Clinical trial NCT05796791
Conditions: Tobacco Use Smoking Cessation Nicotine Dependence
Sponsor: Medical University of South Carolina
Start date: 2023-05-02; Completion date: 2024-06-30
Enrollment: 7 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of the study is to examine whether an investigational medication called ketamine is able to improve treatment outcomes for tobacco use disorder when delivered in conjunction with brief motivational enhancement therapy. Participants will receive ketamine assisted motivational enhancement therapy weekly for three weeks and there will be 2 follow up visits. All visits will also consist of questionnaires and saliva samples will be taken. The overall participation will last approximately 8 weeks.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: Ketamine Hydrochloride intervention 2: Motivational enhancement therapy
Intervention descriptions: intervention 1: IM ketamine given in weekly session for a total of 3 weeks intervention 2: Brief motivational based therapy

Protocol documents:
Prot_SAP_001.pdf: 
PROTOCOL TITLE: Ketamine-assisted Motivational Enhancement Therapy for the Treatment of 
Tobacco Use Disorder 
 
PRINCIPAL INVESTIGATOR:  
Emily C. Amador, DO 
 
 
 
 
 


PROTOCOL TITLE: Ketamine-assisted Motivational Enhancement Therapy for the Treatment of 
Tobacco Use Disorder  
 
Version Date: February 28, 2023 
 
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TABLE OF CONTENTS 
1. BACKGROUND ………………………………………………………………………………………… 4 
1.1. 
Introduction and Context 
1.2. 
Current treatment for Smoking Cessation  
1.3. 
Clinical Trials for Substance Use Including Ketamine-Assisted Therapies 
1.4. 
The Neurobiology of Tobacco Use Disorder  
1.5. 
Innovation and Importance of the Current Study 
2. PURPOSE……………………………………………………………………………………….………. 6 
2.1. 
Purpose and Objectives of the Study 
2.2. 
Specific Aims 
3. STUDY DESIGN/METHODS ………………………………………………………………………….. 7  
3.1. 
Study Overview 
3.2. 
Duration of Treatment and Study 
3.3. 
Description of Assessments 
3.4. 
Schedule of Assessments 
3.5. 
Baseline Assessment Procedures 
3.6. 
Intervention Visit Procedures 
4. INTERVENTIONAL PRODUCT………………………………………………………………………. 10 
4.1. 
Overview of Study Medication 
4.2. 
Safety and Toxicity 
4.3. 
Study Drug, Dose, Mode of Administration and Justification 
5. INCLUSION AND EXCLUSION CRITERIA/STUDY POPULATION ……………………………. 10 
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. STUDY ENDPOINTS …………………………………………………………………………………. 11 
6.1. 
Primary Outcomes 
6.2. 
Secondary Outcomes 
6.3. 
Exploratory Outcomes 
7. CONSENT…………….……………………………………………………………………………….   13 
7.1. 
Qualifications of Study Personnel Obtaining Informed Consent and Capacity of 
Participants 
7.2. 
Location of Informed Consent 
7.3. 
Method of Obtaining Consent 
7.4. 
Capacity of Participants to Give Informed Consent 
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 
9. PROVISIONS TO MONITOR THE DATA TO ENSURE THE SAFETY OF SUBJECTS ……. 15 


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10. WITHDRAWAL OF SUBJECTS ……………….……………………………………………………. 16 
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 ……………….………………………… 18 
16.1. Potential Benefits to Subjects 
16.2. Justification of Risks 
13. SHARING OF RESULTS WITH SUBJECTS ……………………….……………………………... 18 
14. DRUGS OR DEVICES …………………………………….………….……………………………... 18 
14.1. Preparation, Handling and Storage of Study Medication 
14.2. Investigational New Drug (IND) Data 
15. REFERENCES ……………….………………………………………………………………………. 18 
 
 


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1.0 BACKGROUND 
1.1 Introduction and Context 
Tobacco use causes more than 7 million deaths per year worldwide (WHO, 2022) and continues to be 
the leading modifiable risk factor for cancer globally (Tran et al., 2022). In the United States, it remains 
the single largest preventable cause of disease, disability, and premature death with an estimated life 
expectancy of 10 years shorter than that of a non-smoker. Unfortunately, in the year 2020, 12.5% of 
U.S. adults (30.8 million people) continue to smoke cigarettes (CDC, 2022 Aug) despite the multiple 
smoking cessation treatments available. While the forms of tobacco use are changing, such as the 
increasing use of e-cigarettes, a 2019 study showed cigarettes remain the most commonly used 
tobacco product (CDC, 2020). 
 
