Cognitive Processing Therapy Versus Sertraline for the Treatment of Post-traumatic Stress Disorder & Substance Use Disorder Egyptian Patients
Phase: PHASE1
Conditions: Psychologic Manipulation
Sponsor: British University In Egypt

Date:     01-01-2016                                                                                                                                         IRB Protocol CL-006 
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Study Number & Rev.: IRB Protocol CL-006 
Identifiers: 
NCT03469128 
Study Title: Cognitive Processing Therapy Versus Sertraline for the Treatment of Comorbid 
Substance Use Disorder and Post-Traumatic Stress Disorder in Egyptian patients   
Study Design: Randomized clinical trial 
Sponsor Name: The British University in Egypt 
Sponsor Address: El-Sherouk City, Cairo, Egypt 
Data Analysis: 01-01-2020 
Expected Completion Date: December 2020 
Principal Investigator: 
Dr. Amani Elbarazi, Clinical Practice Department, Faculty of 
Pharmacy, The British University in Egypt, P.O. Box 43, El-Sherouk 
City, Cairo 11837, Egypt 
 
STATEMENT OF CONFIDENTIALITY 
The information contained herein is confidential information that is the sole and exclusive 
property of The British University in Egypt and may not be divulged to any person (except as 
required by law) without the prior written consent of The British University in Egypt. 
 
 
Protocol signature page 
The undersigned has read and understood the trial protocol detailed above and agrees to 
conduct the trial in compliance with the protocol.   
 
Dr. Amani Elbarazi 
 
Amani 
 
BUE3570 
 
01-01-2016 
Principal Investigator 
(Please print name)  
 
Signature 
 
Site name or ID 
number  
 
Date 
 
Faculty of Pharmacy 
     كل
ــــــــــــ
ية الص
ـــــ
يدل ـــــــــ
ة 

Date:     01-01-2016                                                                                                                                         IRB Protocol CL-006 
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Study Title:  Cognitive Processing Therapy Versus Sertraline for the Treatment of Comorbid 
Substance Use Disorder and Post-Traumatic Stress Disorder in Egyptian patients   
 
Internal Reference Number / Short title: CPT for patients with PTSD and SUD  
Ethics Ref: 2016-2017PTBUE 
IRAS Project ID: IRB Protocol CL-006 
Date and Version No: 01-01-2016 
 
Principal Investigator: 
Dr. Amani Elbarazi, Clinical Practice Department, Faculty of 
Pharmacy, The British University in Egypt, P.O. Box 43, El-Sherouk 
City, Cairo 11837, Egypt 
Investigators:  
Osama A. Badary (Clinical Pharmacy Practice Department, Faculty 
of Pharmacy, Ain Shams University), Mohamed M. Elmazar 
(Pharmacology and Biochemistry Department, Faculty of 
Pharmacy, The British University in Egypt), Hanan Elrassas 
(Okasha Institute of Psychiatry, Department of Neuropsychiatry, 
Faculty of Medicine, Ain Shams University) 
Sponsor:  
The British University in Egypt, P.O. Box 43, El-Sherouk City, Cairo 
11837, Egypt. 
Funder: 
N/A 
Chief Investigator 
Signature:  
Dr. Amani Elbarazi 
Amani Elbarazi 
 
Statistician Signature:  
Prof. Mohamed M. Elmazar 
Declaration there is no potential conflicts of interest. 
 
 
 
 
 
 
 
 

Date:     01-01-2016                                                                                                                                         IRB Protocol CL-006 
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Trial Title:  Cognitive Processing Therapy Versus Sertraline for the Treatment of Comorbid 
Substance Use Disorder and Post-Traumatic Stress Disorder in Egyptian patients   
Protocol Date and Version No: 01-01-2016 
 
Protocol signature page 
The undersigned has read and understood the trial protocol detailed above and agrees to 
conduct the trial in compliance with the protocol.   
 
Dr. Amani Elbarazi 
 
Amani 
 
BUE3570 
 
01-01-2016 
Principal Investigator 
(Please print name)  
 
Signature 
 
Site name or ID 
number  
 
Date 
 
 
 
 
 
 

Date:     01-01-2016                                                                                                                                         IRB Protocol CL-006 
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TABLE OF CONTENTS 
1. 
KEY CONTACTS ................................................................................................................................... 6 
LAY SUMMARY .............................................................................................................................................. 7 
2. 
SYNOPSIS ........................................................................................................................................... 7 
3. 
ABBREVIATIONS ................................................................................... Error! Bookmark not defined. 
4. 
BACKGROUND AND RATIONALE ........................................................................................................ 8 
5. 
OBJECTIVES AND OUTCOME MEASURES ........................................................................................... 8 
6. 
STUDY DESIGN ................................................................................................................................. 11 
6.1. 
Study Participants .................................................................................................................... 11 
Comorbid PTSD & SUD patients .............................................................................................................. 11 
6.2. 
Inclusion Criteria ...................................................................................................................... 11 
7. 
PROTOCOL PROCEDURES ................................................................................................................ 12 
7.1. 
Recruitment ............................................................................................................................. 13 
7.2. 
Screening and Eligibility Assessment ....................................................................................... 13 
7.3. 
Informed Consent .................................................................................................................... 13 
7.4. 
Randomisation ......................................................................................................................... 14 
7.5. 
Blinding and code-breaking ..................................................................................................... 14 
7.6. 
Description of study intervention(s), comparators and study procedures (clinical) ............... 14 
7.6.1. 
Description of study intervention(s) .................................................................................... 14 
7.6.2. 
Description of comparator(s) .............................................................................................. 14 
7.6.3. 
Description of study procedure(s) ....................................................................................... 15 
7.7. 
Baseline Assessments .............................................................................................................. 15 
7.8. 
Subsequent Visits .................................................................................................................... 17 
7.9. 
Sample Handling ...................................................................................................................... 17 
7.10. 
Early Discontinuation/Withdrawal of Participants .................................................................. 17 
7.11. 
Definition of End of Study ....................................................................................................... 18 
8. 
SAFETY REPORTING ......................................................................................................................... 18 
8.1. 
Definition of Serious Adverse Events ...................................................................................... 18 
8.2. 
Reporting Procedures for Serious Adverse Events .................................................................. 18 
9. 
STATISTICS AND ANALYSIS ............................................................................................................... 18 
9.1. 
Statistical Analysis Plan (SAP) .................................................................................................. 18 
9.2. 
Sample Size Determination ..................................................................................................... 18 
9.3. 
The Level of Statistical Significance ......................................................................................... 19 
9.4. 
Procedure for Accounting for Missing, Unused, and Spurious Data. ...................................... 20 

