Conditions: PTSD
Keywords: Minocycline PTSD
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 10
Healthy volunteers: no

Brief summary:
The study will evaluate the safety and efficacy of adjunctive minocycline treatment in veterans with PTSD.

Detailed description:
This is a 12-week, open-label pilot study in which adjunctive minocycline will be administered to approximately 15 veterans diagnosed with PTSD.

Arms:
arm 1: Minocycline 100 mg/day 1 to 7 and 200 mg/day 8 to end of week 12

Interventions: intervention 1: Minocycline
Intervention descriptions: intervention 1: Minocycline capsule

Protocol document:
Prot_SAP_000.pdf: 
Study Title  
 
Minocycline for Treatment of Posttraumatic 
Stress Disorder in Veterans 
NCT Number 
NCT03340350 
Document Description 
Study Protocol 
Document Date 
January 10, 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


1 
 
Study Title: Minocycline for Treatment of Posttraumatic Stress Disorder in Veterans 
Principal Investigator: Sriram Ramaswamy, MD 
Background:  
 
Posttraumatic Stress Disorder (PTSD) is a debilitating disorder characterized by re-
experiencing aspects of the original trauma, avoidance and numbing of trauma 
reminders, and general hyperarousal. Lifetime prevalence of PTSD in community 
samples is around 6.8%, Operation Enduring Freedom (OEF)/Operation Iraqi Freedom 
(OIF) veterans around 12.5%, and as high as 30% among Vietnam veterans.1,2 
According to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition 
(DSM-IV), one must experience a specific set of symptoms for at least one month 
following exposure to a traumatic event in order to meet criteria for PTSD.  
 
It has been proposed that cumulative stress may play a significant role in the 
development of PTSD.3 There is also evidence that impairments in higher-order 
cognitive abilities (i.e., executive functions) may contribute to symptoms of PTSD.4,5 
One possibility is that chronic inflammation may contribute to PTSD symptoms. Several 
studies have reported elevated levels of pro-inflammatory cytokines such as C-reactive 
protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNFα) in patients 
with PTSD. Groer et al. studied levels of inflammation in active duty military personnel 
and found that elevated CRP was associated with depression and PTSD symptoms.6 
Another study that compared two groups of combat exposed veterans, one group with 
PTSD and one without, found that combat-related PTSD in males was associated with 
higher levels of pro-inflammatory cytokines, even after accounting for depression.7 It 
has been proposed that elevated inflammatory cytokine activity in individuals with PTSD 
may result from inadequate regulation by the stress hormone cortisol.8 Low levels of 
cortisol promote excessive catecholamine production, which can lead to enhanced 
sympathetic activity. Enhanced sympathetic activity can amplify traumatic memories 
and lead to expression of PTSD symptoms.9 These findings indicate that increased 
inflammation due to disruption of the HPA axis and altered immune system feedback 
may play a role in the development of PTSD.10 Furthermore, in a recent prospective 
study, Eraly et al. examined levels of CRP in active-duty military personnel 3-6 months 
after returning from deployment. They found that those with elevated pre-deployment 
levels of CRP were more likely to develop PTSD, suggesting that individuals with higher 
inflammation may be more likely to develop PTSD.11 
 
Such findings raise the possibility that inflammation may serve as a potential target for 
treatment in individuals with PTSD. Minocycline is a broad-spectrum tetracycline 
antibiotic with anti-inflammatory and neuroprotective properties and has been shown to 


2 
 
reduce levels of pro-inflammatory cytokines. Several studies have reported evidence 
indicating that minocycline may help in treating symptoms of psychiatric disorders such 
as schizophrenia12-17 and depression.18,19 Such treatments might also prove beneficial 
in treating health conditions associated with chronic inflammation that are commonly 
comorbid with PTSD, such as chronic pain, arthritis, diabetes, and cardiovascular 
disease.8,20 A study using an animal model of PTSD found a reduction in stress-related 
behaviors as well as decreased levels of inflammatory cytokines, suggesting that the 
anti-inflammatory effects of minocycline may help to improve symptoms of PTSD.21  In 
addition, a recent study of fear conditioning in humans found attenuated fear memory in 
individuals administered the tetracycline antibiotic doxycycline, suggesting that such 
medications may help to improve symptoms of PTSD.22 However, no studies to date 
have investigated the efficacy of minocycline treatment in veterans with PTSD. 
 
