Clinical trial NCT02422290
Conditions: Obsessive-Compulsive Disorder
Keywords: Obsessive Compulsive Disorder Ketamine Glutamate OCD treatment OCD medication
Sponsor: New York State Psychiatric Institute
Start date: 2015-03-01; Completion date: 2020-07-31
Enrollment: 5 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This pilot study is proposed to determine the acceptability, feasibility and potential efficacy of ketamine, a medication that modulates glutamate in the brain, as a rapid treatment for obsessive-compulsive disorder (OCD) symptoms in adolescents and young adults with OCD. This study will recruit 6 youth (ages 14-22) who are diagnosed with clinically significant OCD and have failed at least one adequate trial of a Serotonin Reuptake Inhibitor (SRI) medication and a course of Cognitive-Behavioral Therapy (CBT) (unless unable to access or tolerate) for OCD in the past. Participants will receive a single infusion of intravenous ketamine and be assessed at regular intervals post-infusion for up to 14 days. At the end of the 14-day treatment phase, all participants will be offered three months of open treatment for OCD with medication and/or CBT.

Detailed description:
See Brief Summary for description.

Arms: arm 1: All participants will be receive the intravenous ketamine infusion.
Interventions: intervention 1: Ketamine
Intervention descriptions: intervention 1: Single infusion of IV Ketamine, 0.5mg/kg

Protocol documents:
Prot_000.pdf: 
Protocol Summary Form
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Goldberg, Pablo
Page 1 of 30
Protocol Title:
Ketamine Treatment for Pediatric-
Refractory Obsessive-Compulsive Disorder 
(OCD)
Protocol Number:
7023
First Approval:
02/13/2015
Expiration Date:
01/25/2019
Version Date:
01/17/2018
Clinic:
Children's Day Unit
Contact Principal Investigator:
Pablo Goldberg, MD
Email: GoldberP@nyspi.columbia.edu
Telephone: 646-774-6318
Co-Investigator(s):
Helen Simpson, MD
Moira Rynn, MD
Cover Sheet
Choose ONE option from the following that is applicable to your study
If you are creating a new protocol, select "I am submitting a new protocol." As 5 Year Renewals are no 
longer required, this option remains for historical purposes.
I am submitting an annual continuation without modifications 
Division & Personnel
Division
What Division/Department does the PI belong to?
Child Psychiatry
Within the division/department, what Center or group are you affiliated with, if any? 
Pediatric Anxiety and Mood Research Clinic (PAMRC) / Children's Day Unit (CDU)
Unaffiliated Personnel
List investigators, if any, who will be participating in this protocol but are not affiliated with New York 
State Psychiatric Institute or Columbia University. Provide: Full Name, Degrees and Affiliation.
Evelyn Berger-Jenkins, MD, MPH (Assistant Professor of Pediatrics, Columbia University Medical Center)


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Moira Rynn, MD (Consulting Professor and Chair, Department of Psychiatry and Behavioral Sciences, 
Duke University Medical Center) 
Application for Continuation of Research
Status
Current Status of Study: 
Subject enrollment is ongoing.
Summary of Experiences to Date
Please provide a summary of scientific progress of the study and the experience of research participants, to 
date. This requirement is designed to allow for the investigator and the IRB to reassess the study’s risks and 
benefits in terms of developments in the field, changing practice patterns, and new IRB policies and 
procedures.
We have enrolled 5 participants to date. We have not had any serious events related to
the ketamine infusion. The participants and their families have reported satisfaction with their participation 
in the study. We have provided case reports to the IRB highlighting participants' experience.
Funding
Have there been any changes in funding status since the prior approval? 
No
Have the principal investigator and other investigators made all required disclosures of financial interest in 
the study sponsor/product?
Yes
Summary
Have there been any study findings, recent literature, or untoward events occuring here or at other sites in 
the past year which might affect the analysis of the safety, risks or benefits of study participation? 
No
Have there been any serious adverse events (serious and/or unanticipated problems involving risks to 
subjects or others at this site which occured in the past year)? 
No
Have all study staff with a significant role in the design or implementation of the human subject components 
of this study received required training in human research subject protections?
Yes
Is the study covered by a certificate of confidentiality? 
No


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Overall Progress
Approved sample size
10
Total number of participants enrolled to date
5
Number of participants who have completed the study to date 
4
Have there been any significant deviations from the anticipated study recruitment, retention or completion 
estimates? 
No
Comments / additional information 
Sample Demographics
Specify population
Adolescents and young adults with OCD
Total number of participants enrolled from this population to date 
5
Gender, Racial and Ethnic Breakdown 
We have screened a total of 9 participants and completed the study with 4 participants. 1 participant is 
currently in the 3-month follow-up period. 
 