Date:     01-01-2016                                                                                                                                         IRB Protocol CL-006 
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9.5. 
Procedures for Reporting any Deviation(s) from the Original Statistical Plan ........................ 20 
9.6. 
Health Economics Analysis ...................................................................................................... 20 
10. 
DATA MANAGEMENT ...................................................................................................................... 20 
10.1. 
Access to Data ......................................................................................................................... 20 
10.2. 
Data Recording and Record Keeping ....................................................................................... 20 
11. 
QUALITY ASSURANCE PROCEDURES ............................................................................................... 20 
11.1. 
Risk assessment ....................................................................................................................... 20 
11.2. 
Study monitoring ..................................................................................................................... 20 
12. 
PROTOCOL DEVIATIONS .................................................................................................................. 21 
13. 
SERIOUS BREACHES ......................................................................................................................... 21 
14. 
ETHICAL AND REGULATORY CONSIDERATIONS ............................................................................... 21 
14.1. 
Declaration of Helsinki............................................................................................................. 21 
14.2. 
Guidelines for Good Clinical Practice ...................................................................................... 21 
14.3. 
Approvals ................................................................................................................................. 21 
14.4. 
Reporting ................................................................................................................................. 21 
14.5. 
Participant Confidentiality ....................................................................................................... 22 
14.6. 
Expenses and Benefits ............................................................................................................. 22 
15. 
FINANCE AND INSURANCE .............................................................................................................. 22 
15.1. 
Funding .................................................................................................................................... 22 
15.2. 
Insurance ................................................................................................................................. 22 
16. 
PUBLICATION POLICY ....................................................................................................................... 22 
17. 
DEVELOPMENT OF A NEW PRODUCT/ PROCESS OR THE GENERATION OF INTELLECTUAL 
PROPERTY .................................................................................................................................................... 22 
18. 
ARCHIVING....................................................................................................................................... 22 
19. 
REFERENCES .................................................................................................................................... 22 
 
 
 

Date:     01-01-2016                                                                                                                                         IRB Protocol CL-006 
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1. KEY CONTACTS 
Chief Investigator 
Dr. Amani Elbarazi, Clinical Practice Department, Faculty of 
Pharmacy, The British University in Egypt, P.O. Box 43, El-Sherouk 
City, Cairo 11837, Egypt. 
Email: amani.safwat@bue.edu.eg 
Mobile: +(20)1020282555   
Sponsor 
The British University in Egypt, El-Sherouk City, Suez Road, Postal 
No. 11837, P.O. 43 
 Tel: 19283 (Hot Line), +20226890000- Fax: +20226300010/20 
www.bue.edu.eg 
Funder(s) 
N/A 
Clinical Trials Unit 
The Centre for Drug Research and Development (CDRD), Faculty 
of Pharmacy, The British University in Egypt, P.O. Box 43, El-
Sherouk City, Cairo 11837, Egypt. 
Tel.: 26890000 – 26300005/6/7/8 Ext.: 1820 
Statistician 
Dr. Amani Safwat Clinical Practice Department, Faculty of 
Pharmacy. The British University in Egypt, P.O. Box 43, El-Sherouk 
City, Cairo 11837, Egypt. 
Email: amani.safwat@bue.edu.eg 
Prof. Mohamed M. Elmazar (Pharmacology and Biochemistry 
Department, Faculty of Pharmacy, The British University in Egypt, 
P.O. Box 43, El-Sherouk City, Cairo 11837, Egypt. 
Email: mohey.elmazar@bue.edu.eg 
Committees 
Research Ethics Committee 
British University in Egypt Institutional Review Board  
Prof. Marwa Safar 
Pro. Basem Ngib 
Prof. Mostafa Kamal 
Tel.: 26890000 – 26300005/6/7/8 Ext.: 1840 

Date:     01-01-2016                                                                                                                                         IRB Protocol CL-006 
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LAY SUMMARY  
Background: Substance Use Disorder (SUD) often comorbid with Post-Traumatic Stress Disorder 
(PTSD). Aims: the primary objective of the present study was to investigate the effectiveness of 
Cognitive Processing Therapy (CPT) in comparison to Sertraline, and placebo in treating patients 
with comorbid Substance Use Disorder (SUD) and Posttraumatic Stress Disorder (PTSD) using a 
randomized controlled trial. The secondary objective was to determine the prevalence of PTSD 
among SUD patients. Methods: Data will be obtained through interviewing patients diagnosed 
with SUD. Patients will be interviewed by a clinician and asked to complete Mini-International 
Neuropsychiatric Interview (MINI), Clinician-Administered PTSD Scale (CAPS), Posttraumatic 
Stress Disorder Checklist (PCL-5), Beck Depression Inventory (BDI-II), Timeline Follow Back 
Interview (TLFB), and Brief Addiction Monitor (BAM). Patients with comorbid SUD and PTSD who 
will be randomized to one of the following groups: CPT, Sertraline, or Placebo. Assessments will 
be conducted at baseline, 3-, 6- and 12-months posttreatment. The primary outcomes will be the 
scores of CAPS, TLFB and BAM, while the secondary outcomes will be the scores of PCL, and BDI-
II. Results: we predict that CPT will result in greater reductions in CAPS scores in CPT, as compared 
to Sertraline and control groups.  
2. SYNOPSIS 
Study Title 
Cognitive Processing Therapy Versus Sertraline for the Treatment of 
Comorbid Substance Use Disorder and Post-Traumatic Stress Disorder 
in Egyptian patients. 
Internal ref. no. / short 
title 
CPT for patients with PTSD and SUD 
Study registration 
Study was registered at clinicaltrial.gov with Identifiers:
 
NCT03469128 on 03/12/2018 and Initial Release:
 