Among individuals who currently smoke cigarettes, over 2/3 (68%) have reported a desire to quit (CDC, 
2022 Mar). In 2018, 55.1% of smokers reported making at least one quit attempt in the past year, 
however, only 7.5% of people who tried to quit succeeded (CDC, 2022 Mar). Overall, those who use 
smoking cessation therapies, such as counseling and medications, had a higher success rate than 
those who did not. For example, abstinence rates were 15% in people who used assistance versus 7% 
in those who did not at 12 month follow up (Shu-Hong, 2000), however, the rate of sustained abstinence 
continues to be low (Babb et al., 2017). While the proven benefit of both non-pharmacological and 
pharmacological therapy in many patients is encouraging, there is a need for additional treatments. 
 
1.2 Current treatment for smoking cessation 
There have been many studies showing the benefit of pharmacologic treatment in the assistance of 
smoking cessation. While the proportion of smokers who benefit from smoking cessation medications 
decreases during the first year of use, a net benefit remains at 12 months. Specifically, a meta-analysis 
reported an abstinence rate of 20% in people who attempted smoking cessation with medications 
versus 11% without medications at 12 months (Rosen et al., 2018). Common medications studied 
include nicotine replacement therapy (NRT), varenicline, and certain antidepressants. These 
medications have a variety of mechanisms proposed to treat the associated nicotine dependence of 
cigarette smoking. Varenicline is classified as a selective nicotinic receptor partial agonist, a pathway 
thought to affect the release of dopamine in the midbrain. A meta-analysis showed varenicline having a 
two- to threefold increase chance of successful long-term smoking cessation compared with 
pharmacologically unassisted quit attempts (Cahill et al., 2012). The most common antidepressant 
studied for smoking cessation is bupropion. Nortriptyline has also shown to be efficacious, however, 
serotonin reuptake inhibitors have not been shown to be helpful (Hughes et al., 2004). Bupropion has 
dopaminergic and noradrenergic activity while nortriptyline has relatively weak dopaminergic but 
significant noradrenergic activity. A Cochrane review showed bupropion doubles the odds of quitting 
smoking (Hughes et al., 2004). NRT replaces the form of nicotine by acting on the same nicotinic 
receptors as cigarettes, showing to be helpful when compared to no treatment. A Cochrane review 
reported NRT helps to increase the rate of quitting by 50-70% (Stead et al., 2012). When comparing 
these medications, there have been studies showing more participants quitting successfully with 
varenicline than with bupropion but limited studies comparing varenicline to NRT. There have been a 
small number of studies directly comparing bupropion with NRT with some heterogeneity but tend to 
favor bupropion (Hughes et al., 2004). This may suggest that if varenicline is more efficacious than 
bupropion, it may also more efficacious than NRT. 
 
Behavioral treatments have also been shown to increase quit rates at 6 months even in the abstinence 
of pharmacotherapy. Specific interventions include, but are not limited to, motivational interviewing, 
CBT, and mindfulness-based therapy. A Cochrane review showed motivational interviewing resulted in 
improved quit rates when compared to brief advice (Lindson-Hawley et al., 2015). When looking at 
mindfulness-based therapy, a meta-analysis concluded it did not have a significant improvement in 
abstinence over other behavioral interventions (Maglione et al., 2017). A Cochrane review looking at 


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various interventions showed benefit with any form of counseling (Hartmann-Boyce at al., 2021) and 
there has been no current consensus favoring one form of behavioral intervention. Additionally, when 
combining the results of studies in a meta-analysis, individual counseling compared to minimal 
intervention could increase the chance of quitting by 50-80% (Lancaster & Stead, 2017). 
 
It is well established that pharmacotherapy and non-pharmacotherapy can both individually help with 
smoking cessation, however, combining pharmacotherapy and behavioral support has shown to further 
increase smoking cessation success (Patnode et al., 2021; Stead et al., 2016; Lancaster & Stead, 
2017). Combined pharmacotherapy and behavioral intervention improved quit rates from an average of 
8.6% in those receiving usual care to 15.2% (Patnode et al., 2021). While these interventions can have 
substantial clinical benefit, the rate of people who continue to smoke indicates a need for novel 
treatments.  
 
1.3 Clinical trials for substance use and the rational for treatment with ketamine 
Ketamine has shown early evidence of efficacy in the treatment of multiple types of substance use 
disorders. One study evaluating the adjunctive use of ketamine in heroin use disorder showed that a 
single-session of high-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 (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% (Krupitsky et al., 2007). Related studies found that 
ketamine is useful as an adjunct to psychotherapy in the treatment of alcohol use disorder (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. Additionally, motivational 
enhancement therapy combined with just one ketamine infusion was shown to improve likelihood of 
abstinence from alcohol when compared to midazolam (Dakwar et al., 2020). Ketamine has also been 
studied in cocaine use disorder and found to improve levels of motivation to quit using and reduce cocaine 
craving (Dakwar et al., 2014) as well as reduce rates of cocaine self-administration by 67% relative to 
baseline (Dakwar et al., 2017). When ketamine was combined with mindfulness-based relapse 
prevention therapy for cocaine use disorder, it was shown that 48% of subjects who had the addition of 
one ketamine infusion were abstinent after 2 weeks compared to 10% of those who received a midazolam 
infusion (Dakwar et al., 2019). The benefit of ketamine treatment across several different substance use 
disorders as well as the synergistic effect of adding ketamine to various methods of psychotherapy 
suggests there may be an underlying mechanism and therefore a role for ketamine in the treatment of 
other substance use disorders such as tobacco dependence.  
 
