Conditions: Opioid Use Disorder, Severe, in Sustained Remission Opioid Use Disorder, Severe, in Early Remission Major Depressive Disorder
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 5
Healthy volunteers: no

Brief summary:
The purpose of the study is to examine whether an investigational medication called ketamine along with psychotherapy is an effective treatment for depression in participants with a history of opioid addiction who have not abused opioids in at least 3 months. Participants will receive ketamine through intramuscular injection along with psychotherapy weekly for 8 weeks. Participation for eligible subjects who decide to enroll (including post-medication follow-up visits) will last about 16 weeks or 4 months.

Detailed description:

Arms:
arm 1: Subjects will receive 8 weekly intramuscular injections of ketamine hydrochloride starting at 0.5 mg/kg and increasing to a maximum dose of 1.5 mg/kg or a total dose of 60 mg, whichever is lower. Ketamine administration will be accompanied by psychotherapy before, after and during the session.

Interventions: intervention 1: Ketamine-assisted psychotherapy
Intervention descriptions: intervention 1: Subjects will receive 8 weekly intramuscular injections of ketamine hydrochloride starting at 0.5 mg/kg and increasing to a maximum dose of 1.5 mg/kg or a total dose of 60 mg, whichever is lower. Ketamine administration will be accompanied by psychotherapy before, after and during the session.

Protocol document:
Prot_SAP_000.pdf: 
PROTOCOL TITLE: Ketamine-assisted psychotherapy for the treatment of persistent depression in 
abstinent opioid users 
 
NCT Number: Pro00115696 
 
Document date: August 18, 2022 
 
PRINCIPAL INVESTIGATOR:  
Eric T. Dobson, M.D. 
 
 
 
 
 


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TABLE OF CONTENTS 
1. OBJECTIVES/SPECIFIC AIMS ………………………………………………………………………. 4 
1.1. 
Introduction and Context 
1.2. 
Current Treatment 
1.3. 
Purpose and Objectives of the Study 
1.4. 
Specific Aims 
2. BACKGROUND ………………………………………………………………………………………… 6 
2.1. 
Role of Depression in Maintaining Abstinence From Opioids 
2.2. 
Glutamatergic Dysregulation Contributes to Both Depression and Addiction Pathology 
2.3. 
Clinical Trials for Depression Treatment 
2.4. 
Clinical Trials for Substance Use Disorder Treatment 
2.5. 
Novelty and Importance of the Current Study 
3. INTERVENTION TO BE STUDIED …………………………………………………………………... 7 
3.1. 
Overview of Study Medication 
3.2. 
Safety and Toxicity 
3.3. 
Study Drug, Dose, Mode of Administration and Justification 
4. STUDY ENDPOINTS …………………………………………………………………………………... 8 
4.1. 
Primary Outcomes 
4.2. 
Secondary Outcomes 
5. INCLUSION AND EXCLUSION CRITERIA/STUDY POPULATION ……………………………... 9 
5.1. 
Initial Screening Methodology 
5.2. 
Inclusion Criteria 
5.3. 
Exclusion Criteria 
5.4. 
Number of Subjects 
5.5. 
Setting 
5.6. 
Recruitment Methods 
6. CONSENT PROCESS ……………………………………………………………………………….   10 
6.1. 
Qualifications of Study Personnel Obtaining Informed Consent and Capacity of 
Participants 
6.2. 
Location of Informed Consent 
6.3. 
Method of Obtaining Consent 
6.4. 
Capacity of Participants to Give Informed Consent 
7. STUDY DESIGN/METHODS ………………………………………………………………………… 11 
7.1. 
Study Overview 
7.2. 
Duration of Treatment and Study 
7.3. 
Description of Assessments 
7.4. 
Schedule of Assessments 
7.5. 
Baseline Assessment Procedures 
7.6. 
Treatment Visit Procedures 
8. DATA MANAGEMENT ………………………………………………….…………………………… 13 
8.1. 
Data Analysis Plan 
8.2. 
Data Confidentiality Procedures 
8.3. 
Data Quality Control Procedures 
8.4. 
Study Documentation and Data Handling 
8.5. 
Privacy Protection and Confidentiality Assurances  
8.6. 
Data Sharing 


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9. PROVISIONS TO MONITOR THE DATA TO ENSURE THE SAFETY OF SUBJECTS …….. 15 
10. WITHDRAWAL OF SUBJECTS ……………….……………………………………………………. 15 
11. RISKS TO SUBJECTS…………………………. . .…………………………………………………. 16 
11.1. Overview 
11.2. Physical Risks 
11.3. Psychological Risks 
11.4. Abuse Liability  
11.5. Social Risks 
11.6. Legal Risks 
11.7. Economic Risks 
11.8. Unforeseeable Risks 
12. POTENTIAL BENEFITS TO SUBJECTS OR OTHERS ……………….………………………… 17 
16.1. Potential Benefits to Subjects 
16.2. Justification of Risks 
13. SHARING OF RESULTS WITH SUBJECTS ……………………….……………………………... 17 
14. DRUGS OR DEVICES ……………………………………..………….……………………………... 17 
14.1. Preparation, Handling and Storage of Study Medication 
14.2. Investigational New Drug (IND) Data 
15. REFERENCES ……………….……………………………………………………………………….. 17 
 
 


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1.0 OBJECTIVES/SPECIFIC AIMS 
1.1 Introduction and Context 
 
Depression is common in patients with opioid use disorder (OUD). In patients seeking buprenorphine-
naloxone treatment for OUD, about 1 in 4 have concurrent major depressive disorder (MDD) (Savant et 
al., 2013). Similarly, about one third to one half of patients enrolled in methadone maintenance treatment 
(MMT) are depressed (Peles, Schreiber, Naumovsky, & Adelson, 2007; Zhang et al., 2016). 
Unfortunately, depression occurs independent of MMT treatment duration suggesting that stabilization of 
OUD alone is not sufficient to improve mood symptoms (Peles et al., 2007). 
 
The relationship between OUD and depression is complex and bidirectional. Depressed patients who 
initiate opioid therapy are more likely to transition to long-term high-dose therapy and are at higher risk 
of opioid abuse or non-medical use (Sullivan, 2018). Conversely, chronic opioid use can cause 
neurobiological changes increasing negative affective states leading to higher suicide risk and continued 
opioid use (Rizk, Herzog, Dugad, & Stanley, 2021). Given this interdependence, concurrent treatment of 
both mood and opioid use disorder symptoms is paramount to prevent destabilization of either disorder 
(Vekaria et al., 2021).  
 
1.2 Current Treatment 
 
Current literature is limited regarding the treatment of depressed patients with OUD despite desire for 
positive mood being the most commonly cited reason for relapse in patients with OUD (Kadam, Sinha, 
Nimkar, Matcheswalla, & De Sousa, 2017; Unnithan, Gossop, & Strang, 1992).  A large, randomized 
placebo-controlled trial of imipramine in depressed patients receiving MMT showed promising results 
with 57% of imipramine-treated patients considered “responders” per clinical global impression compared 
with 7% of placebo-treated patients. Unfortunately, drop-out was common with only 84 of 137 patients 
completing an adequate 6 week trial (Nunes et al., 1998). Contrastingly, an RCT involving buprenorphine 
+ desipramine vs buprenorphine + placebo vs methadone + desipramine vs methadone + placebo failed 
to show efficacy of desipramine over placebo in 164 opioid- and cocaine-dependent patients. 
Concerningly, patients receiving buprenorphine + desipramine more frequently had urine drug screens 
positive for opioids than those receiving buprenorphine + placebo (Kosten, Falcioni, Oliveto, & Feingold, 
2004).  
 
Selective serotonin reuptake inhibitors (SSRIs), the first line treatment in patients with moderate-to-
severe MDD have a mixed-to-negative evidence base in co-occurring MDD and OUD (Carpenter, Brooks, 
Vosburg, & Nunes, 2004; Petrakis et al., 1998). Regarding the treatment of depression in patients on 
opioid agonist therapy, a 2010 Cochrane review found there is “low evidence supporting the clinical use 
of antidepressants to treat depression in opioid dependence”, while also noting that current literature is 
limited  (Pani, Vacca, Trogu, Amato, & Davoli, 2010). This finding was further supported by a subsequent 
meta-analysis examining antidepressant use in patients engaged with MMT (Pedrelli et al., 2011). Given 
the prevalence of depression in patient with OUD regardless of stage of recovery and ineffectiveness of 
current interventions, more effective treatments for depression in OUD are critically needed. 
1.3 Purpose and Objectives of the Study 
The primary objective of the proposed study is to preliminarily explore the feasibility, efficacy, and 
tolerability of ketamine-assisted psychotherapy in treatment of MDD in patient with OUD currently in early 
or sustained remission by DSM-V criteria. We seek to enroll 10 individuals with current moderate-to-
severe major depression despite ongoing abstinence from opioids.  
1.4 Specific Aims 
To achieve these objectives, the following Specific Aims are proposed: 


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Specific Aim 1: To preliminarily explore the efficacy of ketamine-assisted psychotherapy 
in reducing symptoms of depression using the Montgomery Asberg Depression Rating 
Scale (MADRS). 
Specific Aim 2: To preliminarily explore the tolerability of ketamine-assisted 
psychotherapy in treatment of depression including adverse effects, cravings and relapse 
 
 
 


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2.0 BACKGROUND 
 
2.1 Role of Depression in Maintaining Abstinence From Opioids 
Negative affect has been found to be a key mediator in failure to achieve abstinence and depression is 
a frequently seen comorbidity in OUD in all stages of treatment and recovery. Nearly two out of three 
persons entering treatment for opioid detoxification screen positive for depression (Brienza et al., 2000; 
Stein, Santiago Rivera, Anderson, & Bailey, 2017; Volkow, 2004). In patients seeking buprenorphine-
naloxone treatment for OUD, about 1 in 4 have concurrent major depressive disorder (MDD) (Savant et 
al., 2013). Similarly, about one third to one half of patients enrolled in methadone maintenance treatment 
(MMT) are depressed (Peles et al., 2007; Zhang et al., 2016). Unfortunately, depression occurs 
independent of MMT duration suggesting that stabilization of OUD alone is not sufficient to improve mood 
symptoms (Peles et al., 2007) and desire for improvement in mood is the most commonly cited reason 
for relapse in OUD following initial addictions treatment (Huhn et al., 2019; Kadam et al., 2017; Volkow, 
Jones, Einstein, & Wargo, 2019). In addition to contributing to relapse and being a risk for unintentional 
overdose, OUD is an independent risk factor for completed suicide. A national cohort study of veterans 
(n=4,863,086) found that after controlling for psychiatric and medical comorbidities, overall substance 
use was still associated with a 1.67 hazard ratio for suicide in men and 2.15 in women. Furthermore, in 
women, OUD was associated with the highest hazard ratio for suicide of any substance of abuse at 2.33 
(Bohnert, Ilgen, Louzon, McCarthy, & Katz, 2017). 
 