01/31/2018 
Sponsor  
The British University in Egypt, El-Sherouk City, Suez Road, Postal No. 
11837, P.O. 43 
 Tel: 19283 (Hot Line), +20226890000- Fax: +20226300010/20 
www.bue.edu.eg 
Funder  
N/A   
Study Design 
Randomized Clinical Trial 
Study Participants 
500 
Sample Size 
150 participants, all of them were patients with SUD and PTSD 
50 in the Cognitive Processing Therapy (CPT) group 
50 in the Sertraline group 
50 in the Placebo control group 
Planned Study Period 
the total length of the project: 2-3 years 
the duration of an individual participant’s involvement: 3 months  
Planned Recruitment 
period 
6-12 months of recruiting 

Date:     01-01-2016                                                                                                                                         IRB Protocol CL-006 
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Objectives 
Outcome Measures 
Timepoint(s) 
Primary 
 
To examine the 
efficacy 
of 
cognitive 
processing 
therapy (CPT) in 
treating comorbid 
SUD 
and 
PTSD 
compared 
to 
Sertraline 
and 
controls using a 
randomized 
controlled trial.  
Interview by clinician  
Complete:  Mini International 
Neuropsychiatric Interview 
(M.I.N.I), The Brief Addiction 
Monitor (BAM), PTSD 
Checklist–Civilian (PCL-5), 
Clinician-Administered PTSD 
Scale (CAPS). 
Assessments will 
be conducted at 
baseline, 3-, 6- 
and 12-months 
posttreatment. 
Secondary 
 
To investigate the 
prevalence of 
PTSD among 
patients with SUD 
Interview by clinician  
Complete:  Mini International 
Neuropsychiatric Interview 
(M.I.N.I), The Brief Addiction 
Monitor (BAM), PTSD 
Checklist–Civilian (PCL-5), 
Clinician-Administered PTSD 
Scale (CAPS). 
Patients 
diagnosed with 
SUD will be 
scanned for PTSD 
Intervention(s) 
Cognitive Processing Therapy (CPT) 
Comparator 
Sertraline 
Comparator 
Placebo control 
 
3. BACKGROUND AND RATIONALE 
Substance-use disorders (SUD) are patterns of symptoms resulting from the use of a 
substance that a person continues using, despite experiencing problems because of that 
substance (American Psychiatric Association, 2013).  Substance use disorder is a disease that 
affects a person's brain and behavior that caused by different factors including genetics 
(Goldman, Oroszi & Ducci, 2005), environmental (e.g., family's beliefs and attitudes) 
emotional, cognitive, social causes (peers who encourage drug use) and/or exposure to 
trauma (Hawkins, Catalano & Miller, 1992, Mayberry, Espelage & Koenig, 2009). Exposure to 
trauma and stress throughout a lifetime may result in increasing the probability of extensive 
alcohol consumption or using drugs as a maladaptive coping technique (Chilcoat & Breslau, 
1998, McLellan, 2017). Substance Use Disorder (SUD) often comorbid with Post-Traumatic 
Stress Disorder (PTSD) (Grant et al., 2015, Gulliver & Steffen, 2010, Seal et al., 2011). 
Posttraumatic Stress Disorder (PTSD) is characterized by intrusive, avoidance, hyperarousal, 
symptoms, and negative alterations in cognitions and mood (American Psychiatric 
Association, 2013). Psychological consequences of trauma could be in the form of the body's 
aches and pains, emotional suffering, destructive thoughts, and/or destructive behaviors 

Date:     01-01-2016                                                                                                                                         IRB Protocol CL-006 
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(Fernandez et al., 1999, Fernandez & Kerns, 2012).  Suffering caused by trauma may negatively 
impact a person's quality of life which can be manifested as a deterioration in his/her 
activities, feeling guilty, ashamed, and unworthy, and having destructive thoughts and 
behaviors about self, others, and the world (Kilpatrick, et al., 2013).  
Avoidance and escaping are very common maladaptive strategies among PTSD patients. One 
example of escaping maladaptive strategies of PTSD patients is using alcohol and/or drugs to 
avoid thinking of trauma/s they experienced. Therefore, several studies have shown high rates 
of (PTSD) among patients with (SUD) (Flanagan et al., 2016, Debell et al., 2014, Breslau, Davis, 
& Schultz, 2003). Unfortunately, patients with comorbid SUD and PTSD have worse results on 
medication, are less compliant with treatment, are more likely to drop out of therapy, have 
higher rates of self-destructive behaviors, and are less likely to seek pharmacotherapy and 
psychological help and support (Smith & Randall, 2012, Brady et al., 1994). These findings 
highlight the demanding need for the development of treatments that address both disorders. 
Meta-analysis research showed that medicine is considered one of the options to treat 
comorbid PTSD and SUD patients (Lee et al., 2016). Sertraline and paroxetine are the drugs 
that were approved by the Food and Drug Administration to treat PTSD symptoms (PTSD: 
National Center for PTSD) (Brady et al., 2005). Sertraline is considered a front-line medication 
for PTSD shown to also impact SUD outcomes (Huang et al., 2020). Sertraline would be 
expected to treat SUD based on prior literature (Petrakis & Simpson, 2017). A study conducted 
by Hien et al. (2015) compared psychotherapy treatment called Seeking Safety (SS) combined 
with either medication (Sertraline), or placebo in a sample of patients with comorbid PTSD 
and alcohol use disorder (AUD). Seeking Safety is a non-exposure-based psychosocial 
treatment that addresses both PTSD and substance/Alcohol use disorder (Najavits et al., 
1998). The results of Hien et al. (2015) showed that patients who received SS combined with 
sertraline had a significantly greater reduction in PTSD symptoms severity at the end of 
treatment than those who received SS combined with placebo. 
Studies suggest that treatments that address PTSD and SUD simultaneously can be cost-
effective, and have more effective therapeutic consequences (Mills et al., 2012).  The study of 
Foa, Hembree, & Rothbaum, 2007) suggested the Prolonged Exposure (COPE) with cognitive 
behavioral therapy as an effective treatment for PTSD and SUD. Cognitive Behavioral Therapy 
(CBT) helps PTSD & SUD patients to learn how to detect their maladaptive and destructive 
thoughts and debate them with logic and delete them (Sannibale et al., 2013). CBT also helps 
patients to gain useful behavioral skills, increase pleasant activities, and develop effective 
healthy relationships with other people (Lydecker et al., 2010, Roberts et al., 2015).  Also, 
Stress Inoculation Training (SIT) can help patients with PTSD to relax and be more attentive. 
SIT involves teaching patients coping skills to manage stress and anxiety caused by trauma 
(Meichenbaum, 2007). 
The International Society for Traumatic Stress Studies recommends Cognitive Processing 
Therapy (CPT) and Prolonged Exposure Therapy (PE) as effective treatments for patients with 
comorbid PTSD & SUD (Bisson et al., 2019). CPT is a well-described therapeutic protocol 
written by Resick and Schnicke (1993) and later updated by Resick (2001, 2008, 2014, 2017). 