Gender:
- Male:1
- Female: 4
 
Race/Ethnicity:
- White: 4
- Mixed race: 1  
Summary of Current Year's Enrollment and Drop-out 
Number of participants who signed consent in the past year
3
Number of participants currently enrolled
1
Did the investigator withdraw participants from the study? 
No
Did participants decide to discontinue study involvement? 
No


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Procedures
To create the protocol summary form, first indicate if this research will include any of the following 
procedures
   Psychiatric Assessment
   Collection of Biological Specimens
   Medication Trial
   Medication-Free Period or Treatment Washout
   Off-label Use of Drug or Device
Population
Indicate which of the following populations will be included in this research
   Children (ages 13-17)
   Adults
Research Support/Funding
Will an existing internal account be used to support the project?
Yes
Describe internal account
PC002246     YAC Columbia account
 
903-4081A    RFMH account
 
903-4132A   RFMH account 
 
Is the project externally funded or is external funding planned?
Yes
Select the number of external sources of funding that will be applicable to this study
Funding Source #1
Is the PI of the grant/contract the same as the PI of the IRB protocol? 
Yes
Select one of the following
The grant/contract is currently funded
Source of Funding
Other
Sponsor


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NYPH YAC (Youth Anxiety Center)
Select one of the following
Single Site
Business Office
CU
Does the grant/contract involve a subcontract? 
No
Study Location
Indicate if the research is/will be conducted at any of the following
   NYSPI
   Other Columbia University Medical Center Facilities
This protocol describes research conducted by the PI at other facilities/locations
No
Lay Summary of Proposed Research 
Lay Summary of Proposed Research
This pilot study is proposed to determine the acceptability, feasibility and potential efficacy of ketamine, a 
medication that modulates glutamate in the brain, as a rapid treatment for obsessive-compulsive disorder 
(OCD) symptoms in adolescents and young adults with OCD. This study will recruit 10 youth (ages 14-22) 
who are diagnosed with clinically significant OCD and have failed at least one adequate trial of a Serotonin 
Reuptake Inhibitor (SRI) medication and a course of Cognitive-Behavioral Therapy (CBT) for OCD in the 
past. Participants will receive a single infusion of intravenous ketamine and be assessed at regular intervals 
post-infusion for up to 14 days. At the end of the 14-day treatment phase, all participants will be offered 
three months of open treatment for OCD with medication and/or CBT. The study will be conducted at 
NYSPI and will follow similar methodology to the approved protocol that studied the effects of ketamine in 
adults with OCD (IRB#5833, PI: Dr. Carolyn Rodriguez, now being analyzed under IRB#7219, PI: Dr. 
Helen Blair Simpson). Promising data will lead to a grant application to the National Institutes of Mental 
Health for a full-scale randomized controlled trial. 
 
Background, Significance and Rationale
Background, Significance and Rationale
Overview:


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Obsessive-compulsive disorder (OCD) is a disabling illness that usually begins by adolescence, persists for 
life, and impairs function. There have been no new classes of Food and Drug Administration (FDA)-
approved medications to treat children and adolescents with OCD since the development of serotonin 
reuptake inhibitors (SRIs) over 30 years ago. SRIs provide only limited symptom relief and typically have a 
2-3 month lag time before clinically meaningful improvement. Thus, there is a compelling need for 
alternative pharmacological treatments in adolescents with OCD. At the same time, there has been a surge in 
our understanding of the pathophysiology of OCD: it is associated with abnormal functioning of a 
corticostriatal circuit, and there are known abnormalities within the glutamate neurotransmitter system (e.g. 
glutamate is the main excitatory chemical that helps nerve cells communicate). These basic science findings 
have recently prompted excitement in testing medications that target glutamate to decrease OCD symptoms.
Background & Rationale: 
In this study, we will evaluate the feasibility, tolerability, and preliminary efficacy of ketamine, a 
medication that modulates glutamate in the brain, as a rapid treatment for OCD symptoms in adolescents 
and young adults with OCD. Our rationale for using ketamine is threefold. First, glutamatergic 
abnormalities in corticostriatal circuits may underlie OCD symptoms based on human imaging, genetic, and 
animal studies; 1-3 striatal glutamatergic levels have been associated with OCD severity. 4, 5 Thus, 
medications that modulate glutamatergic neurotransmission (e.g., riluzole, memantine, minocycline) may be 
effective.5, 6 Second, riluzole and memantine have shown promise for OCD in case reports or open trials, 7-
9 but neither is FDA-approved for use in children; riluzole also has significant liabilities in terms of adverse 
events and cost. 10 In contrast, ketamine is FDA-approved for anesthesia and chronic pain in children, 
adolescents and adults, and is routinely used at higher doses than proposed in this study. 11 It is also used as 
adjunctive pain management for children and adolescents suffering from end stage medical illness.12-13 
Third, we found in a small randomized controlled trial that unmedicated OCD adults had a near cessation of 
obsessional thoughts during an intravenous ketamine infusion; these effects were maintained in half of the 
patients for up to one week.14 These exciting findings lead to two questions: 1) is this type of study 
acceptable and feasible in youth; 2) are ketamine’s effects similar in adolescents and young adults? This 
proof-of-concept study has the potential to pave the way to rapid-acting treatment strategies for adolescents 
and young adults with OCD. 
Our decision to allow participants to remain on their prescribed SRI medications during the study is based 
on a review of the literature. There are no known interactions between these medications. Additionally, 
three published psychiatric studies have allowed patients to concurrently take antidepressant medications 
and ketamine.15-17 These studies have a combined sample size of 92 participants, and there were no related 
adverse events.  Refer to the uploaded chart titled "SRI - Ketamine Literature Summary" for more 
information.
Specific Aims and Hypotheses
Specific Aims and Hypotheses
Specific Aims:


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The goal of this proof-of-concept study is to investigate the effect of ketamine on the symptoms of OCD in 
adolescents and young adults ages 14-22. The symptoms of OCD are evaluated using a number of validated 
scales designed to measure their clinical status. The specific aims of the study are as follows:
 
Aim 1. To assess the acceptability, feasibility and tolerability of a single ketamine infusion in adolescents 
and young adults with OCD.
Aim 2. To assess the effects of ketamine on OCD severity.
 
