is generally sympathoinhibitory in animals (Middlekauff et al, 2001) and humans (Haker et al, 
2000), although EA may cause either excitation or inhibition of the sympathoadrenal medullary reflex 
depending on EA location (Mori et al, 2000). A review by our senior advisor, who has conducted acupuncture 
research over the past two decades, details ANS physiology of acupuncture (Longhurst et al, 2013). Stimulation 
at known acupoints activates underlying sensory neural pathways that project to CNS regions that ultimately 
regulate ANS outflow. A long-loop pathway involving the hypothalamus, midbrain, and medulla underlies EA 
modulation of reflex increases in blood pressure (BP). Excitatory and inhibitory neurotransmitters in the 
supraspinal CNS underlie processing of somatic input and regulation of ANS outflow during EA. Acupuncture 
also decreases BP through actions in the thoracic spinal cord (Longhurst et al, 2013). Other studies have also 
demonstrated ANS regulation in clinical conditions. Studies in animal models of tachycardia (Wang et al, 2009) 
and depression (Zhou et al, 2007) have found changes in the expected direction of central and peripheral 
monoamine transmitters. Three human studies showed a change in serum catecholamines (CATS). One 
compared EA with the medication Nicardipine and found that both decreased systolic and diastolic blood 
pressure and CATS (Wan et al, 2009). One compared MA to the medication fluoxetine for post-menopausal 
symptoms and found that CATS change with both interventions similarly (Zhou et al, 2007). The third found 
that EA plus psychotherapy compared to psychotherapy alone in anxiety was more clinically effective and was 
associated with a greater reduction of CATS (Zhu et al, 2008). 
Acupuncture and PPR. A growing literature about the effects of acupuncture on PPR is beginning to emerge, 
although these studies were not in human PTSD. For example, electrodermal activity (EDA) has been studied in 
relation to four commonly held tenets of acupuncture: 1) EDA at pathology-related acupuncture points are 
distinguishable from non-pathology points, 2) EDA measured at acupuncture points can assist in monitoring 
therapeutic progress, 3) EDA at acupuncture points can identify substances that are beneficial or toxic to an 
individual, and 4) acupuncture points have lower electrical resistance than the surrounding skin. Studies using 
auricular acupuncture for pain and drug abuse found that EDA was helpful to monitor therapeutic progress. A 
reduction of impedances and improved electrodermal balance along meridians during treatment corresponded 
with clinical improvement (Colbert et al, 2011).  
Change in HR and HRV with acupuncture has been studied. An examination of differences in PPR to varying 
forms of MA showed that high-frequency and low amplitude manipulation led to decreased BP and HR, while 
low-frequency and high amplitude manipulation resulted in an initial increased BP and decreased HR and a 
more marked long-term decrease in BP (Backer et al, 2002). Chang et al. found a decrease in low frequency 
spectral power of HRV (related to sympathetic activation) associated with acupuncture points along the 

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pericardium meridian compared to sham points (Chang et al, 2008). Additionally, HRV power spectral analyses 
were utilized to demonstrate an increase in sympathetic activation during the first minute of the acupuncture 
session which included stimulation (likely triggered by pain or de qi), and an increase in parasympathetic power 
during the time following stimulation in verum compared to sham acupuncture (Streitberger et al, 2008). 
How does change in ANS PPR translate to improved extinction learning? The study is novel in examining 
the effects of acupuncture on extinction learning. Our theoretical framework posits that failure of extinction 
learning is central to PTSD pathology. We theorize that acupuncture will change sympathetic/parasympathetic 
balance, lessen the subjective experience of anxiety and generalized perception of danger, which will promote 
extinction to CRs. We will assess anxiety, PPR and extinction learning as evidence. 
 
II. RESEARCH DESIGN & METHODS 
Design and Protocol Summary 
This is a 5-year study at the Long Beach VA 
Healthcare System (LBVA). Collaborating partners 
within the LBVA are The Program for Traumatic Stress’ 
Novel Therapies Unit developed and directed by PI 
Michael Hollifield, MD; the Integrative Medicine Clinic 
founded and directed by Co-I An-Fu Hsiao, MD PhD; the 
Research Healthcare Group led by Chris Reist, MD 
MBA; and the PTSD psychophysiology laboratory 
managed by Mahmood Novin, MD. External 
collaborating partners include our design and analytic 
experts Besa Smith, PhD from UCSD and National 
University and Tyler Smith, PhD, Chair of Community 
Health at National University; the developers of our 
psychophysiology laboratory Tanja Jovanovic, PhD 
and Seth Norrholm, PhD from Emory University and 
the Atlanta VA. 
Design. A two-arm, parallel-group, prospective 
randomized placebo controlled clinical trial to evaluate 
the efficacy of acupuncture for PTSD. 
Study Timeline. Start-up and final IRB approvals will 
be completed by month 6. Subjects will be accrued at 
2.5 per month from study month 7 to 44. All subjects 
will complete treatment by month 47 and follow-up 
assessment by month 48. Analyses for primary hypothesis and all reports will be completed by month 57. 
Participants and sampling. The sample frame is Veterans with chronic PTSD due to combat exposure seeking 
treatment at the LBVA or affiliated programs. The figure shows the flow of the project. Withdrawals prior to 
beginning intervention will be replaced. The sample size (90) provides adequate power to test primary 
hypothesis. 
Inclusion criteria are meant to recruit a relatively homogeneous yet generalizable sample of Veterans with at 
least moderate chronic PTSD due to combat trauma. Criteria are: (1) Veterans aged 18 to 55, (2) DSM-5 criteria 
for chronic PTSD on the Clinician Administered PTSD Scale (CAPS-5), and (3) at least moderate PTSD by 
having a total CAPS-5 score of > 26 and meeting criteria for each of 4 symptom clusters. Eligible persons will 
be allowed to have other symptoms that are commonly comorbid with PTSD (e.g., anxiety, mild to moderate 
depression), but these will not be inclusion or exclusion criteria. This strategy will provide a feasible and 

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generalizable sample of those with chronic PSTD. Women and minorities will be recruited. 
Definition of “PTSD due to combat trauma:” Subjects must have PTSD due to a traumatic event in a combat 
zone. This may be any type of trauma, AND PSTD may be complex (i.e., combined war event, sexual event, 
MVA, etc). 
We would ideally include an older age range of Veterans to increase sample frame and generalizability. 
However, autonomic nervous system (ANS) function (sympathetic/parasympathetic balance) begins to change 
at about age 55 (Pascualy et al, 1999; Shibasaki et al, 2013; Veith et al, 1988). Since acupuncture may work via 
the ANS, and since exploratory hypotheses are dependent on ANS functioning, and the ANS age-related 
changes are difficult to detect to rationally exclude subjects, the best choice is to exclude those older than 55. 
Exclusion criteria are meant to keep out individuals with characteristics that are known to be PTSD treatment 
confounds, that may significantly affect biological assessment, that indicate past non-adherence or treatment 
resistance, or who may be put at risk of harm. Criteria are: (1) current and past six-months psychosis, (2) 
substance dependence (evidence of tolerance and/or withdrawal) within the past 6 months, (3) thyroid disease, 
(4) decisional incapacity (e.g., dementia), (5) centrally acting medications that have a potential effect on 
biological expression (e.g., beta-blockers, opiates, and >10mg equivalent of diazepam/day), (6) pain levels 
requiring opiate medications, (7) known exposure to chemicals or physical trauma that cause neuropsychiatric 
sequelae, (8) severe depression (Beck Depression Inventory-II score >30) that is deemed more clinically 
significant than PTSD, since this may bias accurate PTSD diagnosis and biological measures, (9) a diagnosed 
and untreated sleep breathing disorder (SBD) which is a treatment confound, (10) a high risk of a SBD as 
indicated by snoring >50 of nights plus one of (a) any witnessed apnea, (b) feeling non-refreshed in the morning 
>50 of mornings, or (c) daytime sleepiness indicated by falling asleep with routine tasks such as watching TV 
or reading, (11) non-response to >2 evidence-based PTSD treatments (adequate medication of 12 weeks or 
completion of PE, CPT or an intensive program), (12) treatment non-adherence indicated by stopping treatment 
or >3 missed appointments in the course of a PTSD EBT, (13) high dissociation as indicated by a score of >25 
on the Dissociative Experiences Scale – II (Bernstein & Putnam, 1986), (14) past chronic PTSD prior to 
military service, (15) current active psychotherapy for PTSD, (16) having acupuncture in the past year, or (17) 
pregnancy. A person who is on a stable dose (8 weeks) of medication for depression, anxiety, PTSD, or for 
sleep, or any other psychoactive medication that may confound the study, and who meet entering criteria and 
will continue these medications for the duration of the trial will not be excluded (see Clinical Protocol Detail). 
 
III. Procedures 
Recruitment. A two-stage detection method will be utilized to identify a sample of PTSD treatment seekers. 
Based on our previous study, we expect a 15% drop-out rate prior to the start of intervention; these will be 
replaced. Subjects who withdraw after starting treatment will not be replaced: based on our previous study we 
expect a 10% rate. This would leave 40 in each intervention group for a treatment completion analysis. Data of 
subjects who withdraw at any time after randomization will be retained for intent-to-treat analyses. 
Stage I: Screening for Inclusion/Exclusion. The PM/RA will contact potential subjects and ask them to 
provide written informed consent for study screening. Those who consent will be assessed with screening 
questions for inclusion and exclusion criteria, availability, and willingness to participate in the study. This visit 
may be conducted in person or by phone and will take about 20 minutes. 
Stage II: Inclusion Confirmation. The assessor will administer The CAPS-5, a modified Structured Clinical 
Interview for Diagnosis DSM-5 (SCID-5, now modified) (First et al, 2001), and the Dissociative Experiences 
Scale-II (Bernstein & Putnam, 1985) to assess inclusion and exclusions and further assess willingness and 
capacity to participate (i.e., have time and motivation). The Deployment Risk and Resiliency Inventory (DRRI) 
combat experiences scale and preparedness scale (Vogt et al, 2008) will be administered to aid group allocation. 
The study PI will assess current medications as potential exclusions. This visit will take about 2 to 3 hours. 