2.2 Glutamatergic Dysregulation Contributes to Both Depression and Addiction Pathology 
Glutamatergic dysregulation in the prefrontal cortex and mesolimbic regions (including the amygdala and 
the nucleus accumbens) has been implicated in addiction pathology across multiple substances of abuse 
(Gass & Olive, 2008). Similarly, depression has been shown to have aberrant glutamate signaling 
(Murrough, Abdallah, & Mathew, 2017; Niciu et al., 2014). On a cellular level, astrocytes are responsible 
for maintaining glutamate homeostasis (Parpura & Verkhratsky, 2012) and both depression and addiction 
have been linked to impaired ability of astrocytes to upregulate glutamate (Rajkowska & Stockmeier, 
2013; Scofield & Kalivas, 2014). Ketamine is a noncompetitive antagonist of NMDA glutamatergic 
receptors which has been widely used for pain control in conjunction with general anesthesia since it was 
FDA approved in 1970.  
 
2.3 Clinical Trials for Depression Treatment 
Results from several meta-analyses indicate that ketamine can induce ultra-rapid improvements in 
depression and suicidality (Han et al., 2016; Wilkinson et al., 2017). This remission is most enduring in 
individuals with a family history of substance use disorders (Niciu et al., 2014). It is widely accepted that 
all currently approved pharmacotherapy classes for depression (serotonin reuptake inhibitors, 
monoamine oxidase inhibitors, and tricyclic antidepressants) are associated with a delayed onset of anti-
depressant activity of 2-4 weeks. A meta-analysis of nine high-quality studies showed that ketamine was 
significantly more effective than placebo in reducing symptoms of major depressive disorder at 24 hours, 
72 hours, and 7 days post-infusion (Han et al., 2016). Additionally, results from a recent meta-analysis of 
ten clinical trials showed accumulating evidence that ketamine can significantly reduce suicidal ideation 
within 24 hours with moderate to large effect sizes (Wilkinson et al., 2017). The overall duration of anti-
depressant response was found to last between 3-12 days (Andrade, 2017). However, in a subgroup 
analysis, positive family history of alcoholism was found to be associated with a significantly longer 
duration of anti-depressant efficacy, averaging 17 days for the family history positive group and 3.6 days 
for the family history negative group (Niciu et al., 2014). This suggests that the genetics underlying 
substance use confer a stronger response to the effects of ketamine. 
 
2.4 Clinical Trials for Substance Use Disorder Treatment 
Ketamine has shown early evidence of efficacy in the treatment of substance use disorders. One study 
evaluating the adjunctive use of ketamine in heroin use disorder showed that a single-session of high-


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dose (2 mg/kg IM) ketamine demonstrated one-month abstinence rates of 85% compared to 55% 
abstinence in the low dose group (0.2 mg/kg IM), and one-year abstinence rates of 24% in the high dose 
group as compared to 6% in the low-dose control group (E. Krupitsky et al., 2002). In a follow-up study 
comparing three repeated sessions of ketamine infusions with concurrent psychotherapy to single-
session treatment, abstinence rates were increased to 50% in the 3 session group as compared to the 
single session rate of 22% (Evgeny M Krupitsky et al., 2007). Related studies found that ketamine is 
useful as an adjunct to psychotherapy in the treatment of alcohol use disorder (E M Krupitsky & Grinenko, 
1997) with one-year complete abstinence rates of 65.8% in the ketamine-assisted psychotherapy group 
compared to 24% in the control psychotherapy group. Intriguingly, the anti-depressant response to 
ketamine occurs primarily after the drug has been cleared from the body, suggesting that its primary 
effects are mediated through downstream processes. More recently, ketamine has been studied in 
cocaine use disorder and found to improve levels of motivation to quit using and to reduce cocaine craving 
(Elias Dakwar, Levin, Foltin, Nunes, & Hart, 2014) and reduce rates of cocaine self-administration by 
67% relative to baseline (E Dakwar, Hart, Levin, Nunes, & Foltin, 2017; E Dakwar et al., 2018). 
Additionally, a single dose of ketamine combined with motivational enhancement therapy has been 
shown to increase abstinence and increase time to relapse in subjects with alcohol use disorder (Elias 
Dakwar et al., 2020) while a single dose of ketamine combined with mindfulness-based relapse 
prevention has yielded similar results in subjects with cocaine dependence (Elias Dakwar et al., 2019). 
Finally, ketamine combined with motivational enhancement therapy and mindfulness-based relapse 
prevention has shown promising open-label evidence for the treatment of cannabis use disorder (Azhari 
et al., 2021). 
 
2.5 Novelty and Importance of the Current Study 
Past  studies have shown promising results for ketamine in the rapid treatment of MDD (Han et al., 2016) 
particularly in those with a family history of substance use (Niciu et al., 2014), however no prior studies 
have investigated the efficacy of ketamine-assisted psychotherapy in the treatment of depressed 
participants with OUD currently in early or sustained remission. 
  
 
3.0 
INTERVENTION TO BE STUDIED    
3.1 Overview of Study Medication 
Ketamine was originally FDA approved in 1970 for pain control in conjunction with general anesthesia 
(Ketalar, 2021).  The drug has since been evaluated in academic settings for the treatment of pain and a 
multitude of psychiatric indications.  Ketamine has been increasingly studied in academic settings and 
used off-label in private practice settings over the past 10 years (Wilkinson et al., 2017).  Ketamine 
undergoes extensive hepatic first pass metabolism, with an oral bioavailability of approximately 16% ( 
(Mathew et al., 2012). For induction of anesthesia, doses of 1 to 4.5 mg/kg IV or 6.5 to 13 mg/kg IM are 
recommended (Ketalar, 2021).   
 
3.2 Safety and Toxicity 
The acute toxicity of ketamine has been studied in multiple species.  In mature mice and rats, the 
intraperitoneal LD50 values have been shown to be approximately 100 times the average human 
intravenous dose (Ketalar, 2021).  Repeated, daily intravenous injections have been studied in rats, and 
dogs for as long as 6 weeks with excellent tolerability (Ketalar, 2021). Similarly, twice weekly treatments 
in monkeys over a four- to six-week period were well tolerated (Ketalar, 2021).  At sub-anesthestic doses 
in human clinical trials for depression, the most clinically significant physical adverse event from ketamine 
is a transient increase in blood pressure, which was experienced by 29.8% of participants with a mean 
systolic blood pressure increase of 19.6 mmHg (p<0.001) and a mean diastolic blood pressure increase 
of 13.4 mmHg (p<0.001, (Wan et al., 2015)).  Small, but statistically significant changes in perception 
(including derealization, depersonalization, distortion of time and space, and sense of illusion) were 
categorized as “feeling strange or unreal” and were experienced by 11.7% of participants. The average 


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peak score of 4.5 on the Brief Psychotic Rating Scale is consistent with very mild symptom severity (Wan 
et al., 2015). 
 
3.3 Study Drug, Dose, Mode of Administration and Justification 
Ketamine is concentrated at a dose of 100 mg/ ml and will be administered by intramuscular administration 
in the amount of 0.5 mg/kg with plan to flexibly titrate by 0.25 mg/kg each session based on tolerability to 
a maximum weight-based dose of 1.5 mg/kg. Total dose on a given day will be limited to 60 mg regardless 
of subject’s weight. While formal dose response studies for depression are lacking, ketamine has been 
most widely studied for psychiatric indications at 0.5 to 1.0 mg/kg given intravenously.  Recent studies 
have shown that intramuscular ketamine may be as effective as intravenous ketamine for depression and 
may be more practical clinically (Chilukuri et al., 2014; Xu et al., 2016). Although there are only a few 
studies evaluating the use of ketamine in the treatment of substance use disorders, doses in these trials 
have ranged from 0.5 to 0.8 mg/kg given intravenously or 2 mg/kg given intramuscularly (Jones, Mateus, 
Malcolm, Brady, & Back, 2018). When given intramuscularly, ketamine has a peak time of 5-30 minutes 
following injection and a bioavailability of 86-97% (Grant, Nimmo, & Clements, 1981). Of note, ketamine 
elimination clearance is high with a half-life of 2-3 hours and clearance in women that is up to 20% higher 
than men (Mion & Villevieille, 2013). 
 