Date:     01-01-2016                                                                                                                                         IRB Protocol CL-006 
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CPT is a 12-session evidence-based manualized treatment consists of trauma-focused therapy 
and cognitive therapy (Resick, Monson, Chard, 2014). CPT includes pretreatment assessment, 
educating patients about PTSD’s symptoms, types, causes, and how trauma can affect their 
daily life and functioning, identifying the “stuck points” which mean destructive thoughts 
related to the trauma, recognizing how trauma affects patient’s self-esteem, trust, power, 
safety and intimacy, personal growth and setting future life goals to have the valuable 
meaning of life (Resick, Monson, Chard, 2014).  
Randomized clinical trials reported that the (CPT) is successful in the management of PTSD 
with long-lasting 5 to 10-year outcomes and the highest impact and effect size of any PTSD 
therapy (e.g., Forbes, et al., 2012, Haagen, et al., 2015). Examining the impact of CPT among 
veterans who were diagnosed with PTSD and SUD and were participating in a six-week 
residential treatment program, showed that veterans with or without SUDs benefited from 
CPT equally (McDowell & Rodriguez, 2013). Kaysen et al., (2014) also investigated the 
effectiveness of CPT with patients with PTSD and AUD who attended at least 1 CPT session. 
Results have shown that CPT resulted in significant decreases in PTSD and depression over 
time. Further, Peck, et al., (2018) examined the effectiveness of 6-week day CPT-based 
treatment with patients diagnosed with PTSD and SUD. Their results showed that CPT 
significantly decreases maladaptive trauma-related cognitions. Bryan et al., (2018) examined 
the effectiveness of an intensive, 2-week CPT treatment program with veterans diagnosed 
with PTSD. They found that CPT significantly reduced PTSD symptom severity, rates of PTSD 
diagnosis, and suicide ideation. 
Studies suggested that effective treatment approaches of PTSD in Egypt include CBT (e.g., Jalal 
et al., 2017), trauma-focused therapy (e.g., Lambert & Alhassoon, 2015), and interpersonal 
psychotherapy (Meffert et al., 2014). Yet, our study is the first trial that compare CPT with 
Sertraline among an Egyptian population. 
However, despite the significant distress, impairment, and complicated clinical course facing 
patients with co-occurring SUD and PTSD, substantial gaps remain in the literature regarding 
effective treatment approaches. Recent encouraging advances include the psychosocial 
treatments and the examination of either psychosocial or pharmacological approaches to 
treating the complex presentation of SUD and PTSD. Therefore, the primary objective of the 
present study was to investigate the effectiveness of Cognitive Processing Therapy (CPT) in 
comparison to Sertraline in treating patients with comorbid SUD and PTSD. The secondary 
objective was to determine the prevalence of PTSD among SUD patients. We hypothesized 
that treating PTSD will echo in improvements in SUD. The current study marks the first 
randomized controlled trial to test the benefit of CPT for cooccurring (PTSD) and (SUD), with 
Sertraline, a front-line medication for PTSD shown to also impact (SUD) outcomes in the 
Arabic population. 
 
 
 

Date:     01-01-2016                                                                                                                                         IRB Protocol CL-006 
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4. OBJECTIVES AND OUTCOME MEASURES 
Objectives 
Outcome Measures  
Timepoint(s) 
of 
evaluation of this 
outcome 
measure 
(if 
applicable) 
Primary Objectives To examine 
the efficacy of cognitive 
processing therapy (CPT) in 
treating comorbid SUD and PTSD 
compared to Sertraline and 
controls using a randomized 
controlled trial.  
Mini-International 
Neuropsychiatric 
Interview 
(MINI), 
Clinician-
Administered PTSD Scale (CAPS), 
Posttraumatic 
Stress 
Disorder 
Checklist (PCL-5), Beck Depression 
Inventory (BDI-II), Timeline Follow 
Back Interview (TLFB), and Brief 
Addiction Monitor (BAM). 
Assessments 
were conducted 
at baseline, 3-, 6- 
and 
12-months 
posttreatment 
Secondary Objectives To 
investigate the prevalence of 
PTSD among patients with SUD 
Interview by clinician  
Complete: 
 
Mini 
International 
Neuropsychiatric Interview (M.I.N.I), 
Clinician-Administered 
PTSD 
Scale 
(CAPS). 
Patients 
diagnosed 
with 
SUD 
will 
be 
scanned for PTSD 
5. STUDY DESIGN 
This study is “Randomized clinical trial” 
We are going to interview SUD patients in this study. Participants are going to be asked to 
complete an eligibility and baseline assessments, including structured interviews and self-report 
measures to be classified as comorbid PTSD & SUD patients. If we found patients who are 
diagnosed with both PTSD & SUD, we are going to divide them into three groups: 1) CPT group, 
2) Sertraline group.  The third group will be placebo control group.  
All participants in all groups will complete standardized tests and checklists of PTSD and SUD 
symptoms as pre-treatment assessment, 3-, 6- and 12-months posttreatment 
 
5.1. Study Participants 
Comorbid PTSD & SUD patients  
5.2. Inclusion Criteria 
1) age older than 18 years, 2) patients meeting current diagnostic criteria for both PTSD and 
SUD as defined in DSM-5 3) have a good knowledge of English-language (reading, writing, 
and comprehension) because all assessments and therapy materials were in English 