Significance:  
The Veterans Health Administration has a growing population of veterans exposed to 
combat during their military service, and there is a clear need to identify more effective 
forms of treatment for PTSD. Understanding the clinical phenomenology, risk factors 
and potential biomarkers of this condition could pave the way for better screening 
methods and treatment interventions for clinicians.  
 
Study Aim: 
The specific aim of this pilot study is to assess the safety and efficacy of adjunctive 
minocycline treatment in veterans with PTSD. 
 
Hypothesis:  
We hypothesize that treatment with adjunctive minocycline will be associated with 
reduced inflammation (as indexed by levels of inflammatory cytokines) and reduced 
severity of PTSD and mood symptoms. 
 
Study Design:  
A 12-week, open-label pilot study in which adjunctive minocycline will be administered 
to approximately 15 subjects diagnosed with PTSD. 
 
Participants: 
Recruitment: Participants will be recruited from the pool of patients presenting to the 
Omaha VA Medical Center. 
    


3 
 
Inclusion Criteria: 
1. Veterans between the ages of 19 and 65 who meet DSM-5 criteria for chronic PTSD. 
2. Patients who have been taking an adequate dose of SSRI or SNRI medication, 
bupropion, or mirtazapine for a minimum of 8 weeks at the time of study entry. 
3. PTSD Checklist for DSM-5 (PCL-5) score of > 33 at the Screening Visit. Eligible 
persons will be allowed to have other symptoms that are commonly comorbid with 
PTSD (e.g., anxiety, somatic symptoms). This strategy will provide a feasible and 
generalizable sample of those with chronic PTSD.  
 
Exclusion Criteria: 
1. Patients with a concurrent DSM-5 diagnosis in any of the following categories: 
1.1. Major Neurocognitive Disorder (NCD) 
1.2. Lifetime Schizophrenia and other Psychotic Disorders 
1.3. Lifetime Bipolar Disorder  
1.4. Alcohol Dependence or Abuse in 3 months prior to the Screening Visit 
1.5. Any other Substance Dependence or Abuse (excluding nicotine) in 12 months 
prior to the Screening Visit 
1.6. Any other concurrent Axis I Disorder (including Major Depressive Disorder) must 
be secondary to the primary diagnosis of PTSD. 
2. Chronic pain levels requiring use of any opiate medications with the exception of 
Tramadol. Patients are allowed the use of Tramadol at 25-50 mg per day dosing. 
3. Any condition or disorder that may cause neuropsychiatric sequelae (e.g., 
Parkinson’s disease, stroke, seizures, or TBI).  
4. Past chronic PTSD, meaning PTSD that preceded the incident traumatic event 
responsible for the current PTSD. Other traumatic life events will not be exclusionary 
unless they resulted in previous PTSD. 
5. Patients with a history of intolerance or hypersensitivity to minocycline or other 
tetracycline antibiotics, or prior tetracycline use 2 months prior to the Screening Visit. 
6. Concomitant treatment with penicillin or other antibiotics, or treatment with antibiotics 
for greater than 7 days in the past month.  
7. Use of aspirin, non-steroidal anti-inflammatory agents (NSAIDs) or COX-2 inhibitors 
for < 6 months prior to study entry or dose changes after study entry. Limited as-
needed use is permitted prior to study entry but not during the study. 
8. Use of statins will not be permitted during the study as they have been shown to 
reduce levels of pro-inflammatory cytokines. 
9. Use of concomitant anti-coagulant drugs (except low-dose aspirin) as minocycline 
has been shown to depress plasma prothrombin activity. 
10. Any degree of hepatic or renal failure that in the Investigator’s judgement would 
pose a safety risk for treatment with minocycline. There are no dosage adjustments 
recommended in the manufacturer’s labeling in hepatic insufficiency. In case of renal 