4.0 STUDY ENDPOINTS  
 
4.1 Primary Outcome 
 
Montgomery Asberg Depression Rating Scale (MADRS; (Montgomery & Asberg, 1979)). The MADRS is 
a clinician administered, 10-item questionnaire of depression severity. The total score ranges from 0-60, 
with scores of 0-6 considered normal (non-depressed), 7-19 indicative of mild depression, 20-34 
indicative of moderate depression, and 35-60 indicative of severe depression.  Individuals scoring 20 or 
higher on the MADRS will be included in the study. The MADRS evaluates the following symptoms of 
depression: 1) clinical appearance of sadness, 2) self-reported sadness, 3) inner tension, 4) reduced 
sleep, 5) reduced appetite, 6) concentration difficulties, 7) lassitude, 8) inability to feel, 9) pessimistic 
thought process, and 10) thoughts of suicide. The MADRS has a sensitivity of 94% and a specificity of 
83%, has been shown to have high internal consistency, and correlates well with other measures of 
depression such as the Hamilton Depression Scale.     
 
4.3 Exploratory Outcomes 
Exploratory outcomes will include changes in characteristics related to opioid addiction including craving 
for opioids (Visual Analog Scale) and related areas of psychiatric functioning. 
 
• Beck Depression Inventory (BDI-II; Beck, Steer, & Brown, 1996). A widely used 21-item self-
report measure of depressive symptoms. 
• Visual Analog Craving Scale (VAS; McMillan & Gilmore-Thomas, 1996). At baseline, during 
the interventional visits, and at each follow-up visit, subjects will be asked to report on the 
frequency, duration, and intensity of their opioid cravings on a 10 point (100 mm) VAS. This 
approach has been shown to yield a reliable and valid measure of craving in previous 
research.  
• Timeline Follow-Back (TLFB; Linda C. Sobell, 1992): The TLFB obtains retrospective self-
report of substance use by using a calendar and memory prompts to stimulate recall. 
Quantity and frequency assessments are made using this instrument (e.g., total amount of 
opioids used, percent of days using) as well as abstinence (yes/no). TLFB yields 
consistently high test-retest correlations and correlates well with other self-reports and 
collateral reports. The TLFB will assess consumption of opioids for 60 days prior to study 


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entry, during the interventional phase and the follow-up phase. Use of nicotine and other 
drugs of abuse, including prescription drugs, will also be assessed using the TLFB.   
• Generalized Anxiety Disorder Screener (GAD-7; Spitzer, Kroenke, Williams, & Löwe, 
2006)). The GAD-7 is a 7-item self report instrument that will assess generalized anxiety 
symptomology.  
• Five Facets of Mindfulness Questionnaire (FFMQ; Baer, Smith, Hopkins, Krietemeyer, & 
Toney, 2006): The FFMQ assesses five components of mindfulness including observation, 
non-judgement of experience, non-reactivity to inner experience, acting with awareness, 
and description of experience.   
• PTSD Checklist (PCL-5; Blevins, Weathers, Davis, Witte, & Domino, 2015): The PCL-5 is a 
20-item self-report measure. The PCL-5 is similar in form to the PTSD Checklist (PCL) 
based on the DSM-5 (Weathers et al., 1993), which has excellent psychometric 
characteristics for screening and as a secondary indicator of PTSD symptom severity 
(McDonald & Calhoun, 2010). 
• Insomnia Severity Index (ISI; Morin, Belleville, Bélanger, & Ivers, 2011). The ISI is a 7-item, 
self-report measure that assesses perceived severity of insomnia.  The items sum to 
produce a total score (range 0–28).  The ISI has an internal consistency alpha coefficient of 
0.74, and has shown convergent validity with other measures such as the Pittsburgh Sleep 
Quality Index and sleep diaries). 
• Brief Pain Inventory (BPI; (Cleeland & Ryan, 1994). This 9-item questionnaire uses a 10-
point Likert scale to assess the severity of pain and its interference on difference aspects of 
quality of life and function.  
• Mystical Experience Questionnaire (MEQ). This 30-item self-report questionnaire was 
developed and validated through factor analysis of retrospective accounts of profound 
experience with psilocybin-containing mushrooms. It includes four factors: transcendence 
of time and space, ineffability, positive mood and mystical (internal unity, external unity, 
noetic quality, and sacredness)  (Barrett, Johnson, & Griffiths, 2015; Maclean, Leoutsakos, 
Johnson, & Griffiths, 2012). 
   
5.0 
INCLUSION AND EXCLUSION CRITERIA/STUDY POPULATION 
5.1 Initial Screening Methodology 
Initial screening eligibility will be conducted by the PI or trained research personnel.  Subjects with a self-
reported history of depression and opioid misuse or illicit opioid use for which they report being abstinent 
for at least 3 months (early remission) will be eligible to complete informed consent and baseline 
evaluation. 
 
5.2 Inclusion Criteria 
A subject may be eligible for enrollment if all the following inclusion criteria apply within the thirty days 
prior to first experimental session: 
1. 
Between the ages of 18 to 64 years old.  
2. 
Able to provide informed consent.  
3. 
Meet DSM-5 criteria for Major Depressive Disorder, without psychotic features based on 
clinical interview. 
4. 
Score at least 20 on the Montgomery-Asberg Depression Rating Scale (MADRS, moderate 
or severe depression).  
5. 
Must meet criteria for opioid use disorder in early or sustained remission (3 months or great) 
by DSM-5 based on clinical interview. 
6. 
Subjects taking other psychotropic medications (e.g. anti-depressants, anxiolytics, 
methadone, buprenorphine, naltrexone) must be maintained on a stable dose for at least four 
weeks before study initiation.  
 


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5.3 Exclusion Criteria 
Subjects will be excluded from the study if any of the following criteria apply: 
1. 
They are considered an immediate suicide risk by clinician assessment, self-report a suicide 
attempt within the past year or felt to be likely to require hospitalization during the study. 
2. 
Subjects who meet DSM-5 criteria for current bipolar disorder based on clinical interview. 
3. 
Subjects who meet DSM-5 criteria for current or history of psychotic spectrum disorders based 
on clinical interview.   
4. 
Subjects meeting DSM-5 criteria for current substance use disorder (i.e., not in early or 
sustained remission) other than tobacco use disorder. 
5. 
Subjects who report use of ketamine >20 times in the past or who meet DSM-5 criteria for 
Other Hallucinogen Use Disorder due to ketamine use including subjects who are currently in 
early or sustained remission. 
6. 
Women who are pregnant or nursing, and women who do not consent to use methods of 
highly effective birth control during the interventional phase of the study. 
7. 
Subjects with hypertension as defined by a baseline visit systolic blood pressure (SBP) >140 
mmHg or a diastolic blood pressure (DBP) >90 mmHg. 
8. 
A history of allergic or other adverse reaction to ketamine (or its excipients). 
9. 
Clinically significant physical exam findings or self-reported medical conditions for which a 
transient increase in blood pressure could be significantly detrimental (e.g. glaucoma, 
aneurysmal disease, cardiovascular disease, or end-stage renal disease). 
10. QTc will be measured in subjects currently taking methadone and those with QTc 450ms or 
longer will be excluded. 
11. Subjects who live greater than 20 miles from the study site and cannot arrange their own 
transportation will be excluded from the study.   
12. Subjects with clinically significant kidney or liver impairment.   
 
 
5.4 
NUMBER OF SUBJECTS 
Approximately 10 subjects are planned for enrollment in this study with no gender, race, or ethnicity 
exclusions.  
 
5.5 
SETTING 
All procedures will be conducted in private research study rooms on MUSC campus. 
 
5.6 
RECRUITMENT METHODS 
Recruitment will be conducted through online (i.e. Craigslist) and flyer advertisements throughout the 
hospital and outpatient clinics at MUSC and other local clinics providing OUD treatment.   
 
Initial screening eligibility will be conducted by the PI or trained research personnel.  Subjects with a self-
reported history of depression and opioid misuse or illicit opioid use for which they report being abstinent 
for at least 3 months (early remission) will be eligible to complete informed consent and baseline 
evaluation. 
 
6.0 
CONSENT PROCESS 
6.1 Qualifications of Study Personnel Obtaining Informed Consent and Capacity of Participants 
The research team have completed (or will complete upon hiring) the Miami Collaborative IRB Training 
Initiative (CITI) course and its associated tests in research ethics.  Only the PIs or Co-I’s will obtain 
informed consent.   
 
6.2 Location of Informed Consent 


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Informed consent will be obtained at the study research offices, in a private and interruption-free 
environment. 
 
6.3 Method of Obtaining Consent 
Study personnel will ensure that the participant is given full and adequate written and verbal information 
about the nature, purpose, possible risks and benefits of the study.  There will be no mandatory waiting 
period prior to obtaining informed consent, however participants will not be required to make a decision 
at the time of initial contact.  Participants will also be allowed to discuss the study with family or other 
individuals prior to giving their informed consent.  After participants have reviewed the informed consent 
document, participants will be asked to relay their understanding of key elements related to the study 
procedures (i.e. voluntary nature of participation, basic study visit procedures, duration of study, 
anticipated risks and benefits) to ensure their understanding of the study prior to obtaining informed 
consent.  Consent content will be reviewed as necessary to ensure that subjects have an adequate 
understanding to provide initial and ongoing consent.  The participant’s signed and dated informed 
consent will be obtained before conducting any study tests or procedures that are not related to their 
routine care.  The Investigator will maintain the original, signed informed consent document.  A copy of 
the signed informed consent document will be given to the participant. 
 
6.4 Capacity of Participants to Give Informed Consent 
No vulnerable populations (e.g. children, cognitively impaired individuals, incarcerated individuals, or 
pregnant women) will be included in the study, and informed consent must be obtained directly from the 
participants.   
 
7.0 STUDY DESIGN/METHODS 
7.1 Study Overview 
This is an open label trial of ketamine-assisted psychotherapy to assess the efficacy and safety of weekly 
intramuscular injections of ketamine along with multimodal psychotherapy, including supportive, non-
directive and insight-oriented components, for decreasing symptoms of MDD in subjects with OUD in early 
or sustained remission. Psychotherapy will include setting goals for treatment of subject’s depression as 
well as setting an intention or focus for each medication session. After medication administration, therapy 
will include supportive talk and guidance during acute medication effects. At the end of each session, the 
subject will be encouraged to reflect on his or her experience as it relates to their intention and broader 
goals. Finally, the subject will be encouraged to build insight into their depression and develop behavioral 
goals to enact their insights and reach their goals. 
 