Primary Hypothesis:
Adolescent and young adult OCD patients will have a reduction in OCD symptoms immediately following 
the ketamine infusion.
Description of Subject Population
Sample #1
Specify subject population
Individuals with obsessive-compulsive disorder
Number of completers required to accomplish study aims
10
Projected number of subjects who will be enrolled to obtain required number of completers
20
Age range of subject population
14-22 inclusive
Gender, Racial and Ethnic Breakdown
Based on our experience and the demographics of the catchment area served by our institution, we expect 
the subject racial distribution to be approximately 73% White, 18% Black, 9% Asian, and for the ethnic 
distribution to be approximately 22% Hispanic. We expect the sample to be 50% female.
Description of subject population
We will recruit 10 adolescents and young adults (post-pubertal, ages 14-22) with OCD using similar criteria 
as in the prior study in adults 14 with the modification that participants have had at least one adequate trial 
of an SRI medication and a course of CBT for OCD. They will be free of medication or on a stable dose of 
an SRI medication, score ≥ 16 on the Children’s Yale-Brown Obsessive Compulsive Scale (CYBOCS) prior 
to entering the study and report at least moderate severity of obsessions and/or compulsions.
Recruitment Procedures
Describe settings where recruitment will occur
The study will recruit participants from the Anxiety Disorders Clinic (ADC), directed by Dr. Simpson, as 


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well as the CAPES Evaluation Service and the Children’s Day Unit (CDU), which are directed by Dr. Laura 
Mufson. The ADC screens over 200 adults (≥ 18) with OCD a year. The CAPES/CDU provides free expert 
consultation, evaluation, and treatment referrals for children and adolescents suffering from mood and 
anxiety disorders. OCD self-help organizations such as the International OCD Foundation will be contacted 
to further publicize the existence of this study.
Participants (ages 14-22) and their parent/caregiver will be assessed by an IRB-approved phone screen 
(IRB# 7058R (formally 6019R), IRB# 6574). For participants ages 18-22, the research team will obtain 
permission from the participant before speaking to his/her parent/caregiver. We do not communicate to 
families that we will destroy their screening information if they do not come in for a study visit. Regardless 
of study participation, we enter the information from the phone screens into a deindentifed and password 
protected database.
 
How and by whom will subjects be approached and/or recruited? 
Research staff on the CDU and ADC may approach and discuss the research study with potential 
participants who have given permission to be contacted about research. Drs. Goldberg and Simpson will be 
responsible for fully explaining the details of the study, answering any questions, and consenting the 
participants if they are interested in the study. 
 
How will the study be advertised/publicized? 
IRB-approved radio/newspaper/web advertisements, flyers and RecruitMe will be used to recruit 
participants.
 
Do you have ads/recruitment material requiring review at this time? 
No
Does this study involve a clinical trial?
Yes
Please provide the NCT Registration Number
NCT02422290
Concurrent Research Studies
Will subjects in this study participate in or be recruited from other studies? 
Yes
Describe concurrent research involvement
Participants may be recruited from the following ongoing studies:
“Evaluation at the NYSPI Child Psychiatry Research Clinic.” (IRB# 7058R)
“MRS Glutamate Measurement in Healthy Controls and People with OCD." (IRB #6218)
"Novel Medication Strategies Targeting Brain Mechanisms in Pediatric OCD." (IRB #6574)


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"Attaining and Maintaining Wellness in OCD." (IRB #6628)
 
Inclusion/Exclusion Criteria
Name the subject group/sub sample
OCD Participants
Create or insert table to describe the inclusion criteria and methods to ascertain them
CRITERION
METHOD OF ASCERTAINMENT
1) Participant must be 14-22 years of age at the time 
of consent (post-pubertal)
Phone screen, inquiry at time of consent 
by trained research staff 
2) Participant and a parent/guardian must be able to 
read and understand English
Phone screen, inquiry at time of consent 
by trained research staff 
3) Participant must be physically healthy and weigh 
at least 25kg. If female, must not be pregnant.
Clinical interview by trained MD or PhD, 
physical examination, EKG, and blood 
tests
4) Participant must fulfill DSM-V criteria for OCD, 
OCD being the principal disorder (i.e., currently the 
most severe and in need of treatment) and have had 
OCD for at least six months. 
Clinical interview and results of ADIS-
C/P
5) Participant must score ≥ 16 on the Children’s 
Yale-Brown Obsessive Compulsive Scale 
(CYBOCS) prior to entering the study, report at 
least moderate severity of obsessions and/or 
compulsions..
CYBOCS administration by trained rater, 
OCD-VAS
6) Participant must have tried and failed at least one 
adequate trial of an SSRI medication or 
clomipramine and a course of CBT unless the 
participant is unable (or unwilling) to access or 
tolerate CBT treatment.
 
a.  In order to meet criteria for having had at least 
one adequate trial of an SRI medication, 
participants must have been on a stable and minimal 
adequate dose of at least one SSRI medication or 
clomipramine as defined by the literature for at least 
12 weeks, and have a documented history of 
intolerable adverse effects at a higher dose as 
evaluated by the study psychiatrist and are therefore 
unable to increase the dose or complete the full 12 
Phone screen, clinical interview, 
consultation with referring physician