4 
 
impairment the following PDR guidelines will be followed: CrCl ≥80 mL/minute: No 
dosage adjustment necessary; CrCl <80 mL/minute: Do not exceed 200 mg daily. 
11. Conditions which may be negatively affected by minocycline treatment, such as 
active inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease). 
12. A history of C. difficile colitis.  
13. Patients who based on history or mental status examination have a significant risk of 
committing suicide, or who are homicidal or violent and who are in the Investigator’s 
opinion in significant imminent risk of hurting others. 
14. Patients who have a medical condition that, in the Investigator’s opinion, would 
expose them to an increased risk of a significant adverse event or interfere with 
assessments of safety and efficacy during the course of the trial. 
15. Women who are pregnant or plan to become pregnant during the study. All women 
of childbearing potential must have a negative urine pregnancy test at the Screening 
Visit and throughout the study. Sexually active women participating in the study must 
use a medically acceptable form of contraception. 
16. Patients with a current known infection or who are acutely ill. 
17. Patients with an autoimmune disease (i.e., Lupus, Rheumatoid Arthritis). 
18. Immunocompromised patients (i.e., HIV). 
19. Patients with thyroid disorders unless euthyroid at screening. 
20. Patients with cancer not in remission. 
21. Patients with CVD, such as myocardial infarction and arrhythmias. 
22. Patients with diabetes.  
23. History of significant esophagitis. 
24. Patients who plan to initiate or terminate any psychotropic medication during the 
study. Patients taking any psychotropic medication should be on a stable dose for at 
least 6 weeks prior to the Screening Visit (except for the SSRI, SNRI or mirtazapine 
used to treat their PTSD) AND agree not to discontinue or otherwise alter treatment 
during the study. 
25. Patients who plan to initiate or terminate any form of psychotherapy or behavior 
therapy during the study with the exception of PTSD Orientation Group. Subjects 
may be in supportive psychotherapy if it was initiated at least three months prior to 
the Screening Visit AND subject agrees not to discontinue or otherwise alter therapy 
during the study. Subjects receiving evidence-based psychotherapies such as 
Prolonged Exposure or Cognitive Processing Therapy will be excluded. 
26. Patients who are unable to speak, read, and understand English or are judged by 
the Investigator to be unable or unlikely to follow the study protocol and complete all 
scheduled visits. 
 
 


5 
 
Study Procedures: 
 
The schedule of all study visits and procedures is summarized below and in Table 1. 
 
Screening Visit (Visit 1): 
After providing informed consent, patients will be screened for participation in the study. 
The Mini-International Neuropsychiatric Interview (MINI) will be used to screen for 
comorbid psychiatric disorders. The PTSD Checklist for DSM-5 (PCL-5) will be used to 
confirm diagnosis of PTSD. Depression symptoms will be assessed using the Beck 
Depression Inventory-II (BDI-II). Medical history, physical exam, vital signs, and review 
of concomitant medications will also be completed. 
 
Blood and urine samples will be obtained and tested by the Omaha VA Outpatient Lab. 
Laboratory tests will include complete blood count (CBC), comprehensive metabolic 
panel (CMP), routine urinalysis, urine pregnancy test (if applicable), C-reactive protein 
(CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNFα). Based on previous 
research, we anticipate that levels of pro-inflammatory cytokines (CRP, IL-6, and TNFα) 
may be elevated. However, as patients with non-elevated cytokine levels at screening 
may still exhibit significant change over the course of the study and provide useful data, 
no minimum cutoff level for cytokines will be used in this study. 
 