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After confirmed inclusion, the PM will reiterate the schedule, group allocation and compensation, and obtain 
written informed consent for participation. This will include informed consent to be videotaped to assess 
treatment fidelity. All hard and electronic data forms will be identified only by SID#. The clinical assessor will 
assess participants at each time point blind to group allocation. This procedure will keep the assessor blind to 
intervention allocation, and investigators and clinicians blind to assessment data to minimize performance and 
outcome detection bias. 
Randomization to intervention. The 90 subjects will be allocated to intervention group by a computer-
generated adaptive randomization procedure. Because of the adequate but still modest sample size in this study, 
simple randomization may not provide group equality on variables that affect outcome. Adaptive randomization 
is better suited to provide group equality if there is some knowledge about what variables affect outcome. The 
technique of minimization, for example, is one type of adaptive randomization. While this technique may risk  
subversion or technical error (Hewitt et al, 2006), minimization has been shown to be the best method of 
ensuring excellent balance between groups for several prognostic factors in small to moderate samples (Scott et 
al, 2002; Treasure et al, 1998), where blocking and stratification are not effective in small trials. With 
minimization the treatment allocated to the next participant enrolled in the trial depends on the characteristics of 
those participants already enrolled to minimize the imbalance across multiple factors. Minimization aims to 
ensure treatment arms are balanced with respect to predefined patient factors as well as for the number of 
patients in each group. Simulation studies show that minimization provides better balanced treatment groups 
when compared to randomization methods such as permuted blocks within strata (Scott et al, 2002). While there 
is still very little work about factors that predict outcome in PTSD, one study in Veterans showed that combat 
exposure and pre-deployment preparedness accounted for significant outcome variance using standard 
exposure-based psychotherapy (Price et al, 2013). There are also data suggesting gender effects of emotional 
disclosure interventions for PTSD in non-Veteran subjects (Ironson et al, 2013). As such, allocation to group 
will use an adaptive randomization designed to provide group equality in descending priority on: (1) number in 
each group, (2) combat exposure, (3) pre-deployment preparedness, and (4) gender. This will be accomplished 
by using a software program – minim – that will be adapted for the study by the PI and Dr’s. Smith. One 
potential problem of adaptive randomization is added organizational complexity and possible subversion of the 
randomization. Dr. Besa Smith will work with the DA to ensure that the program is clear and easy to use, and 
they will “sample enroll” 20 Veterans from our program prior to the study to demonstrate ease and 
effectiveness. The risk of subversion will be controlled by having only one person (DA) manage the minim 
program and discuss ongoing enrollment statistics with only the statisticians. 
The DA will assign each subject a Treatment ID number (e.g., TID# A1 to A45 for ACU) and consecutive study 
ID numbers (i.e., SID# 1 - 90), which will be the only number on hard copies of documents to conceal 
allocation from all investigators and other staff. The DA will be the only study staff that will be able to link both 
SID and TID numbers to subject and will be solely responsible for providing the clinician with treatment 
allocation. Other study personnel will be blind to this process and will only see the SID#.  
Interventions. Group 1 will receive ACU delivered in 1-hour sessions, twice per week for 12 weeks, Group 2 
(placebo control), will receive MIN, also delivered in 1-hour sessions, twice a week for 12 weeks. (See Clinical 
Protocol Detail). 
Subjects in both groups will receive an equivalent amount and kind of time, empathy, setting, and assessment. 
Both verum and control protocols will include language currently in our acupuncture clinical trials manual for 
greeting, interacting with, and closing a session. 
Informing subjects about group allocation. MIN acupuncture is indistinguishable from verum ACU to 
subjects who have not received this intervention and to most people independent of acupuncture experience. 
However, blinding may be compromised unless care is taken during allocation, informed consent, and the actual 
sessions. Clinical Protocol Detail has a more complete description about how study procedures inform subjects 
about group allocation in a way that maintains integrity of blinding to intervention. These procedures include 
how the room and materials are set up, how interventions are discussed, and how informed consent is delivered. 

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Group 1: Verum acupuncture (ACU). Individual treatment sessions are 1 hour twice per week for 12 weeks, 
and reflect clinical practice with an interview (10 minutes), pulse and tongue observation (5 minutes), standard 
needling, and needle retention (30 minutes). Subjects receive a standard acupuncture point prescription defined 
in our previous study and chosen for the most likely TCM diagnostic patterns for PTSD. An alternating by 
session front and back treatment will be used to avoid point fatigue (tolerance due to frequent use). The front 
treatment is comprised of 11 needles, bilaterally at LV3, PC6, HT7, ST36, SP6, and at the single Yintang point; 
the back treatment is 14 needles, bilaterally at GB20, and UB14, 15, 18, 20, 21, and 23. In addition to the 
standard points, three additional points (chosen from a list of 15 points) will be chosen to address a subject's 
constitution based on the TCM diagnostic patterns. A complete description of the experimental intervention is 
provided in published reports (Hollifield et al, 2007; Sinclair-Lian et al, 2006) (PMID: 17568299 and 
16494568).  
Group 2: Sham acupuncture: minimal needling (MIN). Individual treatment sessions are 1 hour twice per 
week for 12 weeks. Three elements define minimal needling in this study. The first is the location of the 
needles, which are 2 cm lateral or medial to actual points, which are not associated with PTSD (Sinclair-Lian et 
al, 2006) and are not expected to effect PTSD symptoms. The second is the insertion depth, which will be 
superficial (<0.25 inch) in MIN compared to verum. The third is the relative absence of stimulation, although 
there will be a non-functioning stimulator used to complete the sham effect. The acupuncturist will ensure that 
no DeQi sensation is obtained. The protocol uses 11 front and 14 back points for the sham acupuncture group 
(MIN) to match the number and body position (alternating prone and supine) of points in the verum 
acupuncture group (ACU). 
Compensation Plan. Subjects will be compensated for their time and travel to participate in the study. Subjects 
will be compensated $25 each for initial and post-treatment assessment, $50 for each of 3 biological 
assessments, and $50 for completing the intervention for a total possible compensation of $250 per subject. 
Protection of Human Subjects: See Human Subjects Detail 
 
III. Data Management 
Data collection. The program manager (PM) will track recruitment and retention. A clinical assessor will 
conduct diagnostic interviews and questionnaire evaluations pre-, mid-, and post-intervention blind to group 
allocation. All pre-, mid-, and post-treatment biological measures will be conducted and analyzed by the 
psychophysiologist and consultants, blind to group allocation.  
Assessment, Data Collection, and Schedule. Instruments and other data collection tools and their description 
are in the Assessment Detail. This strategy includes repeat measures yet minimizes response burden. Our goal is 
to test for effect signal. It is premature to evaluate durability and not ethical to keep subjects in a protocol where 
they may not be receiving effective treatment (particularly true of MIN), so we will not include a six-month 
follow-up period. Instead, a one-month follow-up will test symptoms and functioning and be utilized to re-
connect participants to clinical services. Data collection at mid-point of treatment is warranted to replicate mid-
treatment findings from our first trial. Such a finding may help determine dose effects and plan a dose-finding 
trial.  
Outcome measures. The primary outcome is change in PTSD symptom severity from pre- to post-treatment. 
We hypothesize a large pre- to post-treatment effect for ACU (d > 0.8) and at least a mild treatment effect (d > 
0.30) of the difference between groups (ACU vs MIN) pre- to post-treatment, with 80% probability of detecting 
a true group difference at p<0.05 (2-sided). Main biological outcome (secondary outcome) is change from pre- 
to post-treatment in PPR (decreased startle by EMG eyeblink). 
 
IV. Statistical Plan and Data Analyses 

Protocol Rev 3. 4.10.2018 MH 
 
General Approach.  General linear mixed models (GLMM) are capable of handling multiple underlying 
distribution and model structures through link functions, such as repeated measures random effects models of 
continuous outcomes (identity link), repeated measures logistic models (logit link), and Poisson and negative 
binomial models (log link). In addition to modeling global fixed effects across subjects, GLMM can also 
model individual subject random effects.  Survival analysis allows for the assessment of time to event 
modeling using probability estimates on survivor functions and estimates of hazard ratios. Time to event 
modeling using Cox proportional hazard modeling allows for all subjects to contribute information to the model 
up until occurrence of event, drop out, or end of study. Cox Proportional Hazards modeling will be used to 
investigate for effect-size of the treatment by allowing subjects to contribute their information to the model 
while they are being observed and censored once they are no longer being observed (loss to follow-up or end of 
study period). Further, using the Cox modeling we will investigate for time dependencies and informative loss 
to follow-up.  In the case where dropouts may be associated with the treatment assignments, we will leverage 
intention to treat methodology and construct a piecewise random effects model with both "on-" and "off-
treatment" slopes. GLMM will be used to evaluate the primary clinical hypothesized effects of treatment (ACU) 
on the clinical outcome of PTSD symptom severity (CAPS) over time (mid- and end-treatment, and 1-month 
follow-up), controlling for baseline severity of symptoms and demographic characteristics (e.g., age, gender) in 
comparison with placebo control group (MIN) with assumption of intent to treat. Cohen’s d within and between 
subjects will be calculated. Interaction terms will be included in the models to evaluate treatment fidelity and 
treatment expectancy as potential moderators. 
GLMM will also be used to evaluate the secondary biological hypothesized effects of treatment on pre- to post-
treatment in PPR (decreased EMG eyeblink). These same statistical procedures (GLMM, survival analysis, and 
Cohen’s d with intent to treat) will be applied to evaluate exploratory outcomes: clinical symptoms comorbid 
with PSTD, PPR (HR, HRV, SCR), and PTSD diagnosis. 
Statistical Analyses, Primary Hypothesis. Prior to the application of any statistical modeling, underlying 
assumptions and conditions will be examined. Univariate analyses, including tests of distribution assumptions, 
t-tests, and chi-square tests will be conducted to determine possible significant covariates to be included in 
further multivariable modeling as well as to investigate efficiency of randomization techniques. All models will 
be assessed for goodness of fit as well as other diagnostics including assessment for collinearity performed on 
all covariates chosen for subsequent analyses. Repeated measures analysis of variance will be used to formally 
test the null hypothesis of no differences in baseline PTSD symptom mean levels and subsequent retest of 
PTSD symptom mean levels while simultaneously adjusting for any significant covariates. All models will be 
run accounting for any potential confounders. Analyses will be performed assuming intent to treat and 
informative loss-to-follow up will be investigated. Additional analyses will be conducted to determine 
interactions and mediating effects while simultaneously adjusting for other covariates in the model. 
Assumptions for Power Calculations. Assumptions are based on interpolated data since primary outcomes in 
our first ACU study were assessed with the PSS-SR scale and there are no PTSD studies using MIN as the 
sham. Furthermore, to be consistent with major PTSD research, we will use the CAPS-5 (DSM-5 version) as the 
primary outcome, and there are as of yet no completed clinical trials using CAPS-5. In our first study, mean pre-
treatment PTSD severity score was about 62% of maximum (31.55 of 51). ACU mean decreased 50% - 31.33 
(10.1) to 15.65 (13.95) and wait-list mean decreased 9.3% - 30.79 (9.54) to 27.92 (12.33) at post-treatment. We 
thus assume that subjects will have a baseline mean CAPS-5 score of 50 (10) and a 50% reduction of symptoms 
and a 38% increased variance (CAPS-5 = 25; SD = 13.8) with ACU. There are sparse data about effects of 
MIN, noting a 33% improvement compared to pharmacological treatment only, and a 33% less effect than ACU 
in the Shen study. A 2010 Cochrane systematic review of over 200 trials investigating 60 clinical conditions 
about general placebo effect found placebos to not have important clinical effects but may influence patient-
reported outcomes in some situations (e.g., pain and nausea). The pooled relative risk calculated for placebo 
was 0.93 (effect of only 7%) but significant. Confidence intervals are generally wide in the placebo arm. 
Several clinical and methodological factors were associated with higher effects of placebo. Since our study 