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Create 
or insert 
table to 
describe 
the 
exclusio
n 
criteria 
and 
methods 
to 
ascertain 
them
weeks, or have refused further SRI trials. Congruent 
with the literature, the range of minimally adequate 
doses to treat OCD are as follows: Clomipramine 
(Anafranil) 75-100 mg/day; Fluoxetine (Prozac) 20-
60 mg/day; Paroxetine or Paroxetine CR (Paxil) 20-
40 mg/day; Sertraline (Zoloft) 50-100 mg/day; 
Fluvoxamine (Luvox) 100-200 mg/day; Citalopram 
(Celexa) 20-40 mg; Escitalopram (Lexapro) 10-20 
mg/day for a minimum of 12 weeks. 
 
b.  In order to meet criteria for having had an 
adequate course of CBT for OCD, patients should 
have received at least 8 sessions of Exposure and 
Response Prevention Therapy (EX/RP) by a 
licensed clinician trained in doing CBT for OCD. A 
CBT expert on our team will ensure that the 
clinician administering these exposures has had 
adequate training and experience in providing this 
treatment. Participants may also be considered if 
they are unable to access or unwilling to pursue 
CBT treatment.
7) Participant is off all psychotropic and other types 
of drugs likely to interact with glutamate for at least 
14 days before starting the study. The exceptions 
are SRI medications and short acting 
benzodiazepines for distressing anxiety or insomnia 
(which can be taken up to 24 hours prior to 
ketamine infusion). Participants will be off 
neuroleptics for 1 month and off fluoxetine for 6 
weeks prior to the study. 
Phone screen, clinical interview, 
consultation with referring physician
8) For participants younger than 18, written 
informed assent by the participant and consent by 
the parent. For participants 18 and older, written 
consent by the participant and permission for legal 
guardian/parent to provide information.
Consent interview by study psychiatrist


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CRITERION 
METHOD OF ASCERTAINMENT
1) Family history of a first degree relative with psychosis 
or substance abuse/dependence.
Clinical interview
2) History of violence
Clinical interview
3) Presence of psychotic symptoms or lifetime diagnosis 
of schizophrenia including any auditory or visual 
hallucinations or presence of delusional thinking, bipolar 
disorder, substance-induced psychotic disorder, psychosis 
due to general medical condition. 
Clinical interview, ADIS-C/P
4) Severely depressed patients with the Children’s 
Depression Rating Scale (CDRS) ≥ 60 or judged 
clinically to be at risk of suicide.
Clinical interview, ADIS-C/P and CDRS
5) Current diagnosis of an eating disorder.
Clinical interview, ADIS-C/P
6) Current or past history of PTSD or significant trauma.
Clinical interview, ADIS-C/P
7) Current or past diagnosis of substance 
abuse/dependence. 
Clinical interview, ADIS-C/P
8) Current or past diagnosis of autism or a related 
disorder.
Clinical interview
9) Current or past diagnosis of pediatric autoimmune 
neuropsychiatric disorders associated with streptococcus 
(PANDAS). This will be defined by the following 
criteria: abrupt onset of OCD symptoms (often with 
comorbid tics) with a relapsing–remitting symptom 
course, a temporal association between symptom 
exacerbations and a Group-A beta-hemolytic 
streptococcal (GAS) infection, association with 
neurological abnormalities during exacerbations 
(adventitious movements, motoric hyperactivity, urinary 
hesitancy), and prepubertal age of onset.
Clinical interview
10) Participants planning to commence cognitive-
behavioral therapy during the period of the study or those 
who have begun CBT within 8 weeks prior to enrollment.
Phone screen, clinical interview, consultation 
with current provider
11) Documented history of hypersensitivity or intolerance 
to ketamine.
Clinical interview
12) Female participants who are either pregnant or 
nursing or female participants of child bearing age who 
are sexually active and not taking hormonal birth control.
Medication evaluation 
13) History of significant medical condition that might 
increase the risk of participation. This would include 
hypertension (BP > 140/90), chronic congestive heart 
failure, tachyarrhythmias, myocardial ischemia, 
intracranial mass lesions, head injury, globe injuries, 
hydrocephalus or a thyroid disorder.
Clinical interview and medical examination
14) Concurrent use of any medications that might increase Clinical interview


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Waiver of Consent/Authorization
Indicate if you are requesting any of the following consent waivers
Waiver of consent for use of records that include protected health information (a HIPAA waiver of 
Authorization) 
No
Waiver or alteration of consent
Yes
Waiver of documentation of consent 
No
Waiver of parental consent 
No
Consent Procedures
Is eligibility screening for this study conducted under a different IRB protocol?
No
Describe procedures used to obtain consent during the screening process 
Prior to initiating screening procedures, Drs. Goldberg or Simpson will obtain consent from the participant 
(if 18 or older) or participant's parent/legal guardian by describing the purpose and nature of this research 
study. Families will have a chance to review the consent form thoroughly and ask any questions prior to 
signing.
Describe Study Consent Procedures
Drs. Goldberg or Simpson will answer any questions the participant or participant's parent/legal guardian 
may have and will obtain written consent. The participant/participant's parent/legal guardian will receive a 
copy of the signed consent.
Indicate which of the following are employed as a part of screening or main study consent procedures
   Consent Form
the risk of participation. This would include: St. John’s 
Wort, Tramadol, atracurium or thyroid medication, due to 
potential adverse drug-drug interactions.
15) Positive urine screen for illicit drugs
Urine toxicology assessment
16) Inability of participant or parent/guardian to read or 
understand English.
Phone screen, inquiry at time of consent by 
trained research staff. 
17) Documented history of adverse reaction to anesthesia.
Clinical interview 


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Justification for Waiver or Alteration of Consent
Waiver of consent is requested for the following
The waiver was requested to allow us to obtain information on participants’ family history. The Family 
history screen (FHS) form was previously uploaded for IRB review. As per Federal Regulation 45CFR46. 
116(d), (1) The research involves no more than minimal risk to the subjects; (2) The waiver or alteration 
will not adversely affect the rights and welfare of the subjects; (3) The research could not practicably be 
carried out without the waiver or alteration; and (4) Whenever appropriate, the subjects will be provided 
with additional pertinent information after participation.
 