1.4 The neurobiology of tobacco use dependence  
While there are about 9000 chemicals in cigarette smoke, nicotine is the major psychoactive ingredient 
and the component most associated with tobacco dependence. There are multiple proposed underlying 
mechanisms leading to nicotine dependence that current smoking cessation medications have targeted, 
including both the sensitization of nicotinic receptors in the ventral tegmentum area (VTA) after a period 
of abstinence as well as conditioned stimuli throughout the day after the nicotinic receptors have been 
desensitized (Fagerström & Balfour, 2006). The main areas of study have involved the mesocorticolimbic 
dopamine system, specifically the VTA projecting to the nucleus accumbens (NAc). Nicotine stimulates 
the mesocorticolimbic dopamine system via nicotinic acetylcholine receptors in the VTA causing 
increased firing of dopamine in the NAc (Mahajan et al., 2021). However, preclinical studies have also 
shown other critical interactions contributing to nicotine dependence with influences not only of dopamine 
and acetylcholine but also glutamate and GABA in the limbic system, prefrontal cortex, amygdala, and 
hippocampus (Markou, 2008). There is also another neurobiological pathway thought to be involved in 
aversive processing and nicotine withdrawal. This consists of the projection from the medial habenula to 


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the interpeduncular nucleus with major neurotransmitters being acetylcholine, glutamate, and substance 
P and could potentially have a role in limiting drug intake (Fowler et al., 2019). Furthermore, tobacco 
smokers have shown to have both structural and functional connectivity changes within the brain. For 
example, smoking can reduce gray matter volume in the orbitofrontal circuit (Li et al., 2015) and nicotine 
can temporarily increase fMRI signal in the striato-thalamo-orbitofrontal circuit (Bruijnzeel et al., 2015). 
The underlying mechanisms of these changes are multifactorial and likely involve multiple frontal-cortical 
inhibitory and excitatory balancing systems involved in nicotine dependence. While there has been past 
focus on the development of smoking cessation medications targeting the nicotinic system and 
dopaminergic system, the complexity of nicotine dependence shows there are other potential 
neurobiological targets for pharmacologic intervention. 
 
1.5 Innovation and Importance of the Current Study  
There are promising results in past studies of ketamine in the treatment of other substance use 
disorders (Krupitsky et al., 2002; Krupitsky et al., 2007; Dakwar et al., 2014; Dakwar et al., 2017). Given 
these studies, the neurobiological similarity between various substance use disorders (Uhl et al., 2019), 
and the potential influences of ketamine on the underlying neurological circuitry (Ezquerra-Romano et 
al., 2018), it would be beneficial to assess the role of ketamine in nicotine dependence. There has been 
one animal study showing reduction of nicotine self-administration in rats given ketamine, suggesting 
there may be an underlying mechanism of ketamine helpful in reducing nicotine use (Rezvani et al., 
2018), however, there are currently no past studies in humans studying the effects of ketamine on 
smoking cessation. 
  
 
2.0 PURPOSE/SPECIFIC AIMS 
2.2 Purpose and Objectives of the Study 
The primary objective of the proposed study is to preliminarily explore the feasibility, efficacy, and 
tolerability of ketamine in the treatment of tobacco use disorder associated with cigarette use. We seek 
to enroll 8 individuals with tobacco use disorder who use cigarettes. 
 
2.3 Specific Aims 
To achieve these objectives, the following Specific Aims are proposed: 
• 
Specific Aim 1: To assess the feasibility of using ketamine-assisted brief motivational 
enhancement therapy in the treatment of cigarette smoking cessation 
• 
Specific Aim 2: To preliminarily explore the efficacy, safety, and tolerability of ketamine-
assisted brief motivational enhancement therapy for smoking cessation 
 
 
 


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3.0 STUDY DESIGN/METHODS 
3.1 Study Overview 
This is an open label trial of ketamine-assisted psychotherapy to assess the efficacy and safety of weekly 
intramuscular injections of ketamine in the assistance of smoking cessation. This will be determined by 
evaluating the severity of craving as well as the number of cigarettes smoked the week prior to each 
session and at each follow up. 
 
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. 
 