Protocol Rev 3. 4.10.2018 MH 
 
includes some of these factors, and since we expect MIN to have some physical effect, MIN could provide an 
effect as much as 33% with a wider variance. This would predict mean CAPS-5 scores (MIN) at end-treatment 
of 33.5 (SD 15).  The conservative prediction is mean CAPS-5 reductions of 25 points with ACU and 16.5 
points with MIN, an 8.5-point difference with a pooled SD of 14.4. Given our experience and data about 
placebo effect, we can modestly expect a 12 point between group CAPS-5 difference and a pooled SD of 15. 
Treatment Effects, Power and Sample Size, Primary Hypothesis. “The efficacy of verum acupuncture 
(ACU) for PTSD symptom severity will be large (pre- to post-treatment Cohen’s d > 0.8), and significantly 
better than sham acupuncture (MIN) (between group Cohen’s d > 0.30, with 80% probability of detecting a true 
group difference at p<0.05 (2-sided).” 
Effects. The conservative assumptions noted above will result in pre- to post-treatment Cohen’s d = 2.07 within 
group (ACU) and between group (post-treatment difference) Cohen’s d = 0.59, which will prove the null 
hypothesis false and show a large treatment effect for ACU and a moderate between-group effect size. 
Sample size needed and power. The conservative assumptions would require a total of 90 patients in a two-
treatment parallel-design to provide a probability of 80 percent to detect a treatment difference at a two-sided 
0.05 significance level. Modest assumptions of a 12-point difference with a pooled SD of 15 requires a total of 
50 patients with power of 0.80 at alpha <0.05. 
This was determined using a formula for a random effects modeling (Montgomery, 1991), which may 
determine the necessary sample size to detect a statistically significant difference in treatment/control group 
means at different levels of projected effect differences. 
n = a 
         
Where: 
    = measure of noncentrality parameter to estimate the standard normal probability of making a type II error 
n     =   number of replicates necessary for each treatment 
a    =   number of treatments (a=2) 
     = estimated standard deviation 
  =  difference in baseline and post treatment 
Table. Examples of sample sizes necessary for significance testing at different mean and SD’s (between group: 
treatment (ACU) and control (MIN)) for PTSD severity (primary outcome) at power = 0.80. 
Mean difference between ACU and MIN PTSD 
severity scores post-treatment 
 
Total N Using Formula Above 
 
8.5 
12 
14.4 
15 
20 
62 
90 
96 
162 
 
12 
12 
15 
20 
32 
50 
86 
 
Recruitment goals are N=90, 45 per group. With a post-randomization attrition rate of 10% we will have at least 
40 individuals in each group. Considering attrition, the above table indicates that for an average difference in 
means of 12 at end-treatment with a standard deviation of 15, a total sample size of 50 (25 in each group) would 
be more than adequate to report a statistical difference with 80% power. If differences in treatment group means 
were found to be larger than 12, we would need even fewer subjects in our treatment groups to achieve 
statistical significance. 

Protocol Rev 3. 4.10.2018 MH 
 
PPR Data Recording and Reduction. A description of the procedure/data is in Appendix 4. Data reduction 
and analyses will follow current established protocols in our lab (Norrholm et al, 2011a). Data will be collected 
with the BioSemi recording software (BioSemi B.V, Amsterdam, Netherlands) and the resulting data will be 
exported to Mindware software (Mindware Technologies LTD, Gahanna, OH) for data reduction and generation 
of analyzable variables.  
Startle data reduction for analyses. The raw EMG signal will be recorded at a rate of 1000 Hz throughout the 
experimental session using a 28 Hz high pass and 500 Hz low pass filter (as recommended by guidelines for 
human eyeblink startle in Blumenthal et al., 2005; Psychophysiology, 42:1-15). Raw signals will be stored and 
exported for analysis in microvolt (µV) values.  
Skin Conductance Response. Skin conductance responses are scored as the largest amplitude responses 
beginning in a window of 1 to 3 seconds following stimulus onset. A response is defined as having amplitude 
greater than 0.01 µS relative to the pre-stimulus baseline (Boucsein et al, 2012). 
Heart rate. Average heart rate (HR), the standard deviation of the HR, power of high frequency (HF), low 
frequency (LF), very low frequency (VLF) components, % power of LF (%LF [of VLF+LF+HF]) and of HF 
(%) and the ratio of the LF over the HF (LF/HF ratio is used as an indirect autonomic balance index) of HRV 
are calculated as cardiac activity measures. Artifact-corrected 3-min long recording epochs are analyzed with 
FFT to assess HRV. Inter-beat Intervals (IBIs) will be scored as the time difference between successive R 
waves in the ECG signal. IBIs will be used as the dependent variable analyzed instead of heart rate because of a 
lowered susceptibility to artifact due to differences in baseline values (Stern et al., 2001). A window of 3 
seconds pre-stimulus onset to 6 following stimulus onset will be scored. Instantaneous IBIs will be recorded at 
half-second intervals during the pre- and post-stimulus time windows. A difference score between the average 
pre-stimulus IBI for each trial and each post-stimulus IBI value will be computed for each trial. IBIs will later 
be converted heart rate (beats per minute) for more readily interpretable post-analytic write-ups. 
Respiration. Respiration will be scored in a similar fashion to the ECG data and reported in interbreath 
intervals. Peak detection of each positive deflecting curve in the breathing cycle will be manually reviewed 
visually to assess accuracy. Interbreath intervals will later be converted to respiration rate (breaths per minute) 
for ease of interpretation.  
 
 
 
 
 

Protocol Rev 3. 4.10.2018 MH 
 
Clinical Protocol Detail 
 
Interventions. All subjects will be allocated to intervention group by a computer-generated adaptive 
randomization procedure. Selected participants will go through a preliminary phase to assess if there are 
specific acupuncture points that change heart rate and heart rate variability more than others during the 
psychophysiology assessment. 
Group 1 will receive verum acupuncture (ACU) (experimental intervention) delivered in 1-hour sessions, twice 
per week for 12 weeks. 
Group 2 will receive minimal acupuncture (MIN) (sham placebo control), also delivered in 1-hour sessions, 
twice a week for 12 weeks. 
Subjects will be blinded to intervention (i.e., if experimental or sham). Clinical assessor(s) and investigators 
will be blinded to randomization. The acupuncturist cannot be blinded, and so will follow a standardized 
protocol to minimize intervention bias and treatment fidelity will be assessed. 
 
Maintaining Blind and Non-specific Treatment-related Effects 
Informing subjects and maintaining blind about group allocation. MIN acupuncture is indistinguishable 
from verum ACU to subjects who have not received this intervention and even to most people independent of 
acupuncture experience. However, blinding may be compromised unless care is taken during allocation, 
informed consent, and the actual sessions. McManus and colleagues have described practical steps to take 
before, during, and after each session to not compromise subject blinding using verum versus sham acupuncture 
(McManus et al, 2007). We will adopt these steps, which include how to set up the room and materials prior to 
treatment, the materials to have on hand, and how to insert, manipulate, and remove the needles. McManus 
utilized these procedures in an RCT (N = 135), providing 8 sessions over 4 weeks using about 10 needles per 
session and were successful by having 71% of those receiving sham and 81% of those receiving verum (p = 
0.20) believe they received “real” treatment. Another important procedure for maintaining subject blinding is 
the construction and delivery of the informed consent. Subjects will all be informed that they will receive the 
standard dose of paroxetine, which is FDA approved for PTSD, and that there are “two types of treatments that 
involve acupuncture needles” or “two forms of treatment with needles” that will be used during this clinical 
trial, and that, they will be randomly allocated to receive either one or the other treatment. They will not be told 
the name or type of each protocol. If they ask about our expectation of effects, they will be told that we do have 
predictions, but that we cannot share with them those predictions. Any questions they ask about the needles or 
technique will be responded to with a structured answer that will be part of the training of all staff prior to the 
trial, such as, “as mentioned in the consent, there are two types of acupuncture treatments being used, and you 
may receive either one during any given session.” This approach is necessary to ensure the best blinding for this 
trial and is ethical since the evidence is not yet available to say that either verum or sham is known to be 
superior treatment for PTSD.  
Controlling for non-specific treatment-related effects. In this study, it is critical for those in the control group 
(MIN) to receive an equivalent amount and kind of time, empathy, setting, and assessment as those in the verum 
acupuncture group (ACU). Both verum and control protocols will include language currently in our acupuncture 
clinical trials manual for greeting, interacting with, and closing a session. Prior to the first session, each subject 
will meet with the acupuncturist who will conduct a Traditional Chinese Medicine (TCM) diagnostic session. A 
protocol example from our first acupuncture for PTSD study is Appendix A to this Attachment and included 
pragmatics and acupuncturist behavior. Note that this example differs in content from the proposed study. On 
funding, a protocol manual will be developed. 
 
Outline of Steps of Procedures and Interventions 
Step one: Conduct informed consent and conduct pre-treatment evaluation 

Protocol Rev 3. 4.10.2018 MH 
 
Step two: Randomization to group 
 
Subjects will be allocated to group by adaptive randomization. 
Step three: Begin and continue ACU or MIN interventions 
Step four: After 12-week intervention, stop ACU and MIN and conduct End-Treatment Assessments 
Step six: At the end of follow-up period (planned one month), determine how and where to transition 
subject to clinical care 
Note: One task of Data Safety and Monitoring on funding will be to review the protocol and advise the 
investigators about rules for continuation or discontinuation of each subject in the study and in the follow-up 
period. It may be unethical to continue Veterans in the follow-up period if there is no pre- to post-treatment 
reduction in CAPS. Furthermore, we are most interested in whether there is effect maintenance in those who 
have responded to treatment, so it may be scientifically meaningless in addition to the ethical dilemma to 
continue non-responders into the follow-up period. In this A1 revision, our primary goal is to determine if ACU 
provided effect (signal) compared to a placebo, and the follow-up period is not to primarily determine durability 
of treatment but to ensure safety and clinical follow-up planning. Our statistical methods will be able to manage 
data in an intent-to-treat model if subjects are withdrawn. Our current plan is to define a response as a CAPS-IV 
equivalent drop of 10 points (the value for CAPS-5 still needs to be determined). Those who have not had a 
response would have the option to withdraw and re-initiate clinical treatment immediately. Of course, any 
subject may withdraw at any time.  
 
Description of Intervention Protocols 
Recruitment of participants currently on medications for PTSD. It may be ideal to recruit subjects who are 
medication naïve, but this is not feasible in this single site study. Approximately 55% of Veterans with PTSD 
who are entering three of our current studies (a DoD funded multi-site trial of prolonged exposure with vs 
without virtual reality, Diefede PI, Reist, Long Beach site PI; a VA national cooperative studies program 
comparing prolonged exposure to cognitive processing therapy – CSP #591, Schnurr et al PI’s, Hollifield Long 
Beach site PI and executive committee member; an industry sponsored two-site RCT of Vilazodone vs. placebo 
for PTSD, Hollifield and Ramaswamy Co-PI’s) are on a medication when entering the trial, most often an SSRI. 
In the first two mentioned studies, the subjects can stay on the medication (with rules), and for the third study 
we offer a wash-out if the current medication has not been established for a long period or if effects are neutral 
or negative. We will thus offer a similar procedure in the proposed study to the first two mentioned studies, and 
the subject must be on a stable dose for 8 weeks or longer. 
 