Explain why your research can not be practicably carried out without the waiver or alteration
The FHS is a standardized questionnaire that will be used to screen for the presence of 15 psychiatric 
disorders among the participant’s biological relatives and patients with a family history of psychosis or 
substance use/dependence will be excluded from participating in this study. It would not be feasible to 
contact all of the patient's biological relatives to complete this form. Consent will be obtained from the 
parents of patients under 18 years to be able to collect this information via the FHS form.  
Describe whether and how subjects will be provided with additional pertinent information after participation
The participants and their families will be not be provided with any additional information after 
participation in the study.  
Assent Procedures
Describe procedures by which subject assent will be assessed and/or recorded
Drs. Goldberg or Simpson will describe the purpose and nature of the research study. The participant will 
have a chance to review the assent form thoroughly and ask any questions prior to signing. If they decide to 
participate in the study, they will also receive a copy of the signed assent form.
Persons designated to discuss and document consent
Select the names of persons designated to obtain consent/assent
Goldberg, Pablo, MD
Simpson, Helen, MD
Type in the name(s) not found in the above list
Study Procedures
Describe the procedures required for this study
Overview: 


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The current plan is for the study to be conducted at the Children’s Day Unit (CDU) at NYPSI and the Irving 
Institute for Clinical and Translational Research at CUMC. The CDU is an outpatient clinic and a research 
day treatment program that provides services for the psychiatric and educational needs of children and 
adolescents participating in research protocols at NYSPI. Most of the children have either failed or not 
completely responded to first line treatments for mood, OCD, or other anxiety disorders. School services are 
provided by PS186X, a New York City public school located on the unit during the academic year from 
September through June. In addition, during the 6 week summer program in July and August, the CDU 
provides educational tutoring. This unit provides continued clinical care for children and adolescents after 
their participation in an IRB approved protocol at no cost. Led by Dr. Mufson, the staff consists of a 
research medical director, Dr. Pablo Goldberg, a research nurse, a social worker, psychologists, and 
trainees. Although this protocol is primarily conducted as an outpatient study, we reserve the opportunity to 
offer admission to 4 Center (the 4th floor inpatient unit) for those adolescents in need of a higher level of 
care. If an adolescent requires additional support, the adolescent may be admitted to the CDU partial day 
program that runs Monday through Friday from 8:30 AM to 3:30 PM where the adolescent can be closely 
monitored, receive educational credit, and additional supportive services. 
Screening:
Upon consenting, participants will complete all screening procedures at the CDU. Screening may last from 
1 to 6 weeks to allow sufficient time to obtain thorough medical and psychiatric history to ensure the 
patient’s safety and eligibility/ineligibility in the study. Screening procedures include:
         Diagnostic Assessment: Anxiety Disorders Interview Schedule - Child/Parent version (The child 
version will be administered to all participants. The parent version will be administered to parents of 
all participants ages 14-17 and to parents of participants ages 18-22 with their permission). 
         Efficacy Assessments: Children’s Yale-Brown Obsessive Compulsive Scale (CYBOCS), Children’s 
Depression Rating Scale-Revised (CDRS-R).
Note: Diagnostic and Efficacy Assessments will be be administered by one of the study's Independent 
Evaluators (Dr. Paula Yanes-Lukin, Dr. Chiaying Wei, Juliet Jenkelowitz or Kristin Toffey).
         Feasibility and Safety Assessment: Columbia-Suicide Severity Rating Scale (C-SSRS)
         Clinical Global Impressions Scale (CGI), Medical History, Treatment History, Family History, 
OCD Onset form.
         Medical Assessment: Physical examination, EKG, Tanner Scale, Safety Labs, Vital Signs and 
Pregnancy Test (serum)
If clinically indicated, study clinicians may administer the Social Communication Questionnaire 
(SCQ) and/or an OCPD assessment based on DSM criteria (uploaded). 
Note: If the subject has been screened under IRB protocol #6019R “Evaluation at the NYSPI Child 
Psychiatry Research Clinic” or IRB protocol #6574 “Novel Medication Strategies Targeting Brain 
Mechanisms in Pediatric OCD” within 1 month of screening for this study, and do not have any new 