 
3.2 Duration of Intervention and Study 
Participants will complete a total of 6 study visits (including baseline assessment and follow-up 
assessments) as shown in Table 1.  Medication sessions with intramuscular ketamine will occur weekly 
for three weeks. Participants will meet virtually or in person for follow-up at 4 and 8 weeks following final 
medication session. 
 
3.3 Description of Assessments 
For full description of assessments, see exploratory outcomes (section 6.3). 
 
3.4 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 1-3 
(Wk 1-3) 
Follow-up 
(Wk 4, 8) 
Self-Reports and Consents 
 
Informed Consent 
Obtain informed 
consent 
X 
 
 
Demographics Form 
Sample 
characterization 
X 
 
 
General Anxiety 
Disorder 
(GAD-7) 
Self-report of anxiety 
symptom 
severity 
X 
X 
X 
Insomnia Severity 
Index (ISI) 
Measure of insomnia 
severity 
X 
X 
X 
Mystical Experiences 
Questionnaire (MEQ) 
Measure of perceptual 
experiences 
X 
X 
X 
Five Facets of 
Mindfulness (FFMQ) 
Assess aspects of 
mindfulness related 
X 
X 
X 
Fagerstrom Test of 
Nicotine 
Dependence (FTND) 
Measure of nicotine 
dependence 
X 
X 
X 
Questionnaire on 
Smoking Urges 
(QSU) 
Assessment of 
smoking cravings 
X 
X 
X 
Wisconsin Smoking 
Withdrawal Scale 2 
(WSWS2) 
Measures severity of 
smoking withdrawal 
X 
X 
X 
Timeline Follow-
Back (TLFB) 
Measure of substance 
use 
X 
X 
X 
Rhode Island 
Change Assessment 
(URICA) 
Measure of stage of 
change 
X 
X 
X 
Beck Depression 
Inventory (BDI-II) 
Self-report of 
depression symptom 
severity 
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* 
 
Pre-screening 
Questionnaire 
To assess for basic 
eligibility criteria 
before completing a 
full baseline visit. 
X 
 
 
 


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Urine Pregnancy 
Test (female 
subjects only) 
Eligibility assessment 
X 
X 
 
Electrocardiogram 
(ECG; subjects with 
cardiac comorbidities 
or on QTc prolonging 
medications only) 
Assessment of cardiac 
function 
X 
 
 
Urine Drug Screen 
Assess for use of 
psychoactive 
substances 
X 
 
 
Salivary cotinine 
level 
Assessment of 
smoking status 
X 
X 
X  
* Vital signs (blood pressure, pulse, respiratory rate, and pulse oximetry) will be obtained pre- and post- 
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.   
 
3.5 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.  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 at the initial assessment and prior to each treatment session. Urine drug screens 
will be completed for all participants at the initial assessment to detect use of recreational psychoactive 
substances other than nicotine. Saliva cotinine levels will be measured at baseline, prior to each ketamine 
session and at 3 month follow up to detect smoking over approximately the previous 6 days. An ECG will 
be performed in participants with QTc interval of 450ms or longer in males or 460ms in females being 
exclusionary.  
 
3.6 Intervention Visit Procedures 
Prior to administration of the study compounds, participants will complete self-report questionnaires and 
clinical assessments.  Motivational enhancement therapy will be provided before and after ketamine 
administration, where the reduction of cigarettes and the subject’s short and long term smoking-related 
goals will be discussed with the study physician. The study physician will then 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. Only individuals who are properly 
licensed will perform the injection of ketamine. Vital signs will be monitored prior to treatment and 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 a standard of care antihypertensive (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. Medications 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 be treated with standard of care antihypertensive agents and 
referred for further assessment and treatment.  Subjects experiencing serious adverse effects related to 
study participation will not receive further administration of ketamine and will be withdrawn from the study.  
After completion of the injection, when participants return to their neurocognitive baseline per clinical 


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assessment, they will complete assessments of their perceptual experience of the intervention.  We will 
evaluate the effects of the 3 weekly interventions in 2 follow up sessions. Participants will return for follow-
up assessments 4 and 8 weeks following final medication session. Follow-up visits may be conducted by 
telehealth. If the follow up is done via telehealth, participants will be given their saliva cotinine tests in 
advance either at an in person visit or by mail and asked to return them by mail. 
 
4.0 
INTERVENTAL PRODUCTS  
4.1 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).   
 
4.2 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 
peak score of 4.5 on the Brief Psychotic Rating Scale is consistent with very mild symptom severity (Wan 
et al., 2015). 
 