Subjects will participate in a baseline visit to complete informed consent as well as complete assessments 
to evaluate study eligibility and collect baseline data. Eligible participants will return for the initial ketamine 
intervention procedure.  Participants will be subsequently monitored until they have returned to baseline 
based on clinical assessment during which time they will complete measures assessing their perception 
of the interventional experience 
 
7.2 Duration of Intervention and Study 
Participants will complete a total of 12 study visits (including baseline assessment and follow-up 
assessments) as shown in Figure 1.  Medication sessions with intramuscular ketamine will occur weekly 
for eight weeks. Participants will meet virtually or in person for follow-up 1, 2, 4, and 8 weeks following 
final medication session. 
 
7.3 Schedule of Assessments 
The instruments to be used are standardized, have good psychometric properties, and are widely used. 
The schedule of study assessments is provided in Table 1. 
 


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Table 1: Schedule of Assessments 
 
Instrument Name 
Purpose 
 
TIME 
POINT 
 
BL 
(Wk 0) 
Tx 1-8 
(Wk 1-8) 
Follow-up 
(Wk 9, 10, 12, 16) 
Self-Reports and Consents 
 
Informed Consent 
Obtain informed consent 
X 
 
 
Demographics Form 
Sample characterization 
X 
 
 
Beck Depression Inventory-II 
Self-reported assessment of 
depression symptom severity 
X 
X 
X 
Visual Analog Scale (VAS) 
Measure subjective levels of 
opioid craving 
X 
X 
X 
General Anxiety Disorder 
(GAD-7) 
Self-report of anxiety symptom 
severity 
X 
X 
X 
Mystical Experiences 
Questionnaire (MEQ) 
Measure of perceptual 
experiences 
 
X 
 
Brief Pain Inventory 
Measure of pain and quality of 
life 
X 
X 
X 
Insomnia Severity Index (ISI) 
Assess insomnia and sleep 
quality 
X 
X 
X 
Five Facets of Mindfulness 
(FFMQ) 
Assess aspects of mindfulness 
related 
X 
X 
X 
PTSD Checklist (PCL-5) 
Measure of PTSD symptoms 
X 
X 
X 
Fagerstrom Test of Nicotine 
Dependence (FTND) 
Measure of nicotine dependence 
X 
X 
X 
Timeline Follow-Back (TLFB) 
Measure of substance use 
X 
X 
X 
Clinician Assessments 
History and Physical Exam 
Eligibility assessment 
X 
 
 
Vital Signs Measurement 
Obtain readings of blood 
pressure, pulse, temperature, 
respirations and pulse oximetry 
X 
X* 
 
Montgomery-Asberg 
Depression Rating Scale 
(MADRS) 
Primary Outcome: Clinician 
assessed measure of depression 
symptom severity 
X 
X 
X 
Pre-screening Questionnaire 
To assess for basic eligibility 
criteria before completing a full 
baseline visit. 
X 
 
 
 
Laboratory and Procedural Tests 
Urine Pregnancy Test (female 
subjects only) 
Eligibility assessment 
X 
X 
 
Urine Drug Screen 
Assessment of illicit drug use 
X 
X 
 
Electrocardiogram (ECG; 
subjects on methadone only) 
Assessment of cardiac function 
X 
 
 
* Vital signs (blood pressure, pulse, respiratory rate, and pulse oximetry) will be obtained prior to treatment sessions and at 60 minutes post-treatment.  
Temperature will be monitored immediately prior to treatment.  If there is an increase in systolic or diastolic blood pressure >30 mm Hg from baseline, or 
an increase in pulse rate >30 bpm from baseline, subjects will be treated with standard of care antihypertensive medications (i.e. clonidine) and the 
measurements will be repeated every 20 minutes until BP and pulse are within 30 points of the baseline values.   
 
7.4 Baseline Assessment Procedures 
After completing study informed consent, participants will undergo a comprehensive evaluation to assess 
for inclusion and exclusion criteria.  This will include self-reports and clinician assessments as shown in 
Table 1.  This will also include assessment of depression severity and participants at highest risk for 
suicidality based on clinician assessment, those with a self-reported suicide attempt within the past year, 
and those felt likely to require hospitalization during the course of the study will be excluded. The 
comprehensive exam will also include a history and physical exam by the study PI (pulse oximetry 
measurements will be a component of the respiratory evaluation) and baseline medication evaluation for 
potential harmful interactions.  Urine pregnancy tests will be completed for every woman of childbearing 
potential. Urine drug screening will be collected at baseline and prior to each ketamine session to monitor 


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for opioid and other illicit substance use. For patients currently taking methadone, ECG will be performed 
to assess for cardiac function with QTc interval of 450ms or longer being exclusionary. Assessments may 
be conducted by telehealth with vital signs to be provided by participant’s home or pharmacy 
measurement. 
 
 
7.5 Intervention Visit Procedures 
Prior to administration of the study compounds, participants will complete self-report questionnaires and 
clinical assessments.  The study physician will disinfect the subject’s shoulder using an alcohol wipe, 
and the study physician will then administer the medication by intramuscular administration into the 
participant’s deltoid muscle.  Vital signs will be monitored prior to treatment, and at 60 minutes post-
treatment.  If during the post-administration observation period, ketamine administration causes an 
increase in systolic or diastolic blood pressure >30 mm Hg from baseline, or an increase in pulse rate 
>30 bpm from baseline, the subject will be treated with standard of care antihypertensives (i.e. 
clonidine), and repeat vital sign measurements will be taken approximately every 20 minutes until blood 
pressure and pulse are within 30 points of baseline values. Standard of care antihypertensive 
medications will be procured via intrainstitutional transfer from MUSC investigational drug services 
pharmacy distribution center. They will be stored in a DHEC compliant locked box within a locked room 
accessible only to study team members. If the subject experiences symptoms of hypertensive 
emergency, the subject will not receive further administration of ketamine and will be withdrawn from the 
study.  After completion of the injection, participants until returned to baseline per clinical assessment 
which time they will undergo debriefing and complete assessments of their perceptual experience of the 
intervention.  We will evaluate the effects of a weekly interventions for 8 sessions. Participants will return 
for follow-up assessment 1, 2, 4 and 8 weeks following final medication session. Follow-up visits may be 
conducted by telehealth. 
 
8.0 
DATA MANAGEMENT 
8.1 Data Analysis Plan 
Baseline demographic characteristics will be collected, and descriptive statistics will be used to 
characterize participants. Data will be collected and managed using the secure REDCap (Research 
Electronic Data Capture) database. 
 
8.2 Data Confidentiality Procedures 
We will take rigorous precautions to maintain confidentiality for all participants, using procedures that the 
PI and his mentors have successfully employed in similar previous, as well as ongoing related studies.  
All study data related to mental health outcomes (i.e., the participant responses to questionnaires) and 
demographics will not have any unique identifying data attached.  There will be only one master list of 
participants (not linked to participant responses).  This list will be kept locked separate from other data 
and will be available only to the PI, his mentors, and approved study personnel.  All data will be 
confidentially stored (i.e., in locked files or on encrypted servers) so as to protect the confidentiality of 
participant information. Access to research records (paper and computerized) will be restricted to the 
project staff, and to sponsor audit personnel and MUSC IRB auditors when indicated.  All study personnel 
have completed (or will complete upon hiring) a certified program of instruction in the protection of human 
subjects in research, such as the University of Miami CITI course.  These courses in the responsible 
conduct of research and the protection of human subjects will be completed on an annual basis, in 
compliance with MUSC regulations. 
 
8.3 Data Quality Control Procedures 


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Data quality will be monitored by random inspection of the completed forms by the study team and any 
irregularities or problems detected will be discussed with the PI. 
 
8.4 Study Documentation and Data Handling 
Any clinical study event that is judged to be an AE will be recorded on the AE form during the course of 
the study. The PI and/or trained Research Assistant will ensure this information is captured during every 
study visit.  Whenever a study participant has reported an AE, the study coordinator will discuss the event 
immediately with the PI (if possible while the study participant is there) who will evaluate the event.  If the 
AE is not serious, the information will be recorded, managed medically as appropriate, and the event will 
be followed until resolution. SAEs will also be recorded on the AE Form, managed medically as 
appropriate, and the event is followed until resolution.  In addition, the PI will review all completed AE 
forms for determination of SAE. All SAE reports will be sent to the MUSC IRB within 24 hours of learning 
of event occurrence. 
 
AEs/SAEs will be documented and reported as per IRB requirements. Research staff will identify AEs and 
obtain all available information to assess severity, seriousness, study relatedness, expectedness, 
outcome and the need for change or discontinuation in the study intervention.  Adverse events will be 
documented on AE Logs and additional relevant AE information, if available, will be documented in a 
progress note in the research record as appropriate to allow monitoring and evaluating of the AE. If the 
AE meets the definition for Serious, appropriate SAE protocol specific reporting forms will be completed 
and disseminated to the appropriate persons and within the designated timeframes as indicated above. 
For each AE/SAE recorded, the research staff will follow the AE/SAE until resolution, stabilization or until 
the participant is no longer in the study.  When a reportable SAE is identified, the research assistant will 
initiate an SAE form, and the following individuals will be notified within 24 hours of the site’s initial 
notification of the SAE:   
1. 
The PI (Dr. Dobson) will provide oversight, consultation, assessment, and documentation as 
appropriate of the SAE.    
2. 
The research staff will notify the MUSC IRB, and complete the AE report form in conjunction with 
the PI. Communication with the MUSC IRB is through email, memos, official IRB forms, and online 
reporting. 
 