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medical or psychiatric diagnoses that would prevent study entry, they do not need a repeat ADIS or intake in 
order to reduce patient burden and promote data sharing.
Co-Morbid Depression: Patients with co-morbid depression will be allowed in the study as long as OCD is 
primary, the Children’s Depression Rating Scale-Revised (CDRS-R) is <60, and patient is not currently 
suicidal. We would like to include patients with co-morbid MDD since ketamine has been shown to have 
rapid anti-depressant effects 15, 16; thus, assessing the response of these patients to ketamine would allow us 
to understand the impact of co-morbid MDD on OCD symptoms (in addition to our main goal of 
understanding ketamine’s effects on OCD patients without co-morbidities).
Washout:
In order to be eligible for this study, participants must be off all psychotropic medications aside from SRIs 
and other types of drugs likely to interact with glutamate for at least 14 days prior to starting the study. After 
consent is signed, if a medication washout is necessary, it can either be performed by a psychiatrist at the 
Pediatric Anxiety & Mood Research Clinic (PAMRC) or by the participant’s own physician. During this 
washout period, patients will be monitored at least weekly in person and by phone more frequently if 
needed. Weekly assessments during the washout period will include the Clinical Global Impressions Scale 
(CGI-S). If a patient’s score on the Global Improvement section of the CGI is a 6 (“much worse”) or 7 
(“very much worse”) during the washout period, the clinician will take the patient off the protocol washout 
and initiate the 3-month open clinical treatment offered to all patients at the end of the study. Patients may 
independently elect to withdraw from standardized treatment at any time for any reason, independent of 
their CGI Global Improvement score. Physical exam, vital signs and adverse events will also be carefully 
assessed during the washout period. 
Day 1: Baseline Evaluation & Ketamine Infusion
Baseline Evaluation
After completing the screening procedures and medication washout if applicable, participants will proceed 
to the baseline evaluation. Baseline evaluation procedures include:
         Efficacy Assessments: Children’s Yale-Brown Obsessive Compulsive Scale (CYBOCS), Children’s 
Depression Rating Scale-Revised (CDRS-R), Young Mania Rating Scale (YMRS), Clinician 
Administered Dissociative States Scale (CADSS), Brief Psychiatric Rating Scale (BPRS), OCD 
Visual Analogue Scale (OCD-VAS), Yale-Brown Obsessive Compulsive Challenge Scale 
(YBOCCS), Child Obsessive-Compulsive Impact Scale-Revised (COIS-R)
         Feasibility and Safety Assessment: Columbia-Suicide Severity Rating Scale (C-SSRS)
         Clinical Global Impressions Scale (CGI)
         Medical Assessment: Vital Signs and Pregnancy Test (urine) for female participants
Test Day Procedures


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It is planned that the ketamine infusion take place on an inpatient unit at the Irving Institute for Clinical & 
Translation Research at CUMC. After completing the baseline evaluation, if a participant is eligible for the 
study, they will be escorted to the Irving Institute by PAMRC staff. For the infusion, the participant’s 
treatment team will comprise of a nurse, a Pediatric Advanced Life Support (PALS) certified pediatrician 
Dr. Evelyn Berger-Jenkins and the study MD (Dr. Pablo Goldberg). At the site of the infusion, a nurse will 
repeat the participant’s vital signs, place the IV, and set up the IV infusion pump. The ketamine infusion can 
begin as soon as PALS-certified pediatrician is present. After the infusion, the study MD and PALS certified 
pediatrician will remain present to monitor the participant throughout the 2-hour post-infusion observation 
period. 
Ketamine Infusion
Each participant will receive one slow intravenous infusion of 0.5mg/kg ketamine hydrocholoride. The 
infusion will be given over a course of 40 minutes. The study PI will meet with the research pharmacist and 
technician responsible for the preparation of infusions several days prior to the subject’s first test day. EKG 
will constantly be monitored prior to, during, and after the ketamine infusion. Blood pressure, heart rate and 
oxygen saturation will be monitored and recorded at 5-minute intervals at baseline and throughout the 
ketamine infusion. 
In addition to these medical assessments, after 20 minutes from the start of the infusion, the study MD will 
monitor participants closely using the Clinician Administered Dissociative States Scale (CADSS) and 
Clinical Global Impressions Scale (CGI). Participants will also be asked to complete the 1-item OCD Visual 
Analogue Scale (OCD-VAS) to monitor OCD symptoms over a rapid time frame. 
Safety and Termination of Ketamine Infusion
 
In case of nausea or anxiety, patients can be administered anti-nausea medications, such as Zofran 
0.15mg/kg/dose (a medication that helps to decrease nausea), or anxiolytics such as Ativan (a medication 
that helps to decrease nervousness) from the pharmacy formulary. In the case of excessive saliva 
production, Glycopyrrolate, 0.0025-0.005 mg/kg, (a medication that helps treat hypersalivation) can be 
administered. In the rare event of severe agitation, Haldol 0.1mg/kg/day in divided doses (an antipsychotic 
medication that helps decrease severe impulsive behaviors and uncontrolled movements), Ativan and 
Cogentin 0.02-0.05 mg/kg (a medication that helps with the side effects of Haldol) can be administered as 
well. The most common and severe adverse effects of these medication are described in the "Risks/ 
Discomforts/ Inconveniences" section of this protocol.
In case of very high blood pressure during the ketamine infusion, the infusion will be stopped; patients 
blood pressure will be monitored and if there is no decrease after 5 minutes, then either Clonidine, 0.05-
0.1mg x 1, or one dose of sublingual nitroglycerin, 0.4 mg, will be administered. If patients experience 
blurred vision, headache or chest pain as a result of high blood pressure or any other medical complications, 
urgent care will be provided. The ketamine infusion will be terminated if the patient complains of any 
uncomfortable symptoms of rising anxiety and agitation, or any other uncomfortable symptoms. The most 
common and severe adverse effects of nitroglycerin is described in the "Risks/ Discomforts/ 
Inconveniences" section of this protocol.
Post-Infusion