Date:     01-01-2016                                                                                                                                         IRB Protocol CL-006 
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5.3. Exclusion Criteria 
having 1) mental retardation, 2) having schizophrenia (or any other psychotic disorders) 
and/or 3) being pregnant. 
6. PROTOCOL PROCEDURES  
The intervention will be either psychotherapy or Sertraline. The psychotherapy chosen to this 
study is the Cognitive Behavioural Therapy (CPT).  
Part I: each patient will attend 12 individual sessions with the therapist. The standard manual of 
CPT (Resick et al., 2014) is going to be employed but we will add some points related to substance 
use disorder treatment. We will add brief check-ins regarding any recent substance use or 
cravings at the beginning of sessions. We will teach patients to effectively process cognitions 
related to substance use by utilizing Challenging Belief Worksheets.  The outlines of the therapy 
during the sessions will be as follows. 
Sessions 1-4: education and Impact Statement  
- 
Explain to the patients the PTSD and SUD symptoms, causes, and types. Patients are going 
to be asked to write Impact Statement. Patients are going to be learned connections 
between events, thoughts, and feelings. Patients are going to write detailed accounts of 
the trauma including sensory details, thoughts, and feelings. CPT +A. 
Sessions 5-7 cognitive therapy: 
-Patients are going to be asked to write everything they recall about the traumatic event, 
their emotions, feelings, thoughts, sensory details related to traumatic event. Describe 
how the trauma affect their perceptions and emotions in different domains such safety, 
trust, power and control, esteem, and intimacy. The patients are going to be asked to read 
their writings about the trauma every day for a week. They are going to be taught to accept 
the emotions that come up while reading the trauma’s writings. 
- we will use Socratic questioning regarding stuck points. Stuck points are thoughts that 
keep repeating again and again like a record inside the patient’s brain. 
-learning about patterns of faulty thinking (problematic thinking patterns). For example, 
assimilation, which means when patients alter incoming information to match their 
previous beliefs. If a patient thinks bad things only happen to bad people, they will then 
believe that because they were assaulted, they were a bad person and deserved the 
trauma. Another example, I feel guilty because I have done something wrong otherwise 
why would I feel guilty. 
- we will employ challenging beliefs worksheets. 
Sessions 8-10 over accommodation 
-Modules and worksheets regarding: Safety, trust, power/control, esteem, intimacy. 
-patients are going to be asked to rewrite impact statements. 
- Patients are going to be asked to describe their emotions and thoughts about traumas 
but with more insight to identify the cognitive distortions and destructive thoughts by 
using worksheets. Patients are going to be taught to differentiate between facts, 
emotions, and thoughts. For example: “I am responsible for the trauma” “it is my fault to 
go there late”. patients are going to be taught the fact is: you were raped and assaulted, 
while your own thought is “my fault and mistake” your thoughts do not mean the fact or 
the reality at all. 
Sessions 11-12: develop a new thought or plan  

Date:     01-01-2016                                                                                                                                         IRB Protocol CL-006 
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Encourage the patients to set personal future goals to achieve personal growth by 
developing new supportive and positive, more optimistic thoughts. later patients are 
going to be learned to deal with the meaning of the stressful events and current beliefs 
about self and others.  
In both CPT individual and group sessions, we aimed to teach the patients to become their 
own therapists 
 
6.1. Recruitment 
Patients were recruited from Ain Shams University teaching Hospital, Cairo, Egypt. All patients' 
data and demographic information are stored at a much-secured place at the British University in 
Egypt (BUE). The present study is a Randomized Controlled Trial (RCT) with three groups: control 
group, Sertraline group and the CPT group.  
6.2. Screening and Eligibility Assessment 
The participants who will be eligible for the study will be approached and those who agreed to 
participate in the experiment protocol will be randomly assigned to either one of the three groups 
(CPT, Sertraline, Control).  
6.3. Informed Consent 
The patients signed the participants’ information sheet and consent form and were informed that 
the experiment will include two psychological assessments of SUD and PTSD. Patients who will be 
assigned to the experimental groups are going to be informed about the treatment protocol to 
investigate the efficacy of the treatment. All patients will sign the Informed Consent form before 
any study specific procedures are performed. Written and verbal versions of the patients 
Information and Informed Consent will be presented to the patients detailing the following 
points: the exact nature of the study; what it will involve for the participant; the implications and 
constraints of the protocol; the known side effects and any risks involved in taking part. It will be 
clearly stated that the participant is free to withdraw from the study at any time for any reason 
without prejudice to future care, without affecting their legal rights, and with no obligation to 
give the reason for withdrawal. 
The participant will be allowed as much time as wished to consider the information, and the 
opportunity to question the Investigator, their GP or other independent parties to decide whether 
they will participate in the study. Written Informed Consent will then be obtained by means of 
participant dated signature and dated signature of the person who presented and obtained the 
Informed Consent. The person who obtained the consent will be the Principal Investigator. A copy 
of the signed Informed Consent will be given to the participant. The original signed form will be 
retained at the study site. 
 

Date:     01-01-2016                                                                                                                                         IRB Protocol CL-006 
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6.4. Randomisation 
This is a three-group, repeated-measure, parallel-group, Randomized Control Trial design. 
Patients, study psychiatrists, and assessors will be blind to treatment condition assignment. 
Randomization blocks of three will be used to maintain equal group size. Participants will be re-
assessed at 3, 6, 12 months post-treatment. The pharmacy of Ain Shams Hospital will create 
sertraline and matching placebo kits with single-identifier numbers based on a random code that 
was provided to an unblinded statistician (Prof. Elmazar) who will instruct the psychiatrist how to 
distribute kits to patients. 
6.5. Blinding and codebreaking  
This is a three-group, repeated-measure, parallel-group, Randomized Control Trial design. 
Patients, study psychiatrists, and assessors were blind to treatment condition assignment. 
Randomization blocks of three were used to maintain equal group size. Outcome’s assessments 
were PTSD severity, substance use severity, and depression. The pharmacy of Ain Shams Hospital 
will create sertraline and matching placebo kits with single-identifier numbers based on a random 
code that will be provided to an unblinded statistician (Prof. Elmazar) who will instruct the 
psychiatrist how to distribute kits to patients. 
6.6. Description of study intervention(s), comparators and study procedures (clinical) 
If we could find comorbid PTSD & SUD patients in our study, then they will be divided into three 
groups: 1) CPT group  
2) the “medication group” who will receive Sertraline.  
3) The third group will be the placebo control group.  
All participants in all groups will complete standardized tests and checklists of PTSD and SUD 
symptoms as pre-treatment, post-treatment, 6-months, and 12-months assessments.  
 