4.3 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 0.71mg/kg. The participants will be weight for proper injection dosage at each treatment 
visit. This dose of 0.71mg/kg is consistent with previous studies using intravenous ketamine showing 
improvement in substance use (Dakwar et al., 2020; Dakwar et al., 2019). Recent studies have also shown 
that intramuscular ketamine may be as effective as intravenous ketamine when studied for depression 
and may be more practical clinically (Chilukuri et al., 2014; Xu et al., 2016). When given intramuscularly, 
ketamine has a peak time of 5-30 minutes following injection and a bioavailability of 86-97% (Grant et al., 
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). 
 
 
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 self-
reported current tobacco use 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: 


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1. 21 to 65 years old. 
2. Able to provide informed consent.  
3. Be a daily cigarette smoker with multiple unsuccessful previous quit attempts, and report a 
continued desire to quit smoking. 
4. Agree to abstain from smoking for the ketamine session from 1 hour before ketamine 
administration 
5. Agree to refrain from using any psychoactive drugs, including alcoholic beverages, within 24 
hours of ketamine administration. Exceptions include caffeine and nicotine. 
6. Subjects taking other psychotropic medications must be maintained on a stable dose for at least 
four weeks before study initiation.  
7. Be healthy as determined by screening for medical problems via a personal interview, a medical 
questionnaire, a physical examination, an electrocardiogram (ECG) to verify normal QTc intervals. 
8. Subjects with normal blood pressure not on antihypertensive medications or medication controlled 
hypertension as defined baseline visit systolic blood pressure (SBP) <140 mmHg or a diastolic 
blood pressure (DBP) <90 mmHg. 
 
5.3 Exclusion Criteria 
Subjects will be excluded from the study if any of the following criteria apply: 
1. Women who are pregnant (positive pregnancy test) or nursing, or are not practicing an effective 
means of birth control which can include oral, implant, intrauterine device, or patch contraceptive 
methods as well as barrier contraceptive methods, history of surgery such as hysterectomy or 
tubal ligation, or abstinence 
2. Subjects who meet DSM-5 criteria for current or history of psychotic spectrum disorders or 
current depression or bipolar disorder based on clinical interview.   
3. Subjects meeting DSM-5 criteria for current substance use disorder other than tobacco use 
disorder. 
4. Subjects with hypertension as defined by a baseline visit systolic blood pressure (SBP) >140 
mmHg or a diastolic blood pressure (DBP) >90 mmHg.  
5. A history of allergic or other adverse reaction to ketamine (or its excipients). 
6. 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). 
7. Cardiovascular conditions: uncontrolled hypertension, angina, a clinically significant ECG 
abnormality (e.g., atrial fibrillation), TIA in the last 6 months, stroke, peripheral or pulmonary 
vascular disease 
8. Subjects who live greater than 20 miles from the study site and cannot arrange their own 
transportation will be excluded from the study.   
9. Subjects with clinically significant kidney or liver impairment.   
10. Have any current neurological illnesses including, but not limited to, seizure disorders, frequent 
migraines or on prophylaxis, multiple sclerosis, movement disorders, history of significant head 
trauma, or CNS tumor. 
11. Morbidly obese (BMI >40), or severely underweight as determined by medical examination. 
 
5.4 
NUMBER OF SUBJECTS 
Approximately 8 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 


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Recruitment will be conducted through online (i.e. craigslist) and flyer advertisements throughout the 
hospital and outpatient clinics at MUSC, for example primary care clinics, relevant pulmonology clinics, 
smoking cessation clinic. 
 
Initial screening eligibility will be conducted by the PI or trained research personnel.  Subjects with self-
reported current tobacco use will be eligible to complete informed consent and baseline evaluation. 
 
 
6.0 STUDY ENDPOINTS  
6.1 
PRIMARY OUTCOMES 
• 
The primary outcome of this study will be the feasibility of using ketamine-assisted treatment for 
smoking cessation, which will assess the number of people selected for randomization that complete 
the full treatment. This will help determine if the treatment of ketamine in tobacco use would be 
beneficial for further study. 
6.2   
SECONDARY OUTCOMES 
• 
Saliva cotinine levels will be collected prior to each ketamine session and at each follow up to 
detect smoking over approximately the past 6 days. Salivary cotinine levels of <15ng/mL have 
been considered as biological verification of non-smoking status (Benowitz et al., 2020)  
• 
Time-line Follow Back (TLFB) (Sobell & Sobell, 1992) will be assessed at baseline, each treatment 
session, and at follow-ups. TLFB is a self-report calendar completed retrospectively by participants 
indicating the number of cigarettes smoked each day (Sobell and Sobell, 1992). The TLFB yields 
consistently high test-retest correlations and correlates well with other self-reports and collateral 
reports. Use of other drugs of abuse, including prescription drugs, will also be assessed using the 
TLFB.   
 