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Immediately after the infusion is complete, vital signs, EKG and responses on the Clinician Administered 
Dissociative States Scale (CADSS), Clinical Global Impressions Scale (CGI) and OCD Visual Analogue 
Scale (OCD-VAS) will be recorded by the study MD. 
Infusions will be started in the morning and patients will be observed for 2 hours after the infusion 
(ketamine has a half-life of 10-15 minutes; 2 hours is 8 half lives); the entire visit will last approximately 3 
hours. MD ratings will be administered at 60 minutes and 120 minutes post-infusion as per the attached 
study flowchart. 
At the conclusion of each test day (after the 2-hour observation period), the study MD will evaluate the 
patient to determine if the effects of the study drug infusion have resolved to the point that subjects are safe 
to return home. These evaluation criteria will consist of absence of significant deviations from baseline in 
vital signs, gait, mental status exam, and assessments listed in the study flowchart including BPRS and 
CADSS scales. In the case of an adverse psychiatric event, patients will be admitted either to the Pediatric 
Emergency Department at New York Presbyterian Hospital or directly to the fourth floor inpatient unit (4 
Center) at the New York State Psychiatric Institute, if clinically appropriate. The PALS-certified 
pediatrician will be available for the duration of the post-infusion 2-hour observation period. Once patients 
have been cleared by the MD to go home, adolescents will be required to leave the Irving Center with a 
parent or guardian and young adults will be required to leave the Irving Center with a parent or guardian or 
support person identified by the young adult.
Day 2 – 14: Post-Infusion Monitoring & Assessments
After the ketamine infusion, participants will be monitored closely for a 2-week period. The primary 
measure of change in OCD symptoms will be the Children’s Yale-Brown Obsessive Compulsive Scale 
(CYBOCS). This, along with additional measures will be administered during this 2-week period as follows:
          Days 2-6 post-infusion: OCD-VAS and YBOCCS are administered during optional daily phone 
calls (except when they have an in-person visit on day 3 or 4, during which these will be 
administered in person). 
The in-person visit between day 2-6 post infusion is not a required study visit and will be offered on a case-
by-case basis. During this period, if the study MD determines that an in-person visit is needed or if the 
participant requests an in-person appointment, they will be asked to come to the clinic and will complete the 
following assessments. Otherwise these assessments will be completed over the phone. 
          Day 3 or 4: Participants come to the CDU to complete the following assessments:
o   MD ratings: Columbia-Suicide Severity Rating Scale (C-SSRS), Young Mania Rating Scale 
(YMRS), Clinician Administered Dissociative States Scale (CADSS), Brief Psychiatric 
Rating Scale (BPRS), Clinical Global Impressions Scale (CGI).
o   Medical assessment: Vital Signs and Pregnancy Test (urine) for female participants
Note: If a patient’s score on the Global Improvement section of the CGI is a 6 (“much worse”) or 7 
(“very much worse”) compared to baseline at the day 3 or 4 study visit, the clinician will take the 


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patient off the protocol and initiate the 3-month open clinical treatment offered to all patients at the 
end of the study.
          Day 7 post-infusion: Participants complete the following assessments at the CDU or over the phone 
(if participants live far away):
o   IE ratings: Children’s Yale-Brown Obsessive Compulsive Scale (CYBOCS), Children’s 
Depression Rating Scale-Revised (CDRS-R), Clinical Global Impressions Scale (CGI).
o   MD ratings: Columbia-Suicide Severity Rating Scale (C-SSRS), Young Mania Rating Scale 
(YMRS), Clinician Administered Dissociative States Scale (CADSS), Brief Psychiatric 
Rating Scale (BPRS), Clinical Global Impressions Scale (CGI).
o   Self-report forms: OCD Visual Analogue Scale (OCD-VAS), Yale-Brown Obsessive 
Compulsive Challenge Scale (YBOCCS), Child Obsessive-Compulsive Impact Scale-
Revised (COIS-R).
o   Medical assessment: Vital Signs and Pregnancy Test (urine) for female participants
 Note: If a patient’s score on the Global Improvement section of the CGI is a 6 (“much worse”) or 7 
(“very much worse”) compared to baseline at the day 7 study visit, the clinician will take the patient 
off the protocol and initiate the 3-month open clinical treatment offered to all patients at the end of 
the study.
          Day 8-13 post infusion: OCD-VAS and YBOCCS are administered daily during optional phone 
calls.
          Day 14 post-infusion: Participants come to the CDU to complete the following assessments:
o   IE ratings: Children’s Yale-Brown Obsessive Compulsive Scale (CYBOCS), Children’s 
Depression Rating Scale-Revised (CDRS-R), Clinical Global Impressions Scale (CGI).
o   MD ratings: Columbia-Suicide Severity Rating Scale (C-SSRS), Young Mania Rating Scale 
(YMRS), Clinician Administered Dissociative States Scale (CADSS), Brief Psychiatric 
Rating Scale (BPRS), Clinical Global Impressions Scale (CGI).
o   Self-report forms: OCD Visual Analogue Scale (OCD-VAS), Yale-Brown Obsessive 
Compulsive Challenge Scale (YBOCCS), Child Obsessive-Compulsive Impact Scale-
Revised (COIS-R).
o   Medical assessments: Safety labs, vital signs, pregnancy test (urine) for female participants.
Follow-up Treatment
Upon completion of the 14-day study period, participants will be offered an additional 3 months of open 
treatment for OCD (medication management and/or CBT) as clinically indicated based on their treatment 