If complete information is not available when the initial 24-hour SAE report is disseminated, follow-up 
information will be gathered to enable a complete assessment and outcome of the event.  This information 
may include hospital discharge records, autopsy reports, clinic records, etc.  The research staff will attach 
copies of source documents to the SAE report for the PI and for forwarding to the sponsor as appropriate.  
All deaths that occur during the study or 30 days post termination from the study are required to be 
reported as adverse events even if they are expected or unrelated.  Other adverse events are reportable 
to the MUSC IRB if the AE is unexpected AND related or possibly related AND serious or more prevalent 
than expected.  All three criteria must be met for an AE to be reported to the MUSC IRB.  The IRB definition 
of unexpected is that the AE is not identified in nature, severity or frequency in the current protocol, 
informed consent, investigator brochure or with other current risk information.  The definition of related is 
that there is a reasonable possibility that the adverse event may have been caused by the drug, device 
or intervention.   
 
8.5 Privacy Protection and Confidentiality Assurances 
While absolute confidentiality cannot be guaranteed, every possible effort will be made to protect the 
privacy of study participants, and all of the investigators have an excellent history of maintaining subject 
privacy and data security.  Participants will be provided with a written informed consent document which 
specifies the risks and confidentiality protections and limits of study procedures.  Subject names will 
remain confidential and all study data related to outcomes (i.e., the participant responses to 
questionnaires) and demographics will not have any unique identifying data attached in any way. There 


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will be only one master list of participants (again, not linked to any participant responses) which will be 
kept locked separate from all data and will be available only to the PI, Co-Is and approved study personnel.  
All data will be stored in a confidential manner (i.e., in locked files or on encrypted computers) so as to 
protect the confidentiality of participant information. Access to research records (paper and computerized) 
will be restricted to the project staff.  Access to de-identified study data will be limited to named PI, co-Is 
and MUSC IRB auditors. 
 
8.6 Data Sharing 
The data collected from study participants, including PHI, will be entered into and securely stored in the 
database on a secure server by a member of the research study team.  Electronic data will be stored, 
managed, and analyzed by the study PI and his statistical advisor. 
 
9.0 
PROVISIONS TO MONITOR THE DATA TO ENSURE THE SAFETY OF SUBJECTS  
Ongoing Clinical Monitoring: The research team will closely monitor for any increase in substance use or 
psychiatric distress at every study intervention visit.  Subjects with clinically significant worsening of 
depression (i.e. development of suicidal ideation) or worsening of opioid use will be immediately referred 
for a higher level of treatment, and the PI will review trial safety.  The PI will be responsible for assessing 
potential participants for inclusion and exclusion criteria, and for assessing for adverse effects (AE's) 
throughout the trial. AE's will collected, documented, and reported. If the AE is not serious, the information 
will be recorded, managed medically as appropriate, and the event will be followed until resolution. SAEs 
will also be recorded on the AE Form, managed medically as appropriate, and the event is followed until 
resolution.  In addition, the PI will review all completed AE forms for determination of SAE. All SAE reports 
will be sent to the MUSC IRB within 24 hours of learning of event occurrence. The PI will be responsible 
for withdrawal of a study participant if they become pregnant or feel that participation is no longer in a 
subject's best interests. Mental health symptoms will be monitored using standardized measures at each 
visit in order to detect any worsening symptoms.  Additionally, participants will be advised to observe any 
signs of worsening substance use or depression symptoms, and to discuss these with the research team.  
All participants will be informed at the initial visit that they may terminate participation at any point.  If a 
participant experiences distress or other problems between visits, he or she will be encouraged to contact 
Dr. Dobson or his/her outpatient mental health provider.  If a participant needs or desires immediate 
attention, arrangements will be made for an appointment with an experienced mental health provider.  The 
informed consent document will provide direction to contact the study staff during office hours and/or go 
to the Emergency Room at any time for worsening of symptoms.  In addition, participants will have access 
to urgent care services at MUSC.  If any of the research personnel believes that a participant is medically 
or psychiatrically compromised by participation, the PI will be notified and will contact the participant 
immediately to assess concerns and assure participant safety.  The PI will attempt to address all 
participant concerns and will set up an alternate referral for counseling for those who desire it from outside 
the project.  All participants will review, at the initiation of participation, an informed consent document 
which specifically reviews potential psychological distress as a potential outcome of participation.  If 
necessary, the participant will be asked to complete a safety plan and to call the project staff, a national 
hotline, or 911.  The Mobile Crisis unit of Charleston County, which involves a team of police and 
psychiatric workers, or the EMS unit may be dispatched to the participant’s home to assure safety.  The 
investigative team has a long history of ensuring participant safety using similar methods in these 
populations. 
 
Pre-Intervention Assessment: A comprehensive exam will be conducted as part of the baseline 
assessment to minimize risks from study participation.  This will include assessment of depression 
severity, and participants at highest risk for suicidality will be excluded. The comprehensive exam will also 
include a history and physical exam by the study PI (pulse oximetry measurements will be a component 
of the respiratory evaluation), baseline medication evaluation for potential harmful interactions, and 
electrocardiogram to ensure safe study participation.   


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Peri-Intervention Monitoring: Subjects will be continuously medically and psychiatrically monitored 
throughout the course of the intervention and until return to medical and psychiatric baseline.  Subjects 
will be instructed not to eat for at least 2 hours before taking the intervention sessions to reduce the risk 
of nausea and vomiting.  Emergency services will be contacted in the event of any medical complications.  
Subjects will not be allowed to drive themselves after the interventional visits, and alternative 
transportation will be arranged if needed. 
 
10.0 
WITHDRAWAL OF SUBJECTS 
All potential participants will be thoroughly screened for eligibility after completing informed consent.  The 
PI may withdraw subjects from participation at any time if the participant demonstrates or reports 
significant distress, is felt to be at risk of harm to themselves or to others, or is otherwise unable to 
complete the study protocol.  Referrals to university and community resources will be made as indicated 
for all participants withdrawn from the study.  The trial will be stopped under any of the following conditions: 
1) there is clear evidence of harm; 2) there is no likelihood of the intervention demonstrating benefit, or 3) 
there is overwhelming evidence of the benefit of the intervention. 
 
11.0 
RISKS TO SUBJECTS 
11.1 Overview 
All medications have potential side effects. Ketamine has been well studied since its FDA approval in 
1970.  Based on extensive prior research with intravenous ketamine in the treatment of depression, the 
prevalence of the most commonly observed adverse reactions are estimated below by category.  
Participants will be informed of potential side effects associated with ketamine before study participation, 
and will be closely monitored both during the treatment and at each follow-up visit.   
11.2 Physical Risks 
The most significant physical adverse event from ketamine is a transient increase in blood pressure, 
which in previous studies was experienced by 29.8% of subjects with a mean systolic blood pressure 
increase of 19.6 mmHg +/- 12.8 mmHg and a mean diastolic blood pressure increase of 13.4 mmHg +/-  
9.8 mmHg. Peak levels are reached on average 40 minutes post-treatment and resolve by 240 minutes 
post-treatment (Wan et al., 2015). Participants experiencing clinically significant hypertension (greater 
than 180 mmHg SBP or greater than 105 mmHg DBP, or greater than 30 mmHg SBP or DBP from 
baseline values) will be treated with standard of care hypertensives (e.g. clonidine) and monitored until 
symptom resolution.    
 
The most prevalent physical adverse effect was transient sedation and occurs in approximately 16% of 
patients receiving ketamine.  Sedation will be monitored via continuous clinical observation during 
interventional sessions.  A medical emergency team will be called for participants that are unable to be 
aroused with painful trapezius squeeze or that experience hypoxia (i.e. a pulse oximeter reading of 92% 
or less), although in the investigative team’s extensive experience using ketamine clinically for depression 
at these doses, such serious events have never occurred.  Vital signs will be routinely monitored during 
treatment and emergency airway equipment will be immediately available. Subjects will be monitored for 
2 hours post-dose by trained healthcare professionals (eg PI, co-I, or study nurse). Due to transient 
cognitive impairment associated with sedation, participants will not be allowed to drive themselves 
following the interventions. Subjects who do not have transportation and live within 20 miles will receive 
compensation for taxi, Uber or Lyft transportation to and from medication sessions up to $100 each way. 
Subjects who live greater than 20 miles from the study site and cannot arrange their own transportation 
will be excluded from the study. Participants will be advised not to operate heavy machinery for at least 
24 hours after the interventions.  
 
There are also the standard risks associated with intramuscular injections including temporary local pain, 
irritation, or redness at the site of the injection.  There is a very small (<1%) risk of infection, muscle 
fibrosis, or persistent muscle or nerve damage at the site of injection.   