Verum acupuncture (ACU). Individual treatment sessions are 1 hour twice per week for 12 weeks, and reflect 
clinical practice with an interview (10 minutes), pulse and tongue observation (5 minutes), standard needling, 
and needle retention (30 minutes). Subjects receive a standard acupuncture point prescription defined in our 
previous study and chosen for the most likely TCM diagnostic patterns for DSM-IV PTSD: Liver Qi stagnation 
(LV Qi); Heart Shen disturbance (HT Shen), and Kidney deficiency. An alternating by session front and back 
treatment will be used to avoid point fatigue (tolerance due to frequent use). The front treatment is comprised of 
11 needles, bilaterally at LV3, PC6, HT7, ST36, SP6, and at the single Yintang point; the back treatment is 14 
needles, bilaterally at GB20, and UB14, 15, 18, 20, 21, and 23. In addition to the standard points, three 
additional points (chosen from a list of 15 points) will be chosen to address a subject's constitution based on the 
TCM diagnostic patterns. The full protocol and the outcome of this protocol in PTSD was empirically 
developed and tested in our previous study, and is in the published papers (Hollifield et al, 2007; Sinclair-Lian 
et al, 2006) (PMID: 17568299 and 16494568), which may be found in Attachment 2.  Table 1 below shows the 
standard front and back points for the primary patterns that are used for each subject and the possible additional 
points for the secondary patterns that are determined by TCM diagnosis. 
 

Protocol Rev 3. 4.10.2018 MH 
 
 
 
Disposable, stainless acupuncture needles (34-gauge Cloud Dragon) are inserted perpendicularly to a standard 
depth (from ¼" to 1½"). For subjects who are pain sensitive, Seirin needles maybe use because they are 40-
gauge and better tolerated. Acupuncture needles are inserted with an introducer and are manually manipulated 
with insertion with the goal of obtaining “de Qi.” The acupuncturist feels sensation from needle manipulation 
and the patient feels soreness or fullness but not sharp pain. After de Qi is achieved, microalligator clips and 
electrodes to a battery-operated pulse generator connected to the negative pole will be attached to needles at 
HT7 and ST36, and microalligator clips and electrodes connected to the positive pole will be attached to needles 
at PC 6 and SP6 (pairs HT7 – PC6 and ST36 – SP6). When the subject receives the back points, the electrodes 
will be attached to UB15 and UB20 (neg) and UB 14 and UB21 (pos), respectively (pairs UB15 – UB 14 and 
UB20 – UB21). An EA stimulator made by Pantheon Research (Pantheon 12-Pro) will be used because this 
stimulator has high fidelity in delivering electrical output. Mixed electrical frequency (alternating between 2 Hz 
and 100 Hz) will be used because prior studies have shown that it has greater impact on ANS and CNS 
activities compared with fixed electrical frequency (Han et al., 2013). Subjects will be told that they may or 
may not feel the stimulation. After 15 minutes, the clinician will enter the room and manually manipulate the 
needles that do not have electrical stimulation to obtain de Qi. After 30 minutes of needle retention the clinician 
Table 1. Acupuncture Points for The Treatment of Posttraumatic Stress Disorder 
Primary Patterns (Standard points for all subjects) 
 
HT Shen 
Disturbance 
LV Qi Stagnation 
Kidney Deficiency 
Grounding points / 
Qi & Blood 
Deficiency 
 
Front 
points 
 
HT7, (PC6) and 
Yintang (even) 
LV3, PC6 (even) 
 
ST36, SP6 (even) 
 
Back 
points  
UB14, 15 (even) 
GB 20, UB18 (even) 
UB 23 (reinforce) 
UB 20, 21 (even) 
 
Secondary Patterns (Up to three points chosen) 
 
LV 
overacting 
on SP 
LV overacting 
on ST 
ST Fire 
LV Fire 
Phlegm-
Heat 
Phlegm-
Damp 
Front 
points  
LV13 
(reinforce) 
LV14 (reduce) 
ST44 (reduce) 
LV2 
(reduce) 
ST40 
(reduce) 
SP9 (reduce) 
Back 
points 
 
UB18 
(reduce)  
UB20 
(reinforce) 
UB18 (reduce)   
UB21(reduce) 
Du 14 
(reduce)  
UB21 
(reduce) 
Du 14 
(reduce) 
UB18 
(reduce) 
Du 14 
(reduce) 
UB21 
(reduce) 
UB20 
(reduce) 
 
 
 
 
 
 
 
 
HT 
Yin/Blood 
deficiency 
SP Qi/Yang 
deficiency 
KI 
Yin/Essence 
deficiency 
KI Yang/Qi 
deficiency 
LV 
Yin/Blood 
deficiency 
ST Yin 
deficiency 
Front 
points  
HT6 
(reinforce) 
SP3 (reinforce) 
KI6 
(reinforce) 
KI7 
(reinforce) 
LV8 
(reinforce) 
ST44 
(reinforce) 
Back 
points  
UB17 
(reinforce) 
UB15 
(reinforce) 
UB20 
(reinforce) 
UB23 
(reinforce) 
UB52 
(reinforce) 
UB23 
(reinforce) 
Du4 
(reinforce) 
UB23 
(reinforce) 
UB17 
(reinforce) 
UB18 
(reinforce) 
UB21 
(reinforce) 

Protocol Rev 3. 4.10.2018 MH 
 
will enter the room, manipulate the needles that do not have electrical stimulation to obtain de Qi, and then 
remove needles in a prescribed order after turning off electrical stimulation. 
Sham acupuncture (MIN). Individual treatment sessions are 1 hour twice per week for 12 weeks. Three 
elements define minimal needling in this study. The first is the location of the needles, which will be non-
acupuncture points not near points found in our development work to be associated with PTSD (Sinclair-Lian et 
al, 2006) and are points not expected to effect PTSD symptoms. The second is the insertion depth, which will be 
superficial (<0.25 inch) in MIN compared to verum ACU. The third is the relative absence of stimulation. There 
will be a non-functioning stimulator used to complete the sham effect. The acupuncturist will ensure that no 
DeQi sensation is obtained. The protocol uses 11 front and 14 back points for the sham acupuncture group 
(MIN) to match the number and body position (alternating prone and supine) of acupoints in the verum 
acupuncture group (ACU). Insertion will be 2 cm medial or lateral to the actual defined acupoints. The 11 front 
points will be near: bilateral LU7, bilateral LU6, bilateral SJ3, bilateral SI4, bilateral ST 34, and left SI 19. 
Microalligator clips will be attached to needles at LU6 (positive pole) connected with SJ3 (negative pole), and 
between SI4 (positive) and SI 19 (negative). The 14 back points will be near the following bilateral points: SI 9, 
SI 11, SI 15, GB 30, GB 32, GB 33, GB 34. Microalligator clips will be attached between SI 9 (positive) and SI 
14 (negative) and between GB 32 (positive) and GB 34 (negative). The microalligator wires will be connected 
to an electrical stimulator that is identical to and will deliver the same audiovisual stimuli as the one used for 
ACU; however, no electrical current will be passed through needles (Pantheon Research can modify their 
stimulator to maintaining the flashing green light without electrical current to be a pseudo-stimulator). Subjects 
in both ACU and MIN groups will receive identical time and attention in interview, pulse and tongue 
observation, and needle retention. Subjects will be told that they may or may not feel the stimulation. After 15 
minutes, the clinician will enter the room and touch but not manipulate the needles that do not have pseudo-
electrical stimulation. After 30 minutes of needle retention the clinician will enter the room, manipulate the 
needles that do not have pseudo-electrical stimulation, and then remove needles in a prescribed order after 
“turning off” pseudo-electrical stimulation. 
Justification for choosing minimal needling as sham control.  Sham procedures are not fully inactive and 
indistinguishable from verum acupuncture (Park et al, 2002). There are essentially 3 ways to conduct sham 
acupuncture using needles. Two involve needle insertion: (1) insertion and manipulation in the same manner 
but at purportedly “irrelevant” points, usually a few millimeters from actual verum points, or (2) superficial 
insertion at verum points, usually without manipulation to not elicit the “de qi” sensation. Each, or a 
combination of each, have been labelled “minimal needling.” Investigators have also used various gauge-size 
needles and very small monofilaments as insertive shams. The third type of sham (3) is non-insertive, where a 
blunt needle within an adhesive O-ring mechanism hits the skin and retracts without puncture. When this sham 
is used, the needles for verum acupuncture are also administered via the adhesive O-ring for blinding. Both 
insertive and non-insertive procedures probably influence expectation, sensation, and contextualization, and 
both have shown effects in brain areas controlling sensation, cognition, and affect (Kong et al, 2006). While 
two non-insertive needles have been developed and shown to be valid shams from the subjective patient view 
(the “Streitberger” and the “Park Sham Device”) (Park et al, 2002; Schnyer et al, 2008), these are far more 
cumbersome and very expensive compared to minimal needling. And, research has shown clinical differences 
between verum ACU and minimal (MIN) needling techniques, for example in a study of chemotherapy-induced 
emesis control (Shen et al, 2000) and blood pressure control (Flachskampf et al, 2007). In the Shen study where 
all patients had basic pharmacotherapy for emesis, emesis events and emesis free days were significantly better 
with ACU vs. MIN vs. pharmacotherapy only (events 5 vs. 10 vs. 15, respectively; free days 55% vs. 29% vs. 
20%, respectively). MIN is the best available sham control to verum ACU because they both are similar in all 
aspects except that MIN includes irrelevant acupoints and shallow insertion without obtaining DeQi. 
 