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history. If a participant has not yet had a trial of Clomipramine, we will offer that medication to the 
participant following the 14 day period. In the event that they prefer to be treated elsewhere, they will also 
be provided with referrals to community providers. With their permission, all participants will be assessed at 
a 3-month follow-up visit. Participants will be asked to return to the CDU to complete the following 
assessments: Children’s Yale-Brown Obsessive Compulsive Scale (CYBOCS), Clinical Global Impressions 
Scale (CGI), OCD Visual Analogue Scale (OCD-VAS), Yale-Brown Obsessive Compulsive Challenge 
Scale (YBOCCS), and vital signs. This will be pilot data to help us evaluate patient satisfaction, ongoing 
safety, and maintenance of response.
You can upload charts or diagrams if any
Criteria for Early Discontinuation  
Criteria for Early Discontinuation
 Participants are free to withdraw from the study at any time for any reason. Study doctors are to discontinue 
participants from the study if participants:
Request early discontinuation or withdraw consent.
Experience a serious or intolerable adverse event that prevents the participant from continuing. 
In the study clinician's opinion are evaluated to be much worse (CGI-I score of 6) for two 
consecutive visits. If the participant begins to show clinical deterioration during the 14-day treatment 
phase and further continuation under such circumstances would be detrimental to the participant, a 
referral will be made for a clinical evaluation by an independent evaluator to determine whether the 
participant should be withdrawn from the study. 
In the study clinician's opinion are experiencing clinically significant deterioration in a comorbid 
condition such as major depression. For example, if a participant became suicidal or their symptoms 
of depression increased such that the depressive symptoms were much or very much worse relative 
to baseline and the CDRS is no longer <60, they would be discontinued from the study. 
Are lost to follow-up.
Encounter other conditions (such as administrative issues or pregnancy).
If the participant discontinues from the study at any time at his/her own request or at the study doctor's 
request, the reason(s) for discontinuation will be recorded by the study. Participants who have received 
ketamine and withdraw during the 14-day treatment phase will be asked to return to the study site for final 
safety assessments and scheduled for the final study visit. Participants withdrawing from the study for 
reasons related to the study medication (usually adverse events) will be followed until the event(s) have 
resolved or no further action is required.
 
If a participant is withdrawn from the protocol, they will be eligible for up to three months of no cost 
treatment on the Children’s Day Unit. They will also have the option to attend the school program on the 
CDU. If the participant or the participant’s parent/guardian would prefer outside referrals, arrangements will 


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be made by the research staff. The psychiatrist has full responsibility and authority to refer the participant 
for this clinical evaluation at any time regarding the participant’s suitability for remaining in the study.
 
Blood and other Biological Samples
Please create or insert a table describing the proposed collection of blood or other biological specimens
A blood sample, approximately one tablespoon (15 cc’s) of blood, will be taken at screening and at study 
completion (or withdrawal, if earlier) for a total of two tablespoons (30 cc). These samples will be used for 
safety monitoring, including Chemistry Screen and CBC. The samples will be forwarded to a centralized 
laboratory for analysis. Participants may experience a bruise at the site of venipuncture. EMLA cream may 
be used to minimize the discomfort of venipuncture.
Assessment Instruments
Create a table or give a brief description of the instruments that will be used for assessment
Anxiety Disorders Interview Schedule for Children for DSM-IV (ADIS-C/P Revised): This will be 
administered to the subject (and parent/caretaker for those <18 and those 18-22 with permission) by the 
independent evaluator (IE) at screening to confirm the diagnosis of OCD and its age of onset. 
 
Yale-Brown Obsessive Compulsive Scale, Child version (CYBOCS): The CYBOCS is a
semi-structured measure of OCD severity with excellent inter-rater reliability, internal consistency, and test-
retest reliability. It is validated in those starting at age 7 and used in studies up to age 20. The CYBOCS 
differs from the adult YBOCS only in its use of simpler language. The CYBOCS will be administered by IE 
at screening and 120 minutes post-infusion to determine OCD severity. The CYBOCS will also be 
administered by IE at baseline, day 7, and day 14 and will be the primary outcome measure. As secondary 
outcomes, response will be defined as a CYBOCS decrease of ≥ 30% and excellent response as a CYBOCS 
of ≤ 10 following the Pediatric OCD Treatment Study (2004). The CYBOCS checklist will be used to 
determine symptom dimensions.
 
Children’s Depression Rating Scale-Revised (CDRS-R): The CDRS-R is a 17-item clinician-administered 
semi-structured interview with good inter-rater reliability and validity that assesses 17 symptom areas 
related to depression, including those that serve as criteria in the DSM-IV. It provides an overall index of 
severity of depression. This assessment will be administered by IE at screening and 120 minutes post-
infusion and by IE at baseline, day 7 and day 14.
 


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Clinical Global Impressions Scale (CGI): This is a clinician rated instrument providing a
single score for severity and improvement (from a 7-point scale) comparing the patient’s condition during 
each visit on treatment to the condition at baseline (before treatment).  The CGI will be administered by 
both IE and the study MD as per the study flow chart.
 
Columbia-Suicide Severity Rating Scale (C-SSRS): This is a semi-structured clinician rating of
suicidal behavior, suicide attempts, and presence and intensity of suicidal ideation. The assessment will be 
administered by study MDs at screening, baseline