 
6.3   
EXPLORATORY OUTCOMES 
Exploratory outcomes will include changes in characteristics related to cigarette use including craving for 
cigarettes (QSU, SASE, WSWS, FTND) and related areas of psychiatric functioning. 
• 
Fagerstrom Test of Nicotine Dependence (FTND): a 6-item questionnaire used to measure the 
level of dependence of cigarette smokers (Fagerström et al., 2012).  
• 
Questionnaire on Smoking Urges (QSU) is a multidimensional assessment of smoking craving 
with demonstrated sensitivity to smoking cessation (Tiffany & Drobes, 1991). It will be assessed 
at baseline, during interventional visits, and at each follow-up visit. 
• 
Wisconsin Smoking Withdrawal Scale 2 (WSWS2): measures severity of smoking withdrawal 
and exhibits good validity and reliability in smoking cessation studies (Shiffman et al., 2004; 
Welsch et al., 1999; Smith et al., 2021). It will be assessed at baseline, during interventional 
visits, and at each follow-up visit. 
• 
Generalized Anxiety Disorder Screener (GAD-7) (Spitzer et al., 2006)): The GAD-7 is a 7-item 
self-report instrument that will assess generalized anxiety symptomology. It will be assessed at 
baseline, during interventional visits, and at each follow-up visit. 
• 
Insomnia Severity Index (ISI): found to be a reliable and valid tool to quantify perceived insomnia 
severity and can be useful as an outcome measure in research studies (Bastien, 2001).  
• 
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 


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sacredness)  (Barrett et al., 2015; Maclean et al., 2012). It will be assessed at baseline, during 
interventional visits, and at each follow-up visit. 
• 
Five Facets of Mindfulness Questionnaire (FFMQ) (Baer et al., 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. It will be assessed at baseline, during interventional visits, and at each follow-
up visit. 
• 
Rhode Island Change Assessment (URICA) (Stephens et al., 2004): The URICA is a 
questionnaire designed to measure stage of change in psychotherapy with four scale 
scores derived corresponding to the precontemplation, contemplation, action and 
maintenance stages. It will be assessed at baseline, during interventional visits, and at 
each follow-up visit. 
• 
Beck Depression Inventory (BDI-II; Beck, Steer, & Brown, 1996). A widely used 21-item self-
report measure of depressive symptoms. 
   
 
7.0 
CONSENT PROCESS 
7.1 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.   
 
7.2 Location of Informed Consent 
Informed consent will be obtained at the study research offices, in a private and interruption-free 
environment. 
 
7.3 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. 
 
7.4 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.   
 
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. 


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8.2 Data Confidentiality Procedures 
We will take rigorous precautions to maintain confidentiality for all participants, using procedures that the 
PI and her 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, her mentors, and approved study personnel.  All data will be 
confidentially stored (i.e., in locked files or on encrypted servers) 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 in compliance with MUSC 
regulations. 
 
8.3 Data Quality Control Procedures 
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. Amador) 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 


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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 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 
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) 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 her 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. 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 be 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. Serious 
adverse effects (SAE) 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 to detect any worsening symptoms.  Additionally, participants will be 
advised to observe any signs of worsening substance use or psychiatric 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. Amador 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 


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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 anxiety severity. 
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.   
 
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 


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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 
post-dose by trained healthcare professionals (e.g. 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.  
 
Other rare risks of ketamine include cystitis which are likely due to repeated use of ketamine. There is 
also a small risk of anaphylaxis. 
 
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. 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.   
 


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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.  
 
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 tobacco use.  Participants may 
also gain diagnostic information about their medical or psychiatric comorbidities, 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 tobacco use disorder 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 165744 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 
 
Babb, S., Malarcher, A., Schauer, G., Ashman, K., Jamal, A. (2017). Quitting Smoking Amoung Adults – 
United States, 2000-2015. MMWR Morb Mortal Wkly Rep, 66, 1457-1464. 
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Baer, R. A., Smith, G. T., Hopkins, J., Krietemeyer, J., & Toney, L. (2006). Using self-report assessment 


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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 
Bastien, C. H., Vallières, A., & Morin, C. M. (2001). Validation of the Insomnia Severity Index as an 
outcome measure for insomnia research. Sleep medicine, 2(4), 297-307. 
Benowitz, N. L., Bernert, J. T., Foulds, J., Hecht, S. S., Jacob, P., Jarvis, M. J., Joseph, A., Oncken, C., 
& Piper, M. E. (2020). Biochemical Verification of Tobacco Use and Abstinence: 2019 
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Bruijnzeel, A. W., Alexander, J. C., Perez, P. D., Bauzo-Rodriguez, R., Hall, G., Klausner, R., ... & Febo, 
M. (2015). Acute nicotine administration increases BOLD fMRI signal in brain regions involved in 
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Cahill, K., Stead, LF., Lancaster, T. (2012). Nicotine receptor partial agonists for smoking cessation. 
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ttps%3A%2F%2Fwww.cdc.gov%2Ftobacco%2Fdata_statistics%2Ffact_sheets%2Findex.htm 
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antidepressant effects of intramuscular versus intravenous ketamine. Indian Journal of 
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Dakwar, E, Hart, C. L., Levin, F. R., Nunes, E. V, & Foltin, R. W. (2017). Cocaine self-administration 
disrupted by the N-methyl-D-aspartate receptor  antagonist ketamine: a randomized, crossover 
trial. Molecular Psychiatry, 22(1), 76–81. https://doi.org/10.1038/mp.2016.39 
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Dependence as a predictor of smoking abstinence: a pooled analysis of varenicline clinical trial 