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11.3 Psychological Risks 
Ketamine commonly causes transient dissociation (including derealization and depersonalization) and 
perceptual changes (e.g. distortion of time and space, sense of illusions).  Based on prior studies these 
effects occur in 42% of subjects receiving ketamine.  Anxiety occurs in 15% of subjects receiving 
ketamine.  Psychological distress will be minimized with pre-treatment relaxation exercises and 
psychological reassurance as needed.  Psychological distress will be minimized with pre-intervention 
relaxation exercises and reassurance as needed.  In prior trials with ketamine for depression, these 
measures are sufficient to manage dissociation and anxiety in the overwhelming majority of participants.  
However, standard of care medications for agitation (e.g. benzodiazepines) will be available in the event 
that participants develop severe anxiety psychological distress unmitigated by reassurance and 
relaxation exercises.  Psychiatric hospitalization will be arranged if needed, in the unlikely event of severe 
or prolonged psychiatric symptoms (e.g. lasting greater than four hours or the business day).  Participants 
may also have emotional distress from answering the questionnaires, although this is mild in the 
investigators’ experience with these instruments.   
11.4 Abuse Liability 
Ketamine is a psychoactive substance and is considered to have abuse liability.  Ketamine is classified 
as Schedule III controlled substances (CIII).  While there have been no randomized controlled trials 
evaluating the risk of subsequent illicit or recreational use of ketamine following medical administration 
(either for induction of sedation in conjunction with general anesthesia or in monitored off-label use for 
depression or pain management), in the extensive sub-anesthetic trials of ketamine for depression, there 
have been no published reports of illicit use developing after initial medical treatment with ketamine.  
None of the previous studies using ketamine in the treatment of substance use disorders reported illicit 
ketamine use following the ketamine interventions (Jones et al., 2018).  Animal models using intracranial 
self-stimulation have demonstrated that ketamine fails to progress to self-administration, also suggesting 
a lack of abuse liability.  Globally, the World Health Organization (WHO) evaluates the overall risks and 
abuse liability of ketamine; in their most recent report, the WHO affirmed that ketamine does not pose a 
global health risk, and again recommended its continued use (WHO, 2016). Substance use will be 
assessed at each visit throughout the study, and participants will be referred for ongoing care if they 
develop new or worsening substance use.  If participants report illicit use of ketamine between 
intervention sessions, they will be withdrawn and referred for substance abuse treatment.   
11.5 Social Risks: Adverse social consequences may arise if the participants’ medical history or 
psychiatric history (including substance use history as well as psychiatric comorbidities) are inadvertently 
communicated to others.   
11.6 Legal Risks: Legal risks may arise if individuals are homicidal or suicidal and make these intentions 
known to the PI project staff, who may then be required to notify authorities and the target of homicidal 
intent.  There is also a legal and physical risk if participants were to drive or operate heavy machinery 
while cognitively impaired. Subject will be advised against operating heavy machinery following 
treatment. 
11.7 Economic Risks: Subjects will be reimbursed for travel expenses including taxi, Uber or Lyft fare 
within 20 miles of study site as well as for any medical care related to study-related injuries. Subjects will 
not be compensated for medications sessions but will receive $15 for each follow-up session completed. 
11.8 Other Risks: While every possible effort will be made to protect the privacy of study participants, 
there is a risk of loss of confidentiality.  There may also be unknown risks associated with the study 
procedure or intervention. 
 
 
12.0 
POTENTIAL BENEFITS TO SUBJECTS OR OTHERS 
12.1 Potential Benefits to Subjects 
Potential benefits of participation in this study may include a reduction in depression symptoms.  
Participants may also gain diagnostic information about their medical or psychiatric comorbidities, 


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although this is not guaranteed.  Overall, there is no guarantee or promise that participants will receive 
any benefit from participation in this study.   
12.2 Justification of Risks 
The potential benefits of the knowledge to be gained from the proposed study are considerable. This study 
proposes to test intramuscular ketamine in the treatment of co-occurring OUD in early or sustained 
remission and MDD among participants. The plans for monitoring risk as described above warrant the 
conduct of this study for the knowledge that may reasonably be expected to result.  
 
13.0 
SHARING OF RESULTS WITH SUBJECTS 
The data collected from study participants, including PHI, will be entered into and securely stored in the 
database on a secure server by a member of the research study team.  Electronic data will be stored, 
managed, and analyzed by the study PI and a statistical mentor advisor.  Individual baseline data may 
be released to participants on request for their subsequent medical use or disclosure.  
14.0 
DRUGS OR DEVICES  
The IND application for ketamine’s use in this study has been submitted by PI for FDA review.   IND 
number 159117 has been issued by the FDA. Study will not begin until a Study May Proceed letter is 
received from the FDA. Medication and placebo will be stored in lock boxes on the MUSC campus and 
be administered by the PI or   co-I. 
 
15.0 
REFERENCES 
 
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Long,  and at What Frequency? The Journal of Clinical Psychiatry, 78(7), e852–e857. 
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Azhari, N., Hu, H., O’Malley, K. Y., Blocker, M. E., Levin, F. R., & Dakwar, E. (2021). Ketamine-
facilitated behavioral treatment for cannabis use disorder: A proof of  concept study. The American 
Journal of Drug and Alcohol Abuse, 47(1), 92–97. https://doi.org/10.1080/00952990.2020.1808982 
Baer, R. A., Smith, G. T., Hopkins, J., Krietemeyer, J., & Toney, L. (2006). Using self-report assessment 
methods to explore facets of mindfulness. Assessment, 13(1), 27–45. 
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Barrett, F. S., Johnson, M. W., & Griffiths, R. R. (2015). Validation of the revised Mystical Experience 
Questionnaire in experimental sessions  with psilocybin. Journal of Psychopharmacology (Oxford, 
England), 29(11), 1182–1190. https://doi.org/10.1177/0269881115609019 
Beck, A. T., Steer, R. A., & Brown, G. K. (1996). Manual for the Beck Depression Inventory-II. San 
Antonio, TX: Psychological Corporation. 
Blevins, C. A., Weathers, F. W., Davis, M. T., Witte, T. K., & Domino, J. L. (2015). The Posttraumatic 
Stress Disorder Checklist for DSM-5 (PCL-5): Development and  Initial Psychometric Evaluation. 
Journal of Traumatic Stress, 28(6), 489–498. https://doi.org/10.1002/jts.22059 
Bohnert, K. M., Ilgen, M. A., Louzon, S., McCarthy, J. F., & Katz, I. R. (2017). Substance use disorders 
and the risk of suicide mortality among men and women in the  US Veterans Health Administration. 
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Dakwar, E, Nunes, E. V, Hart, C. L., Hu, M. C., Foltin, R. W., & Levin, F. R. (2018). A sub-set of 
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ICF_001.pdf: 
Page 1 of 12 
Version Date: 10/6/2021 
 
IRB Number: Pro00115696 
Date Approved: 12/7/2021 
 
 
 
 
Medical University of South Carolina 
CONSENT TO BE A RESEARCH SUBJECT 
 
TITLE OF RESEARCH:  Ketamine-assisted psychotherapy for the treatment of persistent depression in 
abstinent opioid users 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concise Summary 
 
Your consent is being sought for a research study. Participation is voluntary. The purpose of the 
study is to examine whether an investigational medication called ketamine along with psychotherapy 
can improve depression in individuals with past opioid addiction who have achieved sobriety for 3 
months or more. If you are eligible and you decide to participate in the study, your participation will 
last approximately 16 weeks or 4 months.  
 
The study will involve an initial screening visit. You will complete questionnaires and interviews in a 
private room. The questionnaires and interviews will be related to your physical and mental health.  
The initial phase of the study will involve 8 weekly clinic visits. At each of these visits, you will be 
asked to answer several questionnaires and women will provide a urine sample to check for 
pregnancy. You will meet with our therapist to set goals or intentions for each session. You will then 
be administered the study medication by an injection into your shoulder muscle and will be monitored 
by a study clinician until you feel back to your usual self. Our clinician therapist will be available 
during and after treatment to discuss your experience. You will also meet with our study physician 
1, 2, 4, and 8 weeks after your final medication session. These follow-ups can be completed virtually 
(ie, via secure video software).  
 
There are risks of participating in the study that are described in this document.  The most significant 
risks include temporary high blood pressure, anxiety, and having the sensation that you are detached 
from your body or having an altered perception of time or your body.  There is also a risk of loss of 
confidentiality, although steps will be taken to minimize this risk.  Because it is not known if the study 
medication is safe in pregnancy, if you are a woman, you will complete a pregnancy test at each visit 
when medication is to be taken to be sure that you are not pregnant. 
 
Your potential benefits from participating include improvement in your symptoms of depression.  
Your alternative is not to participate in the study. Alternative treatments are available for individuals 
with symptoms of depression who have opioid use disorder including medications such as sertraline, 
fluoxetine and citalopram as well as therapy or counseling. 


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Version Date: 10/6/2021 
 
IRB Number: Pro00115696 
Date Approved: 12/7/2021 
A. PURPOSE OF THE RESEARCH 
 
You are being asked to volunteer for a research study.  Research studies are voluntary and include 
only people who choose to take part.  Please read this consent form carefully and take your time making 
you decision.  As the study doctor or study staff discusses this consent form with you, please ask 
him/her to explain any words or information that you do not clearly understand. 
 
The purpose of this study is to examine the ability of a medication called ketamine to reduce the severity 
of depression in people with a history of opioid addiction who are in recovery (also called opioid use 
disorder in remission).  Ketamine is currently approved by the Food and Drug Administration (FDA) to 
reduce pain during some surgeries. However, ketamine is considered “investigational use” in this study, 
meaning that the FDA has not approved it for the treatment of either opioid addiction or depression.  
This is a Phase II study of ketamine, meaning that it has established use for other purposes and 
researchers are now testing this medication in larger populations.  The purpose of this study is to 
evaluate the safety and effectiveness of ketamine in the treatment of depressed individuals with a 
history of opioid addiction.  You are being asked to participate because you are over 18 years of age, 
you have symptoms of depression, and you have opioid use disorder with at least 3 months of sobriety.  
 
This study is being conducted at MUSC in Charleston, SC and will involve approximately 10 
participants.  
 