6.6.1. Description of study intervention(s)  
6.6.2. Cognitive Behavioural Therapy (CPT) is a manual-guided therapy (Resick et al., 
2014) focused on PTSD symptom reduction. It is delivered in weekly 45–50-minute 
individual sessions during a 12-week timeframe. The outlines of the therapy during 
the sessions were as follows. Therapy is delivered in weekly 45–50-minute individual 
sessions during a 12-week timeframe. Sessions 1-4: education and Impact Statement, 
how the trauma affects their perceptions and emotions in different domains such as 
safety, trust, power and control, esteem, and intimacy. Sessions 5-7 cognitive 
therapy. Sessions 8-10 over accommodation. Patients asked to rewrite impact 
statements. Patients were asked to describe their emotions and thoughts about 
traumas but with more insight to identify the cognitive distortions and destructive 
thoughts by using worksheets. Sessions 11-12: develop a new thought or plan. 
Encourage the patients to set personal future goals (See Appendix D). 
6.6.3. Description of comparator(s)  

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Medication: To test drug adherence, the matching capsules will include sertraline or 
placebo as well as riboflavin. Compliance will be also checked by pill count. Participants 
receiving sertraline started on 50 mg daily and titrated up to 200 mg daily over 2 weeks. 
Participants will continue their full sertraline dose until the end of the trial (12 months). 
The “medication group” who will receive Sertraline. Prof. Hanan Elrassas is the psychiatrist 
at the Department of Neuropsychiatry, Faculty of Medicine, Ain Shams University, who is 
responsible for prescription of medicine for the patients. 
6.6.4. Description of study procedure(s) 
All participants in all groups will complete standardized tests and checklists of PTSD and SUD 
symptoms  
Assessments will include:  
During the time of the study, patients will meet weekly with a psychiatrist for the 
collection of a urine sample to examine drug use and any adverse events. After the study 
treatment phase, assessment interviews will be conducted by a blind independent 
assessor (Prof. Badary) at the end-of-treatment, 3, 6, 12 months posttreatment. 
 
Patient demographics: Personal Information and questions that will include closed-ended 
questions about participants' sociodemographic characteristics, personal, family-related, 
social, financial, educational, and academic-related problems.  
Mini-International Neuropsychiatric Interview (MINI) standard version 7.0.2 for DSM-5 is 
used for screening for SUD, and PTSD. The M.I.N.I. is the structured psychiatric interview 
of choice for psychiatric evaluation and outcome tracking in clinical trials with an 
administration time of approximately 15 minutes (Sheehan et al., 1998). 
Clinician-Administered PTSD Scale (CAPS-5; Weathers et al., 2015) is currently the gold-
standard assessment for PTSD and is used to assess PTSD's symptoms at pre-and post-
treatment. This 30-item structured interview was developed by staff at the U.S. 
Department of Veterans Affairs National Center for PTSD. The interview can generally be 
administered in 45-60 minutes. Each question in CAPS asks about both the frequency and 
the severity of each PTSD symptom. These questions are split into categories. Each 
criterion has several questions, and scores for each criterion are added up at the end. The 
CAPS-5 has demonstrated strong psychometric properties (Weathers, et al., 2018).  In the 
present study, CAPS-5 demonstrated strong interrater reliability (к=.90).  A random 
sample of 35 tapes was selected for evaluation of interrater reliability for the CAPS. 
Categorical diagnostic analyses revealed that the kappa coefficient for the overall PTSD 
diagnosis was 1.00 with 100% agreement. Kappa values and percentages of agreement 
for each of the three clusters of PTSD symptoms were as follows: reexperiencing (κ = .90; 
95% agreement), avoidance (κ = .85; 89% agreement), and arousal (κ = .80; 87% 

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agreement). Also, in the current sample, internal consistency (Cronbach’s alpha) across 
subscales was excellent at both time points (α = 0.94 and 0.96). 
Posttraumatic Stress Disorder Checklist (PCL-5) to measure the severity of the PTSD 
symptoms by the 20 items. The PCL-5 is a self-report measure that evaluates the degree 
to which an individual has been bothered in the past month by PTSD symptoms as 
described by DSM–5 (Weathers et al., 2013). Items are put on a 5-point Likert scale and 
are rated from 0 (not at all) to 4 (extreme), then items, are summed for a total severity 
score. Subscale severity scores are calculated by summing items in each of the four DSM–
5 PTSD symptom clusters: intrusions (Items 1–5), avoidance (Items 6 –7), negative 
alterations in cognitions and mood (NACM; Items 8 –14), and alterations in arousal and 
reactivity (AR; Items 15–20). PTSD was defined as endorsing a severity of at least a 2 
(moderate) for enough symptoms in each cluster to meet DSM–5 criteria. Evidence for 
the PCL for DSM-5 suggests that a 5-10-point change represents reliable change, and a 
10-20-point change represents clinically significant change (Weathers, et al. 2013).  The 
PCL has demonstrated acceptable psychometric properties (Sveen et al., 2016). For the 
present study, internal consistency was acceptable at both time points (α = 0.81 and 0.94) 
and Categorical diagnostic analyses revealed that the kappa coefficient for the overall 
PTSD diagnosis was .98 with 95% agreement. 
Beck Depression Inventory (BDI-II): was used to evaluate the severity of depressive 
symptoms. BDI-II is a 21-item, self-report rating inventory that measures characteristic 
attitudes and symptoms of depression (Beck, et al., 1996). The BDI takes approximately 
10 minutes to complete. Depression levels were defined as follows: minimal range = 0–
13, mild depression = 14–19, moderate depression = 20–28, and severe depression = 29–
63.  The BDI-II has demonstrated good reliability and validity (Beck et al., 1996). 
Cronbach’s alpha was excellent at pre-and post-treatment in the present study (α=0.90 
and 0.91, respectively) and one-week test-retest stability was high (.90). 
Timeline Follow Back Interview (TLFB; Sobell and Sobell, 1992), was administered to 
assess substance use patterns. Participants estimated their daily substance use in the 
previous 30 days with a detailed calendar to help them identify their uses and specific 
episodes of heavy use. TLFB has demonstrated good reliability as an instrument for the 
estimation of daily substance use (Sobell, Sobell, Leo, & Cancilla, 1988). 
Brief Addiction Monitor (BAM) to measure the SUD symptoms. The BAM is a 17-item 
self-report measure that assesses substance use. It includes the following subscales: 1) 
Use any alcohol or drug: if a patient scores a 1 or greater, it calls for further clinical 
attention 2) Risk Factors including cravings, physical health, sleep, mood, risky situations, 
or Family/social problems. If a patient scores a 12 or greater in the risk factors, he needs 
clinical attention 3) Protective factors include self-efficacy, self-help behaviors, 
religion/spirituality, work/school participation, adequate Income, sober support. If a 
patient scores a 12 or below in protective factors, it calls for clinical attention.  The 
previous studies showed acceptable characteristics of psychometric properties of BAM 
(e.g., Cacciola et al., 2013). In the current study, internal consistency (Cronbach’s alpha) 