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oral ketamine. British Journal of Anaesthesia, 53(8), 805–810. https://doi.org/10.1093/bja/53.8.805 
Hartmann-Boyce, J., Livingstone-Banks, J., Ordóñez-Mena, J. M., Fanshawe, T. R., Lindson, N., 
Freeman, S. C., Sutton, A. J., Theodoulou, A., & Aveyard, P. (2021). Behavioural interventions for 
smoking cessation: an overview and network meta-analysis. The Cochrane database of systematic 
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Jones, J. L., Mateus, C. F., Malcolm, R. J., Brady, K. T., & Back, S. E. (2018). Efficacy of Ketamine in 
the Treatment of Substance Use Disorders: A Systematic  Review. Frontiers in Psychiatry, 9, 277. 
https://doi.org/10.3389/fpsyt.2018.00277 
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Krupitsky, E., Burakov, A., Romanova, T., Dunaevsky, I., Strassman, R., & Grinenko, A. (2002). 
Ketamine psychotherapy for heroin addiction: immediate effects and two-year  follow-up. Journal 
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Krupitsky, Evgeny M, Burakov, A. M., Dunaevsky, I. V, Romanova, T. N., Slavina, T. Y., & Grinenko, A. 
Y. (2007). Single versus repeated sessions of ketamine-assisted psychotherapy for people with  
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Cochrane database of systematic reviews, 3(3), CD001292. 
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Xu, Y., Hackett, M., Carter, G., Loo, C., Gálvez, V., Glozier, N., … Rodgers, A. (2016). Effects of Low-
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https://doi.org/10.1093/ijnp/pyv124 
 
 
 
 
 
 
 
 
 
 
 
 

ICF_000.pdf: 
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IRB Number: «ID» 
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Medical University of South Carolina 
CONSENT TO BE A RESEARCH SUBJECT 
 
TITLE OF RESEARCH:  Ketamine-assisted Motivational Enhancement Therapy for the Treatment of 
Tobacco Use Disorder 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 is able to improve treatment 
outcomes for smoking cessation. If you are eligible and you decide to participate in the study, your 
participation will last approximately 12 weeks, or 3 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 3 clinic visits (once per week, lasting 2-3 hours per visit). At 
each of these visits, you will be asked to answer several questionnaires and provide a saliva sample 
to test for recent nicotine use and a urine sample to check for pregnancy in persons of child-bearing 
potential. At the initial visit, you will be asked to provide a urine sample for a drug screen. You will 
meet with a study coordinator to discuss motivations and goals for smoking cessation. 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. A clinician will be available during and after 
treatment to discuss your experience. At the clinic visits where the study medication is administered, 
you will not be allowed to drive home. You will also meet with our study physician 4 and 8 weeks after 
your final medication session. These follow-ups (lasting half hour to an hour) will include 
questionnaires and saliva nicotine testing and 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 of childbearing potential, 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 having a lower desire to smoke cigarettes or feeling 
like it is easier to remain abstinent from cigarettes, however, personal benefits cannot be guaranteed.  
Your alternative is not to participate in the study. Alternative treatments are available for individuals 
with tobacco use disorder including medications such as varenicline, bupropion, and nicotine 
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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 tobacco use disorder, specifically to decrease cigarette use. 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 tobacco use disorder.  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 tobacco 
use disorder.  You are being asked to participate because you are over 21 years of age and you 
currently have tobacco use disorder. Approximately 8 people will take part in this study. 
 
The investigator in charge of the study is Dr. Emily Amador at the Medical University of South 
Carolina (MUSC).  This study is being conducted with funding from a grant from the National Institute 
on Drug Abuse (NIDA) through the Diversity in Addiction Research Training program. 
 
 
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 other substances, such as 
alcohol, level of cigarette use, craving levels for nicotine, motivation to quit smoking, 
and other symptoms such as anxiety and insomnia. 
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 and includes blood 
pressure, pulse, and temperature measurements. 
o We will complete a baseline 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 365 days 
at MUSC, your medical record will be reviewed. If this test was normal, you may not 
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o A saliva sample will be collected at baseline and follow-up to determine recent nicotine 
use. 
o A urine sample to test for recent use of recreational psychoactive drugs 
o A urine pregnancy test (only if you are an individual of childbearing potential). The 
urine pregnancy test must be negative to participate. 
 