 
 

Protocol Rev 3. 4.10.2018 MH 
 
Psychoactive Medications Requiring 8 weeks 
stability 
Drug Classes 
Generic Names 
Trade Names 
OPIOID 
ANALGESICS 
ACETAMINOPHEN/ 
HYDROCODONE 
VICODIN 
  
ALFENTANIL HCL 
AFLENTA 
  
BELLADONNA/OPIUM 
BELLADONNA AND OPIUM 
  
BUPRENORPHINE  
BUPRENEX/SUBUTEX 
  
BUPRENORPHINE/ 
NALOXONE 
SUBONOXONE 
  
BUTORPHANOL 
TARTRATE 
STADOL 
  
CODEINE 
CODEINE 
  
CODEINE/ 
ACETAMINOPHEN 
TYLENOL-CODEINE 
  
METHADONE  
DOLOPHINE, METHADOSE, 
DISKETS 
  
MORPHINE 
DURAMORPH, AVINZA, 
ASTRAMORPH,  
DEPODUR 
  
OXYCODONE HCL 
OXYCONTIN 
  
REMIFENTANIL 
ULTIVA 
  
SUFENTANIL CITRATE SULFENTA 
OPIOID 
ANTAGONIST 
ANALGESICS 
NALTREXONE HCL 
VIVITROL, REVIA 
NON-OPIOID 
ANALGESICS 
ACETAMINOPHEN/ 
BUTALBITAL/ 
CAFFEINE 
ALAGESIC, ANOLOR, DOLGIC,  
DOLMAR, ESGIC,EZOL, FIORCET,  
GEONE, MARGESIC, MEDIGESIC,  
NONBAC, ORVIVAN, PERCAPS,  
REPAN, ZEBUTAL 
  
ASPIRIN/BUTALBITAL/ 
CAFFEINE 
FIORINAL, BUTALBITAL 
COMPOUND,  
FARBITAL, FIORTAL 
  
CLONIDINE HCL 
DURACLON 
  
TRAMADOL HCL 
ULTRAM, RYZOLT 
ANTIMIGRAINE 
AGENTS 
CAFFEINE/ 
ERGOTAMINE 
CAFERGOT, WIGRAINE 
  
DIHYDROERGOTAMIN
E MESYLATE Spray 
MIGRANAL 
  
SUMATRIPTAN 
SUCCINATE 
IMITREX 
BARBITURIC ACID 
DERIVATIVE 
SEDATIVES/ 
HYPNOTICS 
PHENOBARBITAL 
PHENOBARBITAL 

Protocol Rev 3. 4.10.2018 MH 
 
BENZODIAZ 
DERIVATIVE 
SEDATIVES/ 
HYPNOTICS 
ALPRAZOLAM 
XANAX 
  
CHLORDIAZEPOXIDE 
HCL 
LIBRIM 
  
DIAZEPAM 
VALIUM 
  
LORAZEPAM  
ATIVAN 
  
MIDAZOLAM HCL 
VERSED 
  
OXAZEPAM 
SERAX 
  
QUAZEPAM 
DORAL 
  
ESTAZOLAM 
PROSOM 
  
CLONAZEPAM 
KLONIPEN 
  
FLURAZEPAM 
DALMANE 
  
TEMAZEPAM 
RESTORIL 
  
TRIAZOLAM 
HALCION 
SEDATIVES/ 
HYPNOTICS, 
OTHER 
BUSPIRONE HCL 
BUSPAR 
  
CHLORAL HYDRATE 
NOCTEC 
  
ZOLPIDEM 
AMBIEN 
  
ZALEPLON 
SONATA 
  
HYDROXYZINE 
ATARAX, VISTARIL 
  
ZOPICLONE 
IMOVANE 
  
ESZOPICLONE 
LUNESTA 
ANTI- 
CONVULSANTS 
CARBAMAZEPINE 
TEGRETOL, CARBATOL, EQETRO 
  
DIVALPROEX  
DEPAKOTE 
  
FELBAMATE 
FELBATOL 
  
GABAPENTIN  
NEURONTIN, GRALISE 
  
LAMOTRIGINE 
LAMICATAL, LAMICTAL XR 
  
LEVETIRACETAM 
KEPPRA, KEPPRA XR 
  
OXCARBAZEPINE 
TRILEPTAL, OXTELLAR XR 
  
PHENYTOIN 
DILANTIN, DILANTIN 125,  
DILANTIN KAPSEALS 
  
PRIMIDONE 
MYSOLINE 
  
TOPIRAMATE 
TOPAMAX 
  
VALPROIC ACID 
DEPAKENE, STAZOR 
  
ZONISAMIDE 
ZONEGRAN 
ANTI- 
PARKINSON 
AGENTS 
APOMORPHINE 
APOKYN 
  
CARBIDOPA 
/LEVODOPA 
SINEMET, SINEMET CR 
  
ENTACAPONE 
COMTAN 

Protocol Rev 3. 4.10.2018 MH 
 
  
RASAGILINE 
AZILECT 
  
ROPINIROLE 
REQUIP, REQUIP XL 
TRICYCLIC 
ANTIDEPRESSANTS AMITRIPTYLINE HCL 
ELAVIL 
  
CLOMIPRAMINE 
ANAFRANIL 
  
DESIPRAMINE HCL 
NORPRAMIN 
  
DOXEPIN HCL 
PRUDOXIN, SINEQUAN, ZONOLAN,  
SILENOR 
  
IMIPRAMINE HCL 
TOFRANIL, TOFRANIL-PM 
  
NORTRIPTYLINE 
PAMELOR 
  
AMOXAPINE 
AMOXAPINE 
  
TRIMIPRAMINE 
SURMONTIL 
  
PROTIPTYLINE 
VIVACTIL 
MONAMINE 
OXIDASE 
INHIBITOR 
ANTIDEPRESSANTS 
PHENELZINE 
SULFATE  
NARDIL 
  
SELEGILINE 
ELDEPRYL, ZELPAR 
  
TRANYLCYPROMINE 
SULFATE 
PARNATE 
ANTIDEPRESSANTS
,OTHER 
BUPROPION HCL 
WELLBUTRIN 
  
CITALOPRAM 
HYDROBROMIDE 
CELEXA 
  
ESCITALOPRAM 
LEXAPRO 
  
FLUOXETINE  
PROZAC 
  
MIRTAZAPINE 
REMERON 
  
PAROXETINE 
PAXIL 
  
SERTRALINE 
ZOLOFT 
  
TRAZODONE 
DESYREL 
  
VENLAFAXINE  
EFFEXOR 
  
NEFAZADONE 
SERZONE 
  
DULOXETINE 
CYMBALTA 
  
MILNACIPRAN 
SAVELLA 
  
LEVONMILNACIPRAN 
FETIZMA 
  
VENLAFAXINE  
EFFEXOR 
  
DESVENLAFAXINE 
PRISTIQ 
  
VILAZODONE 
VIIBRYD 
  
FLUVOXAMINE 
LUVOX 
PHENOTHIAZINE/ 
RELATED 
ANTIPSYCHOTICS 
CHLORPROMAZINE 
THORAZINE 
  
FLUPHENAZINE 
PROLIXIN, PROLIXIN DECANOATE 
  
PERPHENAZINE 
TRILAFON 
  
THIOTHIXENE 
NAVANE 

Protocol Rev 3. 4.10.2018 MH 
 
  
THIORIDAZINE 
MELLARIL 
  
MESORIDAZINE 
SERENTIL 
  
TRIFLUOPERAZINE 
STELAZINE 
ANTIPSYCHOTICS,
OTHER 
ARIPIPRAZOLE 
ABILIFY 
  
CLOZAPINE 
CLOZARIL 
  
HALOPERIDOL 
HALDOL, GALDOL DECANOATE 
  
LOXAPINE 
LOXITANE, LOXAPINE, ADASUVE 
  
LURASIDONE 
LATUDA 
  
OLANZAPINE 
ZYPREXA, ZYPREXA ZYDIS,  
  
PALIPERIDONE 
INVEGA 
  
QUETIAPINE 
FUMARATE 
SEROQUEL 
  
RISPERIDONE 
RISPERDAL , RISPERIDOL CONSTA 
  
ILOPERIDONE 
FANAPT 
  
ASENAPINE 
SAPHRIS 
  
ZIPRASIDONE 
GEODONE 
LITHIUM SALTS 
LITHIUM 
LITHIUM 
AMPHETAMINES 
DEXTROAMPHETAMI
NE 
DEXEDRINE, ADDERALL 
  
AMPHETAMINE 
ADDERALL 
AMPHETAMINE 
LIKE STIMULANTS 
METHYLPHENIDATE 
CONCERTA, RITALIN 
  
DEXMETHYLPHENIDA
TE 
FOCALIN, ATTENDAE 
CNS STIMULANTS, 
OTHER 
CAFFEINE 
CAFFEINE, CAFCIT 
  
DONEPEZIL 
ARICEPT 
  
ERGOLOID 
MESYLATES 
HYDERGINE 
  
GALANTAMINE  
RAZADYNE 
  
MEMANTINE HCL 
NAMENDA 
  
PIMOZIDE 
ORAP 
  
PEMOLINE 
CYLERT 
  
RILUZOLE 
RILUTEK 
BETA BLOCKERS/ 
RELATED 
PROPRANOLOL HCL 
PROPRANOLOL 
ALPHA BLOCKERS/ 
RELATED 
PRAZOSIN  
MINIPRESS 
ALPH-2 AGONISTS 
CLONIDINE  
CATAPRES, KAPVAY, DURACLON,  
NEXICLON 
  
GUANFACINE 
INTUNIV, TENEX 
 
 
 

Protocol Rev 3. 4.10.2018 MH 
 
Assessment Detail 
 
Schedule and List of Data Collection Instruments 
 
Instruments and Assessments 
Baseline 
Mid 
treat-
ment 
End 
treat-
ment 
1-Mo. 
Follow
up 
6-Mo. 
Follow
up 
1. Screening, Diagnostics, and Trauma Exposure 
Screening Questionnaires 
X 
 
 
 
 
Clinician Administered PTSD Scale-5 (Blake et al, 1995)  
X 
 
 
 
 
Structured Clinical Interview for Diagnosis (First et al, 2001) 
X 
 
 
 
 
Dissociative Experiences Scale (Bernstein & Putnam, 1986) 
X 
 
 
 
 
Beck Depression Inventory – II (Beck et al, 1996) 
X 
 
 
 
 
Deployment Risk and Resilience Inventory-2 (Vogt et al, 
2008) 
X 
 
 
 
 
2. Primary Outcome (Clinical) 
PTSD Severity Score on CAPS-5 (Blake et al, 1995)  
X 
X 
X 
X 
X 
3. Secondary Outcome (Biological) 
PPR (startle) 
X 
 
X 
 
X 
4. Exploratory Outcomes 
PTSD Checklist-Military (PCL-5) (Weathers et al, 1993) 
X 
X 
X 
X 
X 
Beck Depression Inventory – II (Beck et al, 1996) 
X 
X 
X 
X 
X 
Hopkins Symptom Checklist-25 Anxiety Scale (Derogatis et 
al, 1974) 
X 
X 
X 
X 
X 
New Mexico Symptom Checklist Somatic Sc. (Hollifield et 
al, 2009) 
X 
X 
X 
X 
X 
Pittsburg Sleep Quality Index (Buysse et al, 1989) 
X 
X 
X 
X 
X 
Veterans RAND 12-item Health Survey (Selim et al, 2009) 
X 
X 
X 
X 
X 
PPR (HR, HRV, SCR) 
X 
 
X 
 
X 
5. Safety and Control Data (to be administered weekly or monthly) 
Aggression Questionnaire (Buss et al, 1992) 
weekly 
 
X 
X 
X 
Beck Depression Inventory – II items 9, 11, 17 
weekly 
 
 
 
 
Satisfaction with Care and Provider Scale (Unpublished) 
 
 
X 
 
X 
Intercurrent Health Resource Use Inventory 
X 
 
X 
 
X 
6. Treatment Fidelity and Expectancy 
Treatment Fidelity Assessment (Therapist Adherence Scale) 
selected 
 
 
 
The Credibility Rating Scale (Borkovec, 1972) 
selected 
 
 
 