Baseline Visit (Visit 2): 
PTSD symptoms will be assessed using the Clinician-Administered PTSD Scale for 
DSM-5 (CAPS-5). The CAPS is a 30-item structured interview that corresponds to the 
DSM criteria for PTSD. It is considered by many to the gold standard in the diagnosis 
and assessment of PTSD. We will use the CAPS to assess past month (current) PTSD. 
The Clinical Global Impressions (CGI) Scale will be administered to assess overall 
severity of symptoms, and vital signs will also be obtained. As previous research 
indicates that executive dysfunction may contribute to PTSD symptoms,4,5 we will 
assess executive functioning using two measures: the Trail Making Test (TMT) and 
Controlled Oral Word Association (COWA) Test. The TMT is a measure of visual 
attention and task switching, while the COWA is a measure of verbal fluency. 
Concomitant medications will be reviewed and drug dispensing will occur at this visit. 
 
Follow-up Visits (Visits 3-6):  
Visit 3 will be a telephone contact to monitor dose increase from 100mg/day to 
200mg/day. Visits 4-6 will be clinic visits to include the following procedures: vital signs, 
adverse event evaluation, drug dispensing/accountability/adjustment, and review of 


6 
 
concomitant medications. The CGI will be administered to assess overall severity and 
improvement in symptoms. 
 
End of Study (Visit 7): 
The end of study visit will include administration of the CAPS, BDI-II, CGI, TMT, and 
COWA scales, as well as physical exam, vital signs, and laboratory evaluation 
(including measurement of CRP, IL-6, and TNFα). Adverse event evaluation, drug 
accountability, and review of concomitant medications will also be completed at this 
visit. 
 
Safety Follow-up (Visit 8): 
This visit will be conducted only for patients who have ongoing adverse event(s). The 
following procedures will be completed at this visit: CGI, vital signs, adverse event 
evaluation, and review of concomitant medications. 
 
Study Medication and Dosing Regimen: 
This is a 12-week, open-label study in which minocycline will be administered to 
veterans with PTSD. Dosing will be titrated to reduce potential side effects that may be 
experienced when starting minocycline. The titration schedule is as follows: 100 mg/day 
1 to 7, 200 mg/day 8 to end of week 12. 
 
During the course of the study patients will be supplied with 100 mg minocycline 
capsules. Study medication will be administered as a single daily dose (100 mg 
total/day 1 to 7) or twice daily dose (200 mg total/day 8 to end of week 12). Subjects will 
be instructed to take study mediation with a full glass of water and to not lie down for at 
least 30 minutes after taking it. Also, patients taking antacids containing aluminum, 
calcium, or magnesium and preparations containing iron will be instructed to take these 
at least 2 hours before or after minocycline administration.  
 
The Investigator may adjust the dosing regimen during the course of the study based on 
tolerance to the study medication. The maximum dose permitted for minocycline will be 
200 mg per day. Upon the Investigator’s determination of the dosage regimen for each 
subject, the study medication will be dispensed in an amount sufficient to cover the 
window between the study visits plus at least 3 extra days during the first month of the 
trial, and 7 days over the second and third months.  
 
Treatment compliance will be monitored by counts of returned medication. Records of 
concomitant medications will be taken at each study visit as well as reports of adverse 
events. 


7 
 
Efficacy Evaluation: 
The primary efficacy measures will be (1) change in CAPS total scores from baseline to 
end of study, and (2) change in levels of the inflammatory cytokines CRP, IL-6, and 
TNF-α from screening to end of study. Secondary measures of efficacy will include 
change in BDI-II, CGI, TMT, and COWA scores from baseline to end of study. 
 
Statistical Analysis: 
Statistical analyses will include t-tests (or a nonparametric equivalent) for comparison of 
scores on CAPS, BDI-II, CGI, TMT, and COWA from baseline to end of study and 
change in inflammatory cytokine levels from screening to end of study. Correlational 
analyses will be used when appropriate to determine the degree of association among 
variables. Further analyses will be conducted to examine the effects of other factors on 
the primary measures (e.g., medical and psychiatric history, concurrent psychiatric 
treatment). SPSS software will be used for statistical analyses. 
 