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across subscales was excellent at both time points (α = 0.90 and 0.91) and Kappa values 
and percentages were obtained for SUD (κ = .95; 98% agreement). 
Urine drug screen (UDS) tests (CLIAwaived Inc.) will be administered weekly to assess for 
the presence of cocaine, marijuana, benzodiazepines, opioids, and amphetamines. Urine 
samples will be also tested for riboflavin to assess medication compliance.  
6.7. Baseline Assessments 
Interview by clinicians who had at least a Ph.D.’s degree in clinical psychology or Psychiatry. 
 Assessments including:  Mini-International Neuropsychiatric Interview (M.I.N.I), The Brief 
Addiction Monitor (BAM), PTSD Checklist–Civilian (PCL-5), Clinician-Administered PTSD Scale 
(CAPS). The primary outcome will be the total scores on the BAM, CAPS for DSM-5, the 
secondary outcome will be the total scores on the PCL, TLFB and BDI-II for DSM-5. Evaluations 
are going to be conducted at baseline and 6 months after the first assessment.  
Subsequent Visits 
participants will return to the hospital after 3, 6, and 12- months and the following assessments 
will be conducted: Interviews by clinicians - Clinician-Administered PTSD Scale (CAPS), Posttraumatic 
Stress Disorder Checklist (PCL-5), Beck Depression Inventory (BDI-II), Timeline Follow Back Interview 
(TLFB), and Brief Addiction Monitor (BAM) 
6.8. Sample Handling  
N/A 
6.9. Early Discontinuation/Withdrawal of Participants 
During the course of the study a participant may choose to withdraw early from the study 
treatment at any time. This may happen for several reasons, including but not limited to: 
• The occurrence of what the participant perceives as an intolerable AE.   
• Inability to comply with study procedures  
• Participant decision  
 
According to the design of the study, Participants can withdraw from the study but permit data 
and samples obtained up until the point of withdrawal to be retained for use in the study 
analysis.  No further data or samples would be collected after withdrawal.  
In addition, the Investigator may discontinue a participant from the study treatment at any time 
if the Investigator considers it necessary for any reason including, but not limited to: 
• Pregnancy 
• Ineligibility (either arising during the study or retrospectively having been overlooked at 
screening) 
• Significant protocol deviation 
• Significant non-compliance with treatment regimen or study requirements 
• Clinical decision  
 

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6.10. 
Definition of End of Study 
The study will be ended when we can get at least 50 patients with comorbid SUD and PTSD to 
be treated by the Cognitive processing therapy condition.  
7. SAFETY REPORTING  
Participation in this study involves answering questionnaires a risk of taking part could be related to any 
questions that they might consider too sensitive, intrusive, or upsetting. We will inform them “If you 
consider any of the questions as being inappropriate, please feel free not to give any answer”. Also, 
Patients in CPT group are going to be asked to write about their traumas they experienced. In these written 
accounts, participants will provide sensory details, thoughts, and feelings associated with the traumas. 
Unlimited time is allotted for the narrative and once it is completed patients are asked to read the account 
daily until the next session. In addition, between-session assignments are given after each treatment 
session. Cognitive processing therapy are going to be delivered individually weekly and group weekly 
sessions. 
7.1. Definition of Serious Adverse Events 
N/A 
7.2. Reporting Procedures for Serious Adverse Events 
N/A 
8. STATISTICS AND ANALYSIS 
SPSS will be used to analyse the data. The normality of the data distribution will be investigated 
using the Kolmogorov-Smirnov test. Homogeneity assumptions will be examined using, Levene’s 
tests. Mauchly’s test will be employed to examine the assumption of sphericity. 
8.1. Statistical Analysis Plan (SAP) 
Descriptive statistics (means, standard deviations, frequencies, percentages) were used 
to describe the sociodemographic and baseline characteristics of this sample. Bivariate 
analyses were employed to compare demographics and baseline symptom severity 
between the CPT, sertraline, and placebo group, and to explore the data for potential 
covariates for the main omnibus analyses. The main outcome variable for PTSD was CAPS 
& PCL total scores and was administered at pre-treatment (baseline) and all follow-up 
assessments. The main outcome variable for Depression was BDI-II total score and was 
administered at baseline and all follow-up assessments. The main outcome variables for 
SUD were, the total score on (BAM), the average number of substances used in the past 
30 days (PDU), and self-reported abstinence from the substance or/and alcohol in the 
prior 7 days, and negative urine tests at follow-up assessments. 
All analyses were conducted on the intent-to-treat sample. Generalized estimating 
equations (GEE) were utilized to model PTSD and SUD outcomes (Ballinger, 2004). A 