 
Description of Instruments 
1. Screening and Diagnostics 
The Clinician Administered PTSD Scale (CAPS) (Blake et al, 1995) is a structured diagnostic interview for 
PTSD. The new CAPS-5 based on DSM-5 criteria will be used (CAPS-5 update, unpublished: Weathers et al, 
2013). As with previous versions of the CAPS, CAPS-5 symptom severity ratings are based on symptom 
frequency and intensity, except for items 8 (amnesia) and 12 (diminished interest), which are based on amount 
and intensity. However, CAPS-5 items are rated with a single severity score, in contrast to previous versions of 
the CAPS which required separate frequency and intensity scores for each item that were either summed to 
create a symptom severity score or combined in various scoring rules to create a dichotomous (present/absent) 

Protocol Rev 3. 4.10.2018 MH 
 
symptom score. CAPS-5 has 20 symptom items, each rated from 0 (absent) to 4 (severe). A rating of >2 is 
considered a positive score for diagnostic purposes. There are 4 symptom clusters: the Criterion B (re-
experiencing) severity score is the sum of the individual severity scores for items 1-5; the Criterion C 
(avoidance) severity score is the sum of items 6 and 7; the Criterion D (negative alterations in cognitions and 
mood) severity score is the sum of items 8-14; and the Criterion E (hyperarousal) severity score is the sum of 
items 15-20. The DSM-5 diagnostic rule requires the presence of least one Criterion B symptom, one Criterion 
C symptom, two Criterion D symptoms, and two Criterion E symptoms in addition to other impairment criteria 
(see “scoring” on CAPS). A DSM-5 CAPS cutoff score of >26 AND meeting each of the 4-symptom cluster 
criterion will be used for study inclusion. This is consistent with what will be used in the VA Cooperative Study 
#591, which is the first national study to use the CAPS-5 for diagnosis and treatment effect assessment. 
The Structured Clinical Interview for Diagnosis (SCID) (First et al, 2001) is the most frequently used diagnostic 
interview in psychiatric research for assessing diagnoses. The modules appropriate to inclusion and exclusion 
criteria will be used in this study by the clinical assessor to verify the presence or absence of PTSD diagnosis 
and to determine if exclusionary diagnoses are present. The updated DSM-5 version will be used; it is expected 
to be available by the time of funding/study start, as it is now being used in the national CSP 591 study 
comparing efficacy of Prolonged Exposure with Cognitive Processing Therapy (The PI for the proposed study 
is on the executive committee and is a site investigator for CSP 591) 
The Dissociative Experiences Scale (DES-II) (Bernstein and Putnam, 1986) is a 28-item self-report scale used 
to measure the frequency of dissociative experiences using a 10-point Likert scale with verbal quantifiers. Item 
scores range from 0 to 100. Total scores are calculated by averaging the scores of the 28 items, which refer to 
amnesia, depersonalization, derealization, absorption, and identity alteration. A score of 30 or more is 
considered suggestive of severe or pathological dissociation, predicting a diagnosis of Dissociative Identity 
Disorder (DID) with a sensitivity of .74 and specificity of .80, where a cut-off score of 25 predicted the 
diagnosis of DID with sensitivity of .93 and specificity .86 (Carlson & Putnam, 1993). A meta-analysis 
demonstrated the DES-II to have a high test–retest reliability of .78 - .93, an internal reliability (alpha) of .93, 
and a convergent validity of .67 (Thomson & Jacque, 2011). A score of >25 will exclude a potential participant 
from the study. 
The Beck Depression Inventory–II (BDI-II) (Beck et al, 1996) is a self-administered scale that assesses 
symptoms and severity of depression by summing items (Range 0 – 63; mild = 14 - 19; moderate = 20 – 28; 
severe = 29 - 63) a study comparing outpatients diagnosed with mild, moderate, and severe depression, 
respectively, the mean BDI-II total scores were 18 (SD = 8, 99% CI 12-23), 27 (SD = 10, 99% CI 24-29), and 
34 (SD = 10, 99% CI 30-37) (F2.257 = 33.25, p<.001), respectively, demonstrating good validity and no 
overlap between severity categories (Steer et al, 2001). For this study, BDI-II inclusion criteria score will 
include the range from zero to the upper end of the 99% CI found valid for predicting moderate depression (i.e., 
29). Patients over a score of 30 might be entered if PTSD is clearly primary to depression temporally and 
clinically in the opinion of the PI and assessor. 
Combat Trauma Exposure and Pre-Deployment Preparedness 
The Deployment Risk and Resilience Inventory-2 (DRRI-2) (Vogt et al, 2008) is a suite of 17 distinct scales 
that assesses deployment-related risk and resilience factors. The DRRI-2 is the product of a four-year 
Department of Veteran Affairs-sponsored research program funded by two consecutive grants from VA Health 
Services Research and Development Service. The 17 DRRI-2 scales fall into three general categories: 
predeployment factors, deployment factors, and postdeployment factors. These scales assess independent 
factors. For this study we will assess 2 of the scales to assist with adaptive randomization: combat experiences 
(17 items) and preparedness (10 items). Combat experiences assess exposure to objective combat-related 
circumstances on a 6-point Likert response format (1 = Never; 6 = Daily or almost daily), with a possible range 
of 17 to 102; higher scores indicative of more combat experiences. Preparedness assesses the extent to which an 
individual perceives that he/she was prepared for deployment on a 5-point Likert response format (1 = Strongly 
disagree; 5 = Strongly agree), with a possible range of 10 to 50; higher scores indicative of a stronger sense of 

Protocol Rev 3. 4.10.2018 MH 
 
preparedness. 
 
2. Primary Clinical Outcome 
PTSD Severity Score.  Full-scale PTSD scores from the CAPS-5 will be utilized. The scoring is described 
above. CAPS-5 also yields continuous scores for the four symptom clusters, which will also be used for analysis 
of clinical response and association with biomarker change. These clusters are: 
Criterion B (re-experiencing): the sum of the individual severity scores for items 1-5 
Criterion C (avoidance): the sum of items 6 and 7 
Criterion D (negative alterations in cognitions and mood): the sum of items 8-14 
Criterion E (hyperarousal): the sum of items 15-20 
 
3. Secondary Outcome (Startle response assessed by EMG eyeblink during fear conditioning procedure) and 
4.2 Exploratory PPR outcomes (PPR of heart rate, heart rate variability, and skin conductance responses 
assessed at baseline and fear conditioning procedures).  All data will be collected, amplified and digitized by the 
BioSemi recording software (BioSemi B.V, Amsterdam, Netherlands). Data will be exported to Mindware 
software (Mindware Technologies LTD, Gahanna, OH) for data reduction and generation of analyzable 
variables.  
Startle. Startle will be measured by administering a 250 ms airblast with an intensity of 140 p.s.i. directed to 
the larynx as described in similar human fear conditioning studies (Norrholm et al, 2011), recording the 
participants’ electromyographic (EMG) activity during eyeblink muscle contractions. EMG startle eyeblink 
responses will be recorded using two 5mm Ag/AgCl electrodes placed over the orbicularis oculi muscle of the 
left eye. One electrode will be placed directly below the pupil in forward gaze while the other will be placed 
about 1 cm lateral to the first. Both electrodes will be placed as close to the eye as possible while still allowing 
the participant to close his or her eyes comfortably. Impedance between the two electrodes will be measured 
and deemed acceptable if below 10 kΩ. Startle responses will be rectified and integrated for analysis using a 20 
ms time constant. In order to be scored, the onset of the blink response must occur within a window of 20 to 100 
ms after startle probe onset. The blink response must reach peak amplitude within a window of 20 to 150 ms 
following the startle probe. Amplitudes will be recorded as the difference between the peak activity value and 
the baseline level that was present immediately preceding onset of the blink response. Participants who fail to 
reach 1µV amplitudes on more than 50% of probed trials will be considered non-responders and will be 
excluded from further EMG analyses. 
Heart rate. Electrocardiogram (ECG) activity will be recorded throughout the experiment by employing a Lead 
1 electrode placement. Electrode sites will be cleaned with alcohol prep pads to improve contact. 
Skin Conductance. EDA will be recorded by Ag/AgCl electrodes (Unibase gel) attached to the distal phalanx 
of index and middle fingers to measure skin conductance level (SCL) and skin conductance response (SCR).   
General measurement procedure. All PPR measures (secondary and exploratory outcomes) will be obtained 
in a single visit at each timepoint. There are two procedures at each visit, and these total 49 minutes of 
recording time.  We expect the total visit with set-up, prep, and wrap-up to take approximately 70 minutes. This 
includes a 15-minute rest period at the beginning to help diminish anticipatory anxiety. 
Procedure 
Baseline 
5 minutes 
Fear Conditioning 
44 minutes 
Assessed 
Variable(s) 
SC, HRV 
Startle, HR, SCR 
 

Protocol Rev 3. 4.10.2018 MH 
 
Baseline procedure (5 minutes). Tonic measures of SC and HRV will be assessed during a five-minute baseline 
period. Participants will be instructed to sit in a relaxed position but to refrain from moving as much as possible.  
Power spectral density analyses of HRV will be performed with use of a fast Fourier transform based algorithm 
in Matlab. The algorithm will be used to calculate the spectral power of the low frequency (LF) component and 
the high frequency (HF) component of the HRV measure. The frequency range of the LF component is between 
0.04 and 0.15 Hz and is associated with sympathetic activation, while the HF component is between 0.15 and 
0.4 Hz and is associated with parasympathetic activation (Task Force of the European Society of Cardiology the 
North American Society of Pacing Electrophysiology, 1996). We will analyze the LF/HF ratio as a measure of 
cardiac sympathovagal balance.  
Mean and median skin conductance levels will be analyzed during the baseline procedure at pre-treatment, post-
treatment, and follow-up timepoints. Additionally, the frequency of non-specific skin conductance responses 
(NS-SCRs) will be calculated as a measure of sympathetic arousal. NS-SCRs are represented by fluctuations in 
the electrodermal signal of greater than 0.01 microsiemen (µS).  
Fear conditioning procedure (44 minutes). The following methods will allow us to assess fear acquisition, 
within- and between session extinction, and conditioned inhibition (learned safety), as well as participants’ 
awareness of reinforcement contingencies in the experiment. The aversive stimulus (also known as the 
unconditioned stimulus; US) in these studies will be a 250 ms airblast with an intensity of 140 p.s.i. directed to 
the larynx as described in similar human fear conditioning studies (Norrholm et al, 2011). Airblasts will be 
emitted by a compressed air tank connected to polyethylene tubing and controlled by a solenoid switch. 
Conditioned stimuli (CS’s) will be colored shapes presented on a computer monitor. The colored shapes will be 
counterbalanced across subjects. Stimuli will be presented using SuperLab 4.0 for Windows (Cedrus, Inc.) and 
synchronized with psychophysiological data acquisition using a DIO card (Measurements Computing, Inc.). 
The fear conditioning paradigm will consist of 2 experimental sessions at each testing timepoint. Testing will 
occur at baseline, during mid-treatment, post-treatment, and at 6-month follow-up. The fear conditioning 
sessions, described below, include an Acquisition session based on the AX+/BX- design and an Extinction 
session: 
Acquisition (AX+/BX-) Session. Methodology will be similar to those employed in past studies (Jovanovic et 
al, 2009). The session will begin with a Habituation Phase consisting of six acoustic startle probes presented 
alone, referred to as noise alone (NA) trials, to reduce initial startle reactivity. This will be followed by a Pre-
exposure Phase, during which the participants will view the shapes (A, B, and X) but they will not be paired 
with the US. The Acquisition Phase will include 3 blocks with 12 trials (4 AX+, 4 BX-, and 4 NA trials) in each 
block for a total of 36 trials. The Inhibition Testing Phase will consist of a block of 3 NA trials and 3 trials with 
A and B presented together. In the AX+ trials, two shapes of different color will be presented together with a 
“+” between them to encourage elemental processing of the shapes. The shapes will be presented for 6 seconds. 
The startle probe (40 ms burst of white noise at 106 dB) will occur 6 seconds after shape onset; the shape 
presentation will co-terminate with the US 500 ms later. BX and AB trials will also contain two different 
colored shapes, and a startle probe presented 6 seconds after shape onset, but there will be no US in these trials. 
A Re-conditioning block of 12 trials (4 AX+, 4 BX-, and 4 NA) will be presented at the end of the session to 
increase the fear response prior to extinction. Inter-trial intervals will be randomized between 9 and 22 seconds.  
Extinction Session. After a ten-minute rest period following the completion of the Acquisition session or 
AX+/BX-, the same shapes will once again be presented in semi-random order. The extinction phase will 
include 4 blocks of 12 trials (4 AX,4 BX, and 4 NA) in each block for a total of 48 trials. During Extinction, the 
AX trials will no longer be paired with the presentation of the US. The US will not be presented at any time 
during the Extinction phase. Startle probes will still be delivered for 40 ms during shape presentation, 6 seconds 
after shape onset, and will co-terminate with each stimulus. Inter-trial intervals will again be randomized 
between 9 and 22 seconds.   
Under consideration: The above protocol is being used for a current DoD study evaluating the effects of virtual 