• 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 3 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 an individual of childbearing potential, 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 3 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 saliva 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 an 
individual of childbearing potential). The urine pregnancy test must be negative to participate. 
• You will also be weighed prior to administration of the investigational medication to ensure 
accurate dosing. 
• Each medication visit will include motivational-based psychotherapy, which is a type of 
counseling that focuses on motivation and setting goals. Examples of this therapy 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 investigational 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 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. 


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• The investigational medication, ketamine, is given by intramuscular injection. After receiving 
the injection, you will be instructed to rest in a chair. After approximately 60-90 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. 
Reimbursement will be a flat rate of $100 to cover compensation for time and travel for each 
visit. 
 
3. Follow-Up Visits (approximately 30 to 60 minutes each in length): 
• Completion of written questionnaires related to your mental and physical health. 
Questionnaires will also be related to recent use of tobacco products, your cravings and 
withdrawal symptoms related to nicotine and motivation to quit smoking as well as 
symptoms of anxiety and insomnia. At these visits, you will complete saliva testing for 
recent nicotine use. 
• 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 6 visits over a period of approximately 3 months.  There will be 
an initial screening visit (approximately 2-3 hours), 3 study medication visits (approximately 2-3 hours 
each), and 2 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.   
 
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)  


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• 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 (greater than 180 mmHg systolic blood 
pressure or greater than 105 mmHg diastolic blood pressure, or greater than 30 mmHg in systolic or diastolic 
blood pressure above baseline values), you will be treated with a blood pressure medication 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), sedation (10 
percent), slow heart rate (4%), and low blood pressure. Syncope (or passing out) is a rare but 
possible side effect of clonidine. 
 
Ondansetron Risks: 
If you experience clinically significant nausea which is causing discomfort and/or vomiting, you will be 
treated with an antiemetic medication called ondansetron. The most common side effects of 
ondansetron include constipation (10 percent) and headache. 
 


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Alprazolam Risks: 
If you experience clinically significant anxiety which is causing psychiatric distress or discomfort such 
as tense muscles, hyperventilation, or trembling, you will be treated with an anxiolytic medication 
called alprazolam. The most common side effects of alprazolam include drowsiness, decreased 
alertness, confusion, ataxia, memory impairment, and hypotension. 
 
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.  
 
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 as a result 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. 
 
Unknown Risks: The experimental treatments may have unknown side effects. The researchers will let 
you know if they learn anything during the course of the study that might make you change your mind 
about participating in the study.  
 
E. MEDICAL RECORDS AND/OR CERTIFICATE OF CONFIDENTIALITY 
 
Information about your study participation will not be in your medical record.  This means that neither 
your research participation nor any of your research results will be included in any MUSC medical 
record. This means that your research participation, saliva 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 standard 
treatments for smoking cessation, you may benefit from participating in the study.  However, given the 


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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 tobacco use 
disorder. 
 
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.  
 
 H. PAYMENT TO PARTICIPANTS 
 
Initial evaluation, three weekly medication sessions, and 2 follow up visits will not result in 
compensation other than reimbursement for time and local travel expenses. Reimbursement will be a 
flat rate of $100 to cover compensation for time and travel for each in-person clinic visit. Payment for 
local travel expenses will be made using a prepaid 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 tobacco use disorder include both medications (such as varenicline, bupropion, 
and nicotine replacement therapy) and counseling-based treatments (including group sessions such as 
individual or group counseling sessions).  
Withdrawal from the Study 
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 participants 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 
choose not to sign, it will not affect your treatment, payment or enrollment in any health plan or affect 


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IRB Number: «ID» 
Date Approved «ApprovalDate» 
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 course of 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. CLINICAL TRIALS.GOV  
 


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IRB Number: «ID» 
Date Approved «ApprovalDate» 
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 
 
Saliva specimens will be collected in this study. All participants will provide a saliva sample during the 
screening phase and at each subsequent visit. Urine samples will be collected from individuals of 
childbearing potential to be checked for pregnancy at the baseline visit and every medication visit. 
Results of saliva and urine testing (pregnancy) 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 appropriately discarded with out 
identifying markers. 
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:  
____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 for virtual follow-up visits.  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 
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 


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IRB Number: «ID» 
Date Approved «ApprovalDate» 
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 (Dr. Emily Amador) at (843) 608-
1216 or via e-mail at amador@musc.edu.  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 for paper consents or scroll to the bottom of the screen to provide an electronic signature. 
 
 
________________________________________     
Signature of Participant                                Date   
 
 
  
________________________________________     
Printed Name of Participant                          Date   
 
________________________________________     
 
Signature of Person Obtaining Consent       Date