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temporal within-subjects autoregressive [AR (1)] correlation matrix was used to model 
participants across timepoints. Models were specified according to the distributions of 
the outcome measures. Identity link functions for normal distributions were used to 
model CAPS, PCL, BDI-II, and BAM severity scores, negative binomial models with log link 
were applied to the SUD measures of SU, PDU, and past 7 days abstinence rate was 
modelled using logit link for binary distribution. We use GEE, as it extends the generalized 
linear model, which processes corresponding data from repeat measurements, needs no 
assumption of parametric distribution and robust inference for an incorrect description 
of the internal correlation of subjects, and has good indications to the within-subject 
correlations (Zeger et al., 1988). Therefore, results are reported using parameter 
estimates for CAPS, PCL, BDI-II, RF, PF, incidence rate ratios for SU, PDU, and odds ratios 
for abstinence rate. All models included variables of time, treatment, time-by-treatment 
interaction, and any demographic or baseline diagnostic covariates for which there was 
a significant difference between groups. Consistent with prior studies applying similar 
analytic methods to comparable sample sizes (Schneier et al., 2012), and to reduce the 
probability of Type-II errors (Selvin, 1996), interactions that were at least trend-level (i.e., 
α < .10) were investigated for simple effects at end-of-treatment and follow-up time 
points. When an interaction did not meet this criterion, outcomes were modelled as main 
effects with covariates of time and baseline values of the outcome measures included in 
the model. All simple and main effects were considered significant at the α = .05 level 
(two-tailed). Bonferroni corrections were applied to all models of PTSD, depression, and 
SUD outcomes to control for Type I error. Sensitivity analyses with multiple imputations 
were conducted to further assess the influence of missing data in significant models. 
 
8.2. Sample Size Determination  
A priori statistical power analyses ensured that the sample size was sufficient to detect meaningful 
differences in primary outcomes. We set the following parameters based on previous research: the 
two-tailed test of significance, desired power=0.80, unstructured covariance matrix, four time-
points, correlation= 0.40 between repeated assessments, and attrition at 30% from pre-treatment to 
posttreatment. With a (50 per group), the study has 80% power to detect a medium effect size of 
0.55 for group (treatment types) difference on primary outcomes. 
Analysis populations 
All participants as randomised / registered / enrolled; all participants who will attend the 
intervention; all eligible participants  
8.3. The Level of Statistical Significance 
The level of significance to be used is < .05 
 
 

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8.4. Procedure for Accounting for Missing, Unused, and Spurious Data. 
Missing data are unavoidable in clinical research, potentially leading to bias and loss of 
precision. Multiple imputation (MI) will be utilized.  
8.5. Procedures for Reporting any Deviation(s) from the Original Statistical Plan 
All deviation(s) from the original statistical plan (if any) will be described in the final report.   
8.6. Health Economics Analysis  
N/A 
9. DATA MANAGEMENT 
All patients' data and demographic information are stored at a much-secured place at the 
British University in Egypt (BUE). All documents will be stored safely in confidential conditions. 
On all study-specific documents, other than the signed consent, the participant will be referred 
to by the study participant number, not by name. 
9.1. Access to Data 
Direct access will be granted to authorised representatives from the Sponsor and host hospital 
for monitoring and/or audit of the study to ensure compliance with regulations. 
9.2. Data Recording and Record Keeping 
All trial data will be entered on CRFs  
The participants will be identified by a unique trial specific number in any database.  The name 
and any other identifying detail will NOT be included in any trial data electronic file. 
The data will be retained for 7 years 
10. QUALITY ASSURANCE PROCEDURES 
The study will be monitored, in accordance with the current protocol, relevant regulations and 
standard operating procedures.  
10.1. 
Risk assessment  
A risk assessment and monitoring plan will be prepared before the study opens and will be 
reviewed as necessary over the course of the study to reflect significant changes to the protocol 
or outcomes of monitoring activities.  
10.2. 
Study monitoring  
The British University in Egypt (BUE) is the sponsor for the study. Regular monitoring will be 
performed according to the study specific Monitoring Plan. Data will be evaluated for 

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compliance with the protocol and accuracy in relation to source documents as these are defined 
in the study specific Monitoring Plan. Following written standard operating procedures, the 
monitors will verify that the clinical study is conducted, and data are generated, documented 
and reported in compliance with the protocol and the applicable regulatory requirements.  
11. PROTOCOL DEVIATIONS  
Any deviations from the protocol will be documented in a protocol deviation form and filed in 
the study master file. 
12. SERIOUS BREACHES 
If a serious breach is suspected the Sponsor must be contacted within 1 working day. The 
serious breach will be reviewed by the Sponsor and, if appropriate, the Sponsor will report it to 
the approving Ethical committee and the relevant host hospital within seven calendar days.  
13. ETHICAL AND REGULATORY CONSIDERATIONS 
13.1. 
Declaration of Helsinki 
The Investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki.  
13.2. 
Guidelines for Good Clinical Practice 
The Investigator will ensure that this study is conducted in accordance with relevant regulations 
and with Good Clinical Practice. 
13.3. 
Approvals 
Following Sponsor approval the protocol, informed consent form, participant information sheet 
will be submitted to an appropriate Research Ethics Committee (REC),  and host hospital for 
written approval. 
The Investigator will submit and, where necessary, obtain approval from the above parties for 
all substantial amendments to the original approved documents. 
13.4. 
Reporting 
The CI shall submit once a year throughout the study, or on request, an Annual Progress report 
to the REC Committee, HRA (where required) host organisation, Sponsor and funder (where 
required). In addition, an End of Study notification and final report will be submitted to the 
same parties. 
 

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13.5. 
Participant Confidentiality 
Issues of confidentiality were addressed by attributing a coding number to each participant’s data and by 
keeping all data in secured location (both physical and digital). All participants were made aware of these 
confidentiality procedures. 
13.6. 
Expenses and Benefits 
NA 
14. FINANCE AND INSURANCE 
14.1. 
Funding 
NA 
14.2. 
Insurance 
NA 
15. PUBLICATION POLICY 
The Investigators will be involved in reviewing drafts of the manuscripts, abstracts, press 
releases and any other publications arising from the study.  Authorship will be determined in 
accordance with the ICMJE guidelines and other contributors will be acknowledged. 
16. DEVELOPMENT OF A NEW PRODUCT/ PROCESS OR THE GENERATION OF INTELLECTUAL 
PROPERTY  
 
‘not applicable’ 
17. ARCHIVING 
Issues of confidentiality were addressed by attributing a coding number to each participant’s 
data and by keeping all data in secured location (both physical and digital). All participants 
were made aware of these confidentiality procedures. The data will be stored for 7 years. 
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