Protocol Rev 3. 4.10.2018 MH 
 
reality for conducting Prolonged Exposure. In addition to the above protocol, the DoD study is using a “virtual 
combat zone” at the end of the protocol to assess the change with treatment is psychophysiological response to 
the virtual zone. As more data about the usefulness of this procedure is available, we will consider adding this 
component to the protocol in the current proposal. 
4. Exploratory Outcomes  
Clinical 
PTSD. The PTSD Checklist-Military (PCL-M) (Weathers et al, 1993) (PCL-5 update, November 2013, 
National Center for PTSD) is a 20-item measure designed to assess PTSD symptom severity. Respondents are 
presented with 20 specific symptoms of DSM-5 PTSD and asked to rate ‘how much you have been bothered by 
that problem in the last month’ on a five-point Likert scale, ranging from 0 (not at all) to 4 (extremely). The 
PCL-M has excellent internal consistency in veterans, victims of motor vehicle accidents and sexual assault 
survivors (αs >0.94) and excellent test–retest reliability in veterans (r = 0.96). The PCL-M may be used as a 
diagnostic (dichotomous) or continuous measure. The PCL-5 does not have published data yet, but preliminary 
metric analyses by the National Center for PTSD indicate similar properties (CSP #591 Executive Committee 
communication, P. Schnurr, July 2014). 
Depression. The BDI-II (described above) will be scored as a continuous and ordinal (i.e., mild, moderate, 
severe) variable for analyses. 
Anxiety. The Hopkins Symptom Checklist-25 (HSCL-25) (Derogatis et al, 1974) anxiety scale will be self-
administered to assess symptoms of anxiety. This scale includes 10 items scored on a 4-point ordinal severity 
scale. An item-averaged score >1.75 has been deemed clinically significant in U.S. clinical and community 
populations. Both continuous and dichotomous variables will be used in analyses. 
Somatic Symptoms. The New Mexico Symptom Checklist Somatic Scale (NMSCL-SOM) (Hollifield et al, 
2009) was developed in our previous work on PTSD in refugee populations by combining literature review, 
research team brainstorming and consensus, and in-depth interviews and focus groups to identify physical 
symptoms that are associated with PTSD, and are persistent and distressing in the past year. The NMSCL-SOM 
consists of 39 symptom items drawn from the full scale NMSL-121 administered using a 5-point categorical 
response scale. Hollifield et al. (2009) reported an alpha coefficient of 0.86, and correlations with standard 
measures of distress (a posttraumatic symptom scale and HSCL-25) ranging from 0.63 to 0.75 for the full scale. 
The continuous score will be a secondary outcome in analyses. 
Sleep and Dreaming. The Pittsburg Sleep Quality Index (PSQI) assesses sleep quality during the past month 
based on 7 continuous component scores for sleep quality, latency, duration, efficiency, disturbance, medication 
use and daytime dysfunction that sum to a global score (range 0-21) (Buysse et al, 1989). The PSQI has been 
widely used in sleep and PTSD research. 
Impairment. The Veterans RAND 12-item Health Survey (VR-12), has 12 items that yield physical (PCS) and 
mental (MCS) component summary scores that are normed to the U.S. general population (mean of 50 and SD 
of 10). VR-12 PCS and MCS scores in the Medicare Health Outcome Survey averaged 40 and 50), respectively 
(Selim et al, 2009). More than 2 million VR-12 questionnaires have been administered in the VA for quality 
monitoring purposes. Research studies that have used the VR-12 include randomized clinical trials in the VA 
cooperative studies program, and the nationwide VA Health Study. 
Biological (see description above in secondary outcomes) 
5. Safety Assessment and Other Control Data 
Anger, aggression, and suicidality will be assessed once per week at one of the acupuncture sessions. If a 
subject is identified as having high scores on any of the items, he or she will be further evaluated by the study 
PI (MH) for safety and an action plan will be determined. 

Protocol Rev 3. 4.10.2018 MH 
 
Anger and Aggression. The Aggression Questionnaire (AQ) (Buss et al, 1992) has 29 items and 4 scales 
measuring physical aggression, verbal aggression, anger, and hostility. A total score and an inconsistent 
responding index (lie scale) are also derived. Cronbach’s alpha for the total scale was found to be 0.85 and 
alphas for the scales ranged from 0.72 to 0.85. Test-retest correlations ranged from 0.72 to 0.80. The AQ will be 
fully administered at the primary data collection time points. To evaluate safety, ten items (1, 2, 5, 8, 11, 13, 18, 
23, 25, 28) will be administered weekly as described above. 
Suicidality. The Beck Depression Inventory–II (BDI-II) (Beck et al, 1996) items 9 (suicidality), 11 (agitation), 
and 17 (irritability), will be administered once per week as described. A score of 2 or 3 on any item will prompt 
further evaluation. Item 9 has been shown to be moderately correlated to the full scale Beck Scale for Suicide 
Ideation (Beck et al, 1988). 
Satisfaction with Care. The Opinions about Care and Provider Scale is adapted from a scale developed by our 
research team for an NIH-sponsored study. Ten items assess opinions about care and represent satisfaction with 
care. Five items are designed to assess if the participant was taught specific skills. 
Intercurrent Health Resource Use Inventory. This will be administered at baseline, end-of-treatment, and 6-
month post treatment to help account for other non-study treatment effects. 
 
6. Treatment Fidelity and Expectancy as Potential Moderators to Outcome 
Treatment Fidelity. A Therapist Adherence Scale will be developed in the first 3 study months. It will be like 
one in the Appendix which was developed for computer assisted CBT 
Treatment Expectancy will be assessed with The Credibility Rating Scale (Borkovec, 1972), which has been 
utilized in many clinical trials including other studies comparing interventions to placebo’s in general. 
Treatment Fidelity and Subject Expectancy. Assuring treatment fidelity (clinician) is important in clinical 
trials. This may be accomplished by various methods, dependent on trial design, and often involves standard 
training, random checks by live or taped observation, and ongoing training to promote reliability. With one 
practitioner, accuracy and consistency is required, but of course there is no need for inter-therapist reliability. 
First, the study acupuncturist hired will be well-trained, research experienced, and further trained on study 
protocol by Dr’s. Hollifield and Hsiao. At least five volunteer patients using each ACU and MIN will be treated 
and observed; landmarks, needle insertion and manipulation, electrical stimulation, and needle removal will be 
judged and discussed for each case. Second, non-specific elements of the intervention, such as instructions for 
treatment preparation, and interactions during treatment will be reliably delivered by using clinical scripts 
adapted from our first study. Third, all treatment sessions will be videotaped. The first 5 and a random selection 
of 15% (18 total cases) thereafter chosen by a computer randomizer will be scored by study assessor supervised 
by Dr. Reist using the Fidelity Assessment Rating Form adapted for this study. Dr’s. Hollifield and Hsiao will 
provide feedback to the acupuncturist about improvement. We will use scores to explore score effects by group. 
It is important to assess effects of treatment expectancy on outcomes. We do not want to encourage subject 
learning about type of intervention, so will not assess expectancy after each session. Rather, we will assess 
treatment credibility (Borkovec, 1972) as has been done in previous acupuncture studies before session 1 and 
after sessions 2 and 24, and explore effects of expectancy by group and total sample on outcome. 
Demographic and Other Data. A demographic and other data form will be developed for this study to assess 
important information for matching and data analyses: age, gender, ethnicity, combat history, medical history, 
medications, potential head injury, exposures to toxic chemicals, and current treatment. 
 