Safety Evaluation and Monitoring: 
Safety will be monitored by reports of adverse events at all treatment visits throughout 
all phases of the study. This may include any clinically significant changes in vital signs 
(blood pressure, pulse, and weight), physical examinations, laboratory evaluations 
(blood chemistry, hematology, and urinalysis) and recording of concomitant treatment. 
In cases of adverse effects of minocycline treatment, trial medication will be stopped for 
five days and then recommenced. Participants will be contacted following 
recommencement to determine if adverse effects have returned. 
 
Treatment compliance will be monitored by counts of returned medication, and patients 
will be counseled if they do not adhere, or if they are thought to be at risk for not 
adhering to the medication regimen. 
 
A Data Safety Monitoring Committee (DSMC) will be utilized to ensure patient safety 
and will consist of expert clinicians in the disease area. Drs. Robert Langenfeld and 
Angelo Zieno, Staff Psychiatrists will review safety data. The DSMC will have access to 
any and all data to assess the safety of the subjects. Adverse event data will be tallied 
and maintained for the DSMC to review. Following each data review, the DSMC will 
make recommendations regarding the conduct of the study, including continuing the 
study without modifications, to terminate or to modify the study design for safety 
reasons.  
The following will be considered as decision rules to discontinue the subject’s 
participation in the study: If the subject develops symptoms requiring treatment with 


8 
 
antibiotics or other forms of treatment not permitted during the course of the study (see 
Exclusion Criteria). If the subject experiences a serious adverse event. If the subject 
develops suicidal or homicidal thoughts. If the subject misses two or more consecutive 
study visits in a row. If the subject takes less than 80% of the study medication as 
prescribed. 
 
Human Subject Protection and Confidentiality: 
During screening, we anticipate some subjects to endorse suicidal thoughts either 
current or past. We propose to manage suicide risk by a systematic and careful 
assessment of suicidality. Subjects will be assessed at screening using the MINI 
Suicidality Module. This instrument provides information regarding past history of 
suicidal ideation and attempts as well as information about recent and current suicidal 
thinking, plans and attempts. Participants with a past history of attempt(s) and/or current 
serious ideation will trigger a more detailed review of their risk by the PI. The disposition 
of subjects with serious symptoms will follow standard clinical care protocol. Such 
subjects will not proceed in the study. 
 
Patients with diagnosis of major mental disorders (e.g., bipolar disorder, psychotic 
disorders) that were previously undiagnosed will be referred to the PCP for further 
management and will be offered a same day walk-in appointment in the Mental Health 
Clinic. 
 
Utmost care will be taken to ensure subjects’ psychological well-being and minimize 
discomfort during administration of protocol assessments. Psychological instruments 
will be administered by team members trained and experienced in dealing with PTSD. 
In the event a subject experiences worsening mood, anxiety or sleep problems following 
the visits, they will be provided an opportunity for debriefing and may exit the study if 
they require treatments not permitted during the study. 
 
To protect privacy and confidentiality, we used only coded data without patient names 
or identifiers. All working papers will be stored in a secure area and will be shredded 
when they are no longer useful. An electronic database will be created for storage of the 
data. Data from all sources will be entered into an Excel spreadsheet maintained in a 
secure, limited access folder on the secure VA NWI server via secure VA computers 
directly on site. De-identified data in the Excel spreadsheet eventually would be 
converted into a SPSS database for statistical analysis. No PHI or other identifiable data 
will leave the VA secure environments, physical or electronic. Access to the records will 
be limited to the study team. 
 


9 
 
All participants will be asked to sign a HIPAA authorization to allow for access and use 
of protected health information (PHI). This authorization will expire at the end of the 
study. Protected health information (PHI) to be used or collected will include information 
from patients' VA Health Records (e.g., diagnoses, medications) and specific 
information concerning alcohol and drug abuse, HIV, demographics, and 
questionnaires. This information may be disclosed to entities outside the VA, including 
other federal agencies required to monitor or oversee research (e.g., the Food and Drug  
Administration (FDA), Government Accounting Office (GAO), Office of Human Research 
Protection (OHRP)), Nebraska Educational Biomedical Research Association (NEBRA), 
and a VA contractor for purposes of accreditation. 
 