B. PROCEDURES 
 
If you agree to be in this research study, the following will happen: 
1. Screening and Baseline Visit (approximately 2-3 hours in length): 
• The initial visit will involve the following: 
o Completion of written questionnaires related to your mental and physical health.  
Questionnaires will also be related your previous use of alcohol and other drugs, your 
craving levels for opioids, ways in which opioids has impacted your life (such as legal 
trouble or relationship conflicts) and your personal goals regarding your opioid use 
and depression. 
o An interview with a clinician about questions related to your physical and mental 
health. 
o A basic physical exam like what you would get at a checkup.  Your blood pressure, 
pulse, and temperature may be checked at a local pharmacy or by a home 
measurement device.   
o If you have a history of heart problems or are taking methadone, you may be asked 
to complete an electrocardiogram (EKG).  This is a test of the function of your heart 
and involves placing small adhesive pads with wires attached on your chest.  After the 
adhesive pads are placed, a monitor shows a picture of the electrical activity of your 
heart, which is printed out on paper.  This test usually takes less than 10 minutes to 
complete.  If you have had this test done within the previous sixty days at MUSC, your 


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IRB Number: Pro00115696 
Date Approved: 12/7/2021 
medical record will be reviewed. If this test was normal, you will not have to complete 
the electrocardiogram test. 
o If you have a history of liver, kidney, or blood cell-related problems, you may be asked 
to have your blood drawn.  Approximately 1 teaspoon of blood will be drawn for these 
tests to evaluate whether your liver or kidneys are working well.  The tests will also 
check whether you have any electrolyte imbalances such as abnormal sodium or 
potassium levels. The tests will also measure the levels of your blood cells, which are 
responsible for fighting infection, carrying oxygen, and forming clots when you are 
bleeding.  If you have had these blood tests done within the previous sixty days at 
MUSC, your medical record will be reviewed. If they were normal, you will not have to 
complete the blood tests.   
o A urine sample will be collected at baseline and follow-up to determine if you are using 
any drugs including opioids.  
• After staff has reviewed all the information collected, you will be contacted to inform you of 
your eligibility status.  If you are eligible to enroll and choose to continue participation, you 
will be asked to come for weekly medication visits for 8 weeks. If you are not found eligible 
and/or do not choose to continue in the study, additional community resources can be made 
available to you upon request.   
• If you are a woman of childbearing potential and/or a man capable of fathering a child, 
precautions should be taken throughout the course of the medication phase of the study. 
Examples of acceptable methods of birth control for participants involved in the study 
includes: birth control pills, patch, IUD, condom, sponge, diaphragm with spermicide, or 
avoiding sexual activity that could cause you to become pregnant. In addition, urine 
pregnancy tests will be completed at baseline visit. If you are pregnant, you will be withdrawn 
from the study. 
2. Medication Visits (approximately 2-3 hours each in length): 
• If you are eligible and decide to participate in the study, over the next 8 weeks you will come 
to the study center once per week to complete the medication visits.  You will be encouraged 
to come well hydrated, but in a fasting state (i.e. not having eaten for 2 hours prior to the 
treatment visit).  At these visits, you will complete questionnaires and urine testing much like 
the ones completed at the screening visit.  These tasks will take about 30 minutes.   
• You will complete a urine pregnancy test prior to each medication session (only if you are a 
woman of childbearing potential).  The urine pregnancy test must be negative to participate. 
 
• Each medication visit will include non-directive, supportive psychotherapy, which can include 
setting an intention for your session, supportive talk as needed throughout medication session, 
reflection on the experience of the session afterwards, and setting goals to work on after each 
session. 
 
• Prior to being administered the medication, you will sit in a chair and be guided by the study 
doctor through a basic relaxation exercise.  This exercise will help you to focus on your 


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Date Approved: 12/7/2021 
breathing and is designed to help reduce any anxiety you may feel related to the medication 
sessions.  The relaxation exercise will last about 10 minutes. 
• After you complete the relaxation exercise, you will have your blood pressure and heart rate 
checked, and you will have a small, painless monitoring device placed on your finger which 
will measure the oxygen levels in your blood throughout the medication session.   
• The study medication, ketamine, is given by intramuscular injection.  
• After receiving the injection, you will be instructed to rest in a chair. After approximately 90 
minutes, you will take complete several short questionnaires.   
• Your blood pressure will be checked again, and if it is normal, the blood oxygen finger device 
will be removed, and the visit will be completed.  If your blood pressure is high, you are feeling 
anxious, or you are not feeling like yourself, you will continue to be monitored by the study 
doctor until these symptoms return to normal. 
• After completing the visit, you will be asked to have someone drive you home.  If you do not 
have someone that can drive you home and live locally, transportation (such as a taxi) will 
be provided for you at no cost to you. If you live more than 20 miles from the study site and 
cannot arrange your own transportation you will not be able to participate in this study. 
3. Follow-Up Visits (approximately 30 minutes each in length): 
• Completion of written questionnaires related to your mental and physical health. 
Questionnaires will also be related to recent use of alcohol and other drugs, your cravings 
for opioids, and your recent symptoms of depression and anxiety. 
• Follow-up visits can be completed either in person or virtually (via secure video software) 
depending on your preference. 
 
C. DURATION 
 
Participation in the study will take about 13 visits over a period of approximately 4 months.  There will 
be an initial screening visit (approximately 2-3 hours), 8 study medication visits (approximately 2-3 
hours each), and 4 follow-up visits (approximately 30 minutes). 
 
D. RISKS AND DISCOMFORTS 
 
There are risks involved with participating in this study, including risks associated with ketamine, study 
procedures, and loss of confidentiality. 
 
Ketamine Risks: 
Ketamine may cause some, all or none of the side-effects listed below.  These effects are generally 
temporary and resolve within one hour, although they may last up to six hours.  A study physician will 
monitor you until these symptoms resolve.   
 


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IRB Number: Pro00115696 
Date Approved: 12/7/2021 
More Likely (10 percent to 50 percent): 
• Perceptual changes (e.g. distortion of time and space, sense of illusions) and dissociation 
(including a sense of detachment or altered sense of reality)  
• Feeling abnormal or drunk 
• Elevated blood pressure  
• Elevated heart rate 
• Anxiety 
• Sedation (sleepiness) 
• Vertigo or dizziness 
• Nausea 
• Decreased pain threshold 
   
Less Likely (5 percent to 10 percent):  
• Injection site swelling, pain, redness, or discomfort 
 
Rare (less than or equal to 5 percent): 
• Bladder discomfort or increased frequency of urination (also called cystitis) 
• Anaphylaxis 
 
Unknown risks: 
• High amounts of ketamine given to rats caused damage to different parts of the brain. It is not 
known whether this finding in rats will happen in humans. The amount of ketamine given to the 
rats was higher than what you will receive in this study. 
• The added effect of repeated ketamine infusions is unknown. Chronic ketamine users (mostly 
ketamine abusers) may have structural and functional brain changes with associated memory 
problems. We are uncertain if this will occur at the frequency and duration proposed in this study. 
• Bladder irritation and liver problems have been related to the repeated use of ketamine. We are 
uncertain if this will occur at the frequency and duration proposed in this study. 
• The study treatment may also involve other risks, which are currently unforeseeable. 
• If you become pregnant, the study treatment might involve risks to the embryo or fetus, which 
are currently unforeseeable. 
 
Clonidine Risks: 
If you experience clinically significant elevated blood pressure, you will be treated with a blood pressure 
medicaton called clonidine. Clonidine will be given by mouth. Most common clonidine side effects include 
dry mouth (40 percent), drowsiness (33 percent), dizziness (16 percent), constipation (10 percent) and 
sedation (10 percent). Syncope (or passing out) is a rare but possible side effect of clonidine.” 
 
Interviews and Surveys: The questions that will be asked may be sensitive in nature and may make 
you feel uncomfortable.  You may be asked personal questions that you find distressing. You may 
refuse to answer any question(s) that you do not wish to answer.  
 
Risks from Blood Draws: Risks associated with drawing blood from your arm include brief discomfort, 


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anxiety, and/or bruising. Infection, excess bleeding, clotting, or fainting is possible, although unlikely. 
 
Electrocardiogram (ECG): The ECG procedure may cause some mild discomfort during the placement 
and removal of the leads to and from the skin. You may also experience some local irritation, redness, 
or burning in the areas where the leads are attached. 
 
Risk of Loss of Confidentiality  
There is a risk of a loss of confidentiality of your personal information because of participation in this 
study.  Some answers you give during the research visits (like whether you use illegal drugs) may put 
you at risk if other people find out.  To keep what you say private, your study records will use a code 
number instead of your name.  We will protect your records to the extent allowed by law by keeping all 
your materials in locked file cabinets only accessible by research staff and all computer files will be 
secure password-protected files only accessed by research staff.  Your research records are kept 
separate from your other medical records. Only research staff will have access to your private 
information.  
 
Limits of Confidentiality:  
Suspected or known abuse or neglect of a child, disabled or elder abuse, or threatened violence to self 
or others may be reported to appropriate authorities. 
 
If you are or become pregnant and test positive for illegal drugs, it is a law that the South Carolina 
Department of Social Services (DSS) must be notified. You and your family will be evaluated by the 
agency. You could be ordered to mandatory drug treatment, lose custody of your children, or possibly 
be jailed. 
 
Unknown Risks: The experimental treatments may have unknown side effects. The researchers will let 
you know if they learn anything during the study that might make you change your mind about 
participating in the study.  
 
E. MEDICAL RECORDS AND/OR CERTIFICATE OF CONFIDENTIALITY 
 
If you have a medical record at MUSC, it may be reviewed to determine your study eligibility. Results 
from blood and electrocardiogram testing that you may be asked to complete for the study will be 
included in your medical record. Other information about your study participation will not be in your 
medical record.  This means that your research participation, drug and pregnancy testing, and 
responses to questionnaires will not be included in your MUSC medical record. 
 
F. BENEFITS 
 
If you receive ketamine, and it is more successful in treating your conditions compared to other 
antidepressants or types of psychotherapy, you may benefit from participating in the study.  However, 
given the investigational nature of this study, benefit cannot be guaranteed or promised.  Information 
gained from this study may help other investigators have a better understanding of the treatment of 
opioid use disorder and depression. 


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Date Approved: 12/7/2021 
 
G. COSTS 
There will be no cost to you because of participation in this study.  If you choose to receive text 
message study reminders, normal data and usage rates will apply. You will be reimbursed for 
transportation costs (ie, via Uber, Lyft, or taxi) necessary for your participation in this study if you are 
unable to secure transportation to and from study visits otherwise and live within 20 miles from the 
study site. Reimbursement will equivalent to the amount you are charged by Uber, Lyft or a taxi 
company up to $100 for each trip to or from medication visits. If you live greater than 20 miles from 
the study site and cannot arrange your own transportation you will be unable to participate in this 
study. 
 