 
 

Protocol Rev 3. 4.10.2018 MH 
 
Human Subjects Detail 
 
Human Subjects Involvement and Characteristics:  This study will utilize a longitudinal randomized design 
to evaluate the efficacy of 12-week manualized verum acupuncture (ACU) for PTSD in combat Veterans. The 
primary outcome will be the pre-to post-treatment change in PTSD symptom severity. The secondary outcome 
will be a peripheral physiological response (PPR) of startle response to a stimulus. Exploratory outcomes will 
be other PPR indices (biological) and clinical conditions that are associated with PTSD.  Potential subjects will 
be recruited from the Long Beach Veterans Affairs Healthcare System (LBVA) and associated Veteran 
organizations. We will randomize 90 subjects into the two study groups of 45 each: subjects will be randomized 
to either: (1) verum acupuncture (ACU), or (2) placebo minimal needling (MIN). 
Potential risks: The general risks are primarily psychological.  Being asked to recall adverse life events or 
distressing symptoms in the diagnostic interview may compound the distressing nature of PTSD.  However, 
interviews with survivors of torture and related trauma have found that testimony about  traumatic experiences 
can be therapeutic (Cienfuegos and Monelli 1983; Agger and Jensen 1990; Thompson and McGorry 1995).  
There is evidence that trauma disclosure is helpful physically and psychologically over time, although in the 
short-term symptoms of depression may increase (Pennebaker and Susman 1988).  The likelihood of the study 
worsening PTSD is small, since by the nature of the disorder, those who have PTSD will already be 
“experiencing” their trauma in a variety of ways, and all subjects will be provided with one EBT, the 
medication paroxetine.  Study personnel need to be attentive to population and individual responses. 
The physical risks include those from acupuncture, which includes minor bruising, hematoma and bleeding, 
fainting or nausea.  There is a less than 1 in 10,000 risk of pheumothorax, and the reports of this are when the 
procedure was conducted by inexperienced clinicians.  There is no reported risk from the psychophysiological 
assessment, although the stimulus (an air blast to the neck) is meant to be aversive, and participants have in 
other studies not wanted to return for testing. 
Research risk: PTSD is a chronic illness that creates vulnerability and can lead to potential exploitation of 
subjects.  The study includes interviews and questionnaires about PTSD symptoms and potentially traumatic 
combat experiences, as well as about other psychiatric symptoms and life events.  In many studies involving the 
collection of information for gaining knowledge (e.g., biological markers), participants may not receive 
intervention for the condition under study.  In this study, 45 subjects with PTSD will receive ACU, an 
intervention supported by current VA/DOD treatment guidelines for PTSD.  Forty-seven will receive MIN, a 
placebo intervention. There is risk that their PTSD will go untreated, though study protocol will allow evidence-
based medication if they are on them at a stable dose for >8 weeks. There is the risk that any participant will not 
improve but will either continue to have similar or higher levels of distress and symptoms. 
Audio-Video Taping: Subjects will be asked to sign an informed consent to be taped. This consent will detail 
the use of the tapes (that they will be reviewed for provider treatment review), and that the tapes will be erased 
after the scoring for treatment fidelity is completed 
There is a risk of non-effectiveness.  This is more likely to be true for the MIN subjects. 
 
Sources of Materials 
Training materials. Any training materials will be available for study staff to use during the project. These 
materials are products of the project and will be kept in locked offices at the LBVA research offices throughout 
and after the end of the project. 
Participant rosters. The electronic and hard copy rosters with full identifiers (participant names, addresses, and 
phone numbers) that can be linked to study and treatment ID numbers will be kept in locked file cabinets in 
research offices that are locked after hours at the LBVA. The electronic files will be password protected. At the 
end of the project only two copies of the research rosters will be kept in separate locked cabinets at the LBVA 

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research offices. Original rosters that connect ID numbers with participant identifiers will be destroyed at the 
end of the project. Electronic and hard copy rosters after the end of the project will be thus de-identified. 
Data. Scores and data from psychological and physiological testing will be recorded and utilized solely for 
research purposes. All data will be entered into an electronic database at LBVA as the project progresses, and 
similar backup procedures will be employed. All hard copies of data will be marked only with a Study 
Identification number (SID#) and will be kept in a locked file cabinet in a space that is separate from participant 
rosters. After the hard coy questionnaire data is entered into the electronic database all original hard copies will 
be kept in locked research offices at LBVA. Final biological data that is analyzed or reviewed by any of our 
consultants at other institutions will only be identifiable by SID # and a date of collection number. These data 
will be sent between institutions by a passcode protected and encrypted email. Data are backed up each day on 
the main server at the LBVA. 
Data Management Plan. The study data analyst (DA) will develop spreadsheets for each assessment in EXCEL 
under the supervision of the PI and the statistical consultants. The physiological data will be formatted for entry 
into ASCI files, which can be transferred to either EXCEL or MATLAB sources.  The DA will enter and double 
check all data into respective spreadsheets as the data are collected.  Once data entry is completed and merged 
into the primary database, transfer into SPSS or SAS files will be conducted and initial data runs will be 
performed to investigate data integrity. Once data integrity is determined, an original set of data files will be 
stored as “original” in case other iterations are harmed, altered, or lost. All electronic data files will be passcode 
protected, and only SID numbers and not other identifiers will be on each spreadsheet. 
Compensation Plan. Our research team has consulted with participants and professional advisors to determine 
compensation for participants in this project. The amounts allocated ($25 for initial assessment, $150 for all 
biological assessments, $25 for follow-up assessment, and $50 for participating in the clinical trial) were 
thought to be fair given the level of participation and the potential benefit of intervention, and are intended to 
not be exploitative either from being insufficient for the time and effort spent, or as being coercive by being too 
large a sum. 
 
2. Adequacy of Protection from Risk 
 
Recruitment and Informed Consent 
The methods of recruitment, informed consent, interviewing, and other assessment is intended to be protective 
for the participants, as they are potentially vulnerable to exploitation and harm given their medical/psychiatric 
status.  We are attentive to ethical protections by: 1) following guidelines for ethically sound research, and 2) by 
having the capacity at LBVA to review research forms and treatment protocols from both a scientific and 
ethical perspective.  Finally, we will encourage participants to ask questions and include family and friends in 
the informed consent decision process. 
The process of obtaining informed consent is conducted at the Program for Traumatic Stress or a designated 
research office located at LBVA.  Only authorized and properly trained study personnel by the PI are permitted 
to participate in the actual consent process.  Potentials subjects will be asked by research staff if he is interested 
in participating in the study.  If he is interested, research staff will conduct education and ascertain if  he wishes 
to participate.  If the potential subject agrees to participate, the subject will be asked to provide informed 
consent.   
Potential subjects will be asked if s/he can understand the consent form by reading the first paragraph.  
Qualified study personnel will then fully explain each section of the consent form in detail and will ask the 
potential subject to follow-along with another copy of the consent form.  All potential subjects will be properly 
informed about the purpose of the study, study procedures, and the potential risks and benefits of being a 
participant.  Each potential subject will affirm his or her understanding of each section prior to moving on to the 
next, and then will be given a copy of the consent form to also read at his leisure.  The qualified research 

Protocol Rev 3. 4.10.2018 MH 
 
personnel will then ask the subject a number of open-ended questions about his level of understanding to ensure 
he has processed the information.   
Once all questions have been asked and answered to each party’s satisfaction, the consent form will be signed 
by the potential research subject and the qualified study personnel.  If a potential subject wishes to think about 
participation, he will be encouraged to take the consent home, think about it, and discuss it with anyone whom 
he has a close personal relationship with to assist in making a decision.  It will always be stressed that 
participation is fully voluntary and does not compromise care provided by the LBVA and the Program for 
Traumatic Stress.  If the potential subject agrees to participate in the study, the PM will obtain written informed 
consent; the subject will be given a signed and dated copy of the consent form for his record.  Once informed 
consent has been obtained, a screening for inclusion and exclusion criteria will be conducted to confirm 
eligibility for the study.  The PM, who obtained informed consent, will document into the subject’s electronic 
file in Computerized Patient Record System (CPRS) that informed consent was obtained. 
 
Protections Against Risk 
All research team members, including investigators, consultants, contractors and staff will be asked to sign a 
statement that details their conduct regarding participant confidentiality. This statement details consequences to 
team members for breach of confidentiality. 
Our research staff is or will be trained to be open to participant questions and concerns. The participants will be 
encouraged to have an ongoing discussion and dialogue with the clinicians and staff. It will be made clear to 
each participant in the informed consent process and beyond that participation is voluntary, and that he may 
withdraw at any time without adverse consequences to his usual health care. 
We recognize the variability of individual responses to answering questionnaires and interview questions 
related to PTSD, other life events, symptoms, and current health and social status. Team members will be 
sensitive and helpful to any individual participant who is distressed, whether or not the distress is from a 
research effect. The PM at LBVA is very experienced with and will field all calls and inquiries from 
participants about urgent treatment needs.  If it is PTSD or study related, the PM will immediately troubleshoot 
the potential problem with the PI.  If it is emergent, the PM will help the participant make a plan for a visit, 
which may include calling emergency transportation. 
Adverse effects are extremely rare when acupuncture is performed in a professional setting by a fully trained 
and certified acupuncturist.  Four out of the 5 deaths that have been associated with acupuncture in the literature 
were not equivocally due to acupuncture or were either self administered or administered by an untrained 
person.  Possibilities of cross-infection will be avoided by using disposable needles and following clean-needle 
technique procedures.  Other adverse effects will be avoided by using a fully trained and licensed acupuncturist 
who will practice in a professional setting.  
The risk of non-effectiveness is mitigated by subjects being allowed to be taking medications for symptoms of 
PTSD and related conditions. Participants will be seen twice per week for protocol, and will be assessed each 
visit for aggression and suicidal ideation. Rules for withdrawal from study because of symptoms and/or 
potential danger to self or others will be part of protocol. 
The video tapes will be destroyed after they have been reviewed for treatment fidelity. 
Any adverse events will be documented and reported to proper authority.  All research staff has been or will be 
trained in and abide by ethical research methods and good clinical practices.    
 
3. Potential Benefits 
 
There may be no direct benefit for a person to participate in this study, although we hypothesize benefit to 
subjects in the ACU group.  The risks are minimal but present.  For this study, an emphasis on informed consent 

Protocol Rev 3. 4.10.2018 MH 
 
and safety is important.  Results from this study are intended to provide a better understanding of the effects of 
acupuncture on PTSD and on peripheral psychophysiology. This information may enhance knowledge of and 
shape the treatment for PTSD which may potentially help thousands of veterans suffering from this illness. 
 
4. Importance of Knowledge to be Gained 
 
This study will improve knowledge about the use of acupuncture for PTSD, and will inform the field and policy 
makers about how acupuncture may be useful treatment for symptoms and biological functioning. Research 
evaluating how abnormal biological function in PTSD might be reversible with intervention is rare, and this 
study will help us understand what is reversible and what is not. This may improve our knowledge about 
mechanisms of treatment, and perhaps provide insight into risk factors. This will hopefully provide potential 
biological targets for further study. 
 
5. Data and Safety Monitoring 
 
Subjects will be given a sequential ID number that does not identify their PTSD status or their group 
assignment. Electronic and hard copy rosters with full identifiers (participant names, addresses, and phone 
numbers) that can be linked to study numbers will be kept in locked file cabinets in research offices that are 
locked after hours at LBVA.  The electronic files will be password protected.  At the end of the project, original 
rosters that connect ID numbers with participant identifiers will be destroyed.  
In past studies in other settings we have constructed an internal Data and Safety Monitoring Committee or 
Board depending on the trial. We recognize and are pleased to know that, with funding via a Merit Review from 
CSR&D, we are eligible to use the services of the Centralized Data Monitoring Committee (DMC), and we are 
pleased that this study will have the availability of oversight by a CSR&D Centralized DMC panel. 
The study protocol and requests for research review are pending submission to the Institutional Review Board at 
the VA Long Beach Healthcare System. The IRB at the VA Long Beach meets twice a month, and so the 
protocol will be able to be reviewed and appropriately approved within the first three months after funding. 
To ensure adequate subject recruitment and enrollment, we will utilize recruitment flyers and approach subjects 
and clinicians at the Program for Traumatic Stress, in other mental health clinics, at Vet Centers and CBOC’s to 
introduce the project and ask clinicians to refer any patients that may be interested in the study. We have 
developed this system of recruitment in the context of a current clinical trial. 
 
 

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