Resources:  
No resources beyond what is already available in terms of staff and equipment will be 
necessary to conduct this project. 
 
Source of Funding:  
NEBRA - Nebraska Educational Biomedical Research Association, Creighton University 
 
References: 
1. Kulka RA, Schlenger WE, Fairbank JA, et al: National Vietnam Veterans 
Readjustment Study (NVVRS): Description, Current Status, and Initial PTSD 
Prevalence Estimates. Research Triangle Park, NC: Research Triangle Institute; 
1988. 
2. Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat 
duty in Iraq and Afghanistan, mental health problems, and barriers to care. N 
Engl J Med. 2004; 351(1):13-22. 
3. McFarlane AC. The long-term costs of traumatic stress: intertwined physical and 
psychological consequences. World Psychiatry. 2010; 9(1):3-10. 
4. Mota N, Tsai J, Kirwin PD, et al: Late-life exacerbation of PTSD symptoms in US 
veterans: results from the National Health and Resilience in Veterans Study. J 
Clin Psychiatry 2016; 77(3):348-354. 
5. Aupperle RL, Melrose AJ, Stein MB, Paulus MP. Executive function and PTSD: 
disengaging from trauma. Neuropharmacology. 2012;62(2):686-694. 
6. Groer MW, Kane B, Williams SN, Duffy A. Relationship of PTSD symptoms with 
combat exposure, stress, and inflammation in American soldiers. Biol Res Nurs. 
2015; 17(3):303-310. 
7. Lindqvist D, Wolkowitz OM, Mellon S, et al: Proinflammatory milieu in combat-
related PTSD is independent of depression and early life stress. Brain Behav 
Immun. 2014; 42:81-88. 
8. Gill JM, Saligan L, Woods S, Page G. PTSD is associated with an excess of 
inflammatory immune activities. Perspect Psychiatr Care. 2009; 45:262-277. 


10 
 
9. Pace TW, Heim CM: A short review on the psychoneuroimmunology of 
posttraumatic stress disorder: from risk factors to medical comorbidities. Brain 
Behav Immun. 2011; 25(1):6-13. 
10. Raison CL., Miller AH. When not enough is too much: the role of insufficient 
glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J 
Psychiatry. 2003; 160:1554-1565. 
11. Eraly SA, Nievergelt CM, Maihofer AX, et al: Assessment of plasma C-reactive 
protein as a biomarker of posttraumatic stress disorder risk. JAMA Psychiatry. 
2014; 71(4):423-431. 
12. Levkovitz Y, Mendlovich S, Riwkes S, et al: A double-blind, randomized study of 
minocycline for the treatment of negative and cognitive symptoms in early-phase 
schizophrenia. J Clin Psychiatry. 2010; 71(2):138-149.  
13. Miyaoka T, Yasukawa R, Yasuda H, et al: Minocycline as adjunctive therapy for 
schizophrenia: an open-label study. Clin Neuropharmacol. 2008; 31(5):287-292.  
14. Khodaie-Ardakani MR, Mirshafiee O, Farokhnia M, et al: Minocycline add-on to 
risperidone for treatment of negative symptoms in patients with stable 
schizophrenia: randomized double-blind placebo-controlled study. Psychiatry 
Res. 2014; 215(3):540-546.  
15. Kelly DL, Sullivan KM, McEvoy JP, et al: Adjunctive minocycline in clozapine-
treated schizophrenia patients with persistent symptoms. J Clin 
Psychopharmacol. 2015; 35(4):374-381. 
16. Chaudhry IB, Hallak J, Husain N, et al. Minocycline benefits negative symptoms 
in early schizophrenia: a randomised double-blind placebo-controlled clinical trial 
in patients on standard treatment. J Psychopharmacol. 2012; 26:1185–1193. 
17. Liu F, Guo X, Wu R, et al. Minocycline supplementation for treatment of negative 
symptoms in early-phase schizophrenia: a double blind, randomized, controlled 
trial. Schizophr Res. 2014; 153:169-176.  
18. Miyaoka T, Wake R, Furuya M, et al: Minocycline as adjunctive therapy for 
patients with unipolar psychotic depression: an open-label study. Prog 
Neuropsychopharmacol Biol Psychiatry. 2012; 37(2):222-226.  
19. Soczynska JK, Mansur RB, Brietzke E, et al: Novel therapeutic targets in 
depression: minocycline as a candidate treatment. Behav Brain Res. 2012; 
235:302-317.  
20. Beristianos MH, Yaffe K, Cohen B, et al: PTSD and risk of incident 
cardiovascular disease in aging veterans. Am J Geriatr Psychiatry 2016; 
24(3):192-200. 
21. Levkovitz Y, Fenchel D, Kaplan Z, Zohar J, Cohen H. Early post-stressor 
intervention with minocycline, a second-generation tetracycline, attenuates post-
traumatic stress response in an animal model of PTSD. Eur 
Neuropsychopharmacol. 2015; 25(1):124-132. 
22. Bach DR, Tzovara, Vunder. Blocking human fear memory with the matrix 
metalloproteinase inhibitor doxycycline. Mol Psychiatry. 2017. doi: 
10.1038/mp.2017.65. 
 