H. PAYMENT TO PARTICIPANTS 
Initial evaluation and eight weekly medication sessions will not result in compensation other than 
reimbursement for local travel expenses. If you choose to participate in follow-up assessments 1, 2, 
4, and 8 weeks after your final medication session you will be paid $15 for each follow-up session 
completed. Payment for follow-up assessments and local travel expenses will be made using a pre-
paid debit card, called a ClinCard. It works like a bank debit card and you may use the card to 
purchase goods or services everywhere Debit MasterCard is accepted. You will be given a ClinCard 
at the beginning of the study. Each time you receive payment for participation in this study, the money 
will be added to the card, as outlined in the payment schedule above. Details of the debit card system 
are explained on an additional sheet. 
Payments that you receive from MUSC for participating in a research study are considered taxable 
income per IRS regulations.  Payment types may include, but are not limited to: checks, cash, gift 
certificates/cards, personal property, and other items of value.  If the total amount of payment you 
receive from MUSC reaches or exceeds $600.00 in a calendar year, you will be issued a Form 1099. 
 
I. ALTERNATIVES 
If you choose not to participate in this study, you could receive other treatments for your condition. The 
standard therapies for your opioid addiction include both medications (such as buprenorphine, 
methadone, and naltrexone) and counseling-based treatments (including group sessions such as 
Alcoholics Anonymous/Narcotics Anonymous and individual counseling sessions).  There are many 
standard treatments for depression including medications and therapy (both group-based therapies 
and individual therapy or counseling).  If you are currently taking any of these treatment options, you 
may continue any standard therapy. 
Withdrawal from the Study 


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Your participation in this study is voluntary.  You may refuse to take part in or stop taking part in this 
study at any time.  You should talk with the investigator in charge of this study if you decide to do this.  
Your decision not to take part in the study will not affect your current or future medical care or any 
benefits to which you are entitled.  The investigators and/or the sponsor may stop your participation in 
this study at any time if they decide it is in your best interest.  They may also do this if you do not follow 
the investigator’s instructions, or if the study is stopped by the study sponsor, the institutional review 
board (IRB), or by a regulatory agency (such as the FDA).  If your participation is ended for medical 
reasons, you will be referred to a doctor or other health professional for care.  You will be responsible 
for the cost of these services.   


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J.  DATA SHARING 
Information about you (including your identifiable private information and/or any identifiable 
biospecimens) may have all of your identifiers removed and used for future research studies or 
distributed to other researchers for future research without additional informed consent from you or 
your legally authorized representative. 
K. DISCLOSURE OF RESULTS 
 
Study data will not be shared with you to maintain confidentiality.  
 
L.  AUTHORIZATION TO USE AND DISCLOSE (RELEASE) MEDICAL INFORMATION 
 
As part of this research study, your study doctor and his/her research team will keep records of your 
participation in this study. 
 
The health information MUSC may use or disclose (release) for this research study includes 
information in your medical record, results of physical exams, medical history, lab tests or certain 
health information indicating or relating to your condition.  
 
Your study doctor and his/her research team will use and disclose (release) your health information to 
conduct this study. The health information listed above may be used by and/or disclosed (released) to 
the following, as applicable: 
 
• 
The sponsor of the study including its agents such as data repositories or contract research 
organizations monitoring the study; 
• 
Other institutions and investigators participating in the study; 
• 
Data Safety Monitoring Boards; 
• 
Accrediting agencies; 
• 
Clinical staff not involved in the study whom may become involved if it is relevant; 
• 
Parents of minor children if less than 16 years old.  Parents of children 16 years old or older 
require authorization from the child; or 
• 
Health insurer or payer in order to secure payment for covered treatment; 
• 
Federal and state agencies and MUSC committees having authority over the study such 
as: 
 
o The Institutional Review Board (IRB) overseeing this study;  Committees with 
quality improvement responsibilities;  Office of Human Research Protections; 
Food and Drug Administration;  National Institutes of Health or Other 
governmental offices, such as a public health agency or as required by law. 
 
Those persons who receive your health information may not be required by Federal privacy laws 
(such as the Privacy Rule) to protect it and may share your information with others without your 
permission, if permitted by laws governing them.   You do not have to sign this consent form.  If you 


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choose not to sign, it will not affect your treatment, payment or enrollment in any health plan or affect 
your eligibility for benefits.  However, you will not be allowed to be a participant in this research study. 
 
You will be given a copy of this consent form.  Your authorization will expire at the conclusion of this 
study or, if you are participating in a study designed for the development of a drug or device, your 
authorization will remain in effect until the drug or device is approved by the FDA or until the 
company’s application to study the drug/device is withdrawn.   You have the right to withdraw your 
agreement at any time.  You can do this by giving written notice to your study doctor.  If you withdraw 
your agreement, you will not be allowed to continue participation in this research study.  However, the 
information that has already been collected will still be used and released as described above.  You 
have the right to review your health information that is created during your participation in this study.  
After the study is completed, you may request this information. 
 
Your health information will be used or disclosed when required by law.  Your health information may 
be shared with a public health authority that is authorized by law to collect or receive such information 
for the purpose of preventing or controlling disease, injury or disability and for conducting public 
health surveillance, investigations or interventions.  No publication or public presentation about the 
research study will reveal your identity without another signed authorization from you.   
 
If you have questions or concerns about this Authorization or your privacy rights, please contact 
MUSC’s Privacy Officer at (843) 792-8740.   
 
Regulations require that you be given a copy of the MUSC Notice of Privacy Practices (NPP) 
describing the practices of MUSC regarding your health information. One can be found at the end of 
this form. 
 
 
M. SIGNIFICANT NEW FINDINGS 
 
If there are significant new findings during the study, you will be notified. 
  
 
N. STUDENT PARTICIPATION 
 
Your participation or discontinuance will not constitute an element of your academic performance, 
nor will it be a part of your academic record at this Institution.  
 
O. EMPLOYEE PARTICIPATION 
 
Your participation or discontinuance will not constitute an element of your job performance or 
evaluation, nor will it be a part of your personnel record at this Institution. 
 
P. CLINICALTRIALS.GOV  


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A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This Web site will not include information that can identify you. At most, the Web site will include 
a summary of the results. You can search this Web site at any time. 
 
Q. COLLECTION OF SPECIMENS 
 
Blood and urine specimens may be collected in this study. Blood samples may be taken as part of the 
initial visit and will not be stored.  Results of the blood test may be made a part of your MUSC medical 
record. Urine samples from females will be checked for pregnancy at the baseline visit and every 
medication visit. Results of urine testing will not be made a part of your medical record. These 
specimens will be used solely as part of this research study and will not be shared with other 
investigators or used for commercial profit.  All specimens will be coded with your numeric study code 
to protect your confidentiality. 
R. FUTURE CONTACT 
The researcher in charge of this study might like to contact you in the future about other research 
opportunities. Please initial by your choice below for paper consents, or scroll down to the bottom of 
the screen and select your choice electronically:  
____Yes, I agree to be contacted  
____No, I do not agree to be contacted  
You have the option of receiving appointment reminders and link to study surveys through text 
messages.  Should you elect to receive text messages, normal cellular data usage and rates will apply. 
Please initial by your choice below for paper consents, or scroll down to the bottom of the screen and 
select your choice electronically:  
____Yes, I agree to be contacted via text message 
____No, I do not agree to be contacted via text message 
Results of this research will be used for the purposes described in this study. This information may be 
published, but you will not be identified. Information that is obtained concerning this research that can 
be identified with you will remain confidential to the extent possible within State and Federal law. The 
sponsor and the Food and Drug Administration (FDA) will receive copies of the research records. The 
investigators associated with this study, employees of the sponsor, the FDA, and the MUSC Institutional 
Review Board for Human Research will have access to identifying information. All records in South 
Carolina are subject to subpoena by a court of law. 
 
In the event of a study related injury, you should immediately go to the emergency room of the Medical 
University Hospital, or in case of an emergency go to the nearest hospital, and tell the physician on call 


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that you are in a research study. They will call your study doctor who will make arrangements for your 
treatment. If the study sponsor does not pay for your treatment, the Medical University Hospital and the 
physicians who render treatment to you will bill your insurance company. If your insurance company 
denies coverage or insurance is not available, you will be responsible for payment for all services 
rendered to you. 
 
Your participation in this study is voluntary. You may refuse to take part in or stop taking part in this 
study at any time. You should call the investigator in charge of this study if you decide to do this. The 
data collected on you to this point remains part of the study database and may not be removed. Your 
decision not to take part in the study will not affect your current or future medical care or any benefits 
to which you are entitled. 
 
The investigators and/or the sponsor may stop your participation in this study at any time if they decide 
it is in your best interest. They may also do this if you do not follow the investigator’s instructions. 
 
Volunteers Statement 
I have been given a chance to ask questions about this research study. These questions have been 
answered to my satisfaction. If I have any more questions about my participation in this study or study 
related injury, I may contact the investigator in charge of the study at (843) 876-1193.  I may contact 
the Medical University of SC Patient and Family Care Liaison (843) 792-5555 concerning medical 
treatment. 
 
If I have any questions, problems, or concerns, desire further information or wish to offer input, I may 
contact the Medical University of SC Institutional Review Board for Human Research IRB Manager or 
the Office of Research Integrity Director at (843) 792-4148. This includes any questions about my rights 
as a research subject in this study. 
 
I agree to participate in this study. I have been given a copy of this form for my own records.  Please 
sign below. 
 
 
________________________________________     
Signature of Participant                                Date   
 
 
  
________________________________________     
Printed Name of Participant                          Date   
 
________________________________________     
 
Signature of Person Obtaining Consent       Date