 


11 
 
Table 1.  Study Visit Schedule 
Trial Phase 
Screening 
Baseline 
 
Follow-up Visits 
End 
of 
Study 
or ET 
Safety 
Follow-
up** 
Visit # 
V1 
V2 
V3* 
V4 
V5 
V6 
V7 
V8 
End of Week # 
-1 
0 
1 
2 
4 
8 
12 
13 
Informed Consent 
x 
 
 
 
 
 
 
 
Eligibility Criteria 
x 
 
 
 
 
 
 
 
Clinical Evaluation 
 
 
 
 
 
 
 
 
PCL-5 
x 
 
 
 
 
 
 
 
MINI 
x 
 
 
 
 
 
 
 
CAPS 
 
x 
 
 
 
 
x 
 
BDI-II 
x 
 
 
 
 
 
x 
 
CGI 
 
x 
 
x 
x 
x 
x 
x 
TMT  
 
x 
 
 
 
 
x 
 
COWA 
 
x 
 
 
 
 
x 
 
Medical Evaluation 
 
 
 
 
 
 
 
 
Medical History 
x 
 
 
 
 
 
 
 
Physical Exam 
x 
 
 
 
 
 
x 
 
Vital Signs 
x 
x 
 
x 
x 
x 
x 
x 
Lab Procedures 
 
 
 
 
 
 
 
 
Blood Draw 
x 
 
 
 
 
 
x 
 
Complete Blood Count (CBC) 
x 
 
 
 
 
 
 
 
Comprehensive Metabolic Panel (CMP) 
x 
 
 
 
 
 
 
 
Urinalysis 
x 
 
 
 
 
 
 
 
Urine Pregnancy Test 
x 
 
 
 
 
 
 
 
C-reactive protein (CRP) 
x 
 
 
 
 
 
x 
 
Interleukin 6 (IL-6) 
x 
 
 
 
 
 
x 
 
Tumor necrosis factor alpha (TNFα) 
x 
 
 
 
 
 
x 
 
Safety 
 
 
 
 
 
 
 
 
AE Records 
 
 
x 
x 
x 
x 
x 
x 
Other 
 
 
 
 
 
 
 
 
Drug Dispense/Account/Adjust 
 
x 
 
x 
x 
x 
x 
 
Con Meds 
x 
x 
 
x 
x 
x 
x 
x 
Patient Stipend 
x 
x 
 
x 
x 
x 
x 
x 
* Telephone visit, ** The safety follow-up visit will be conducted only for patients with 
ongoing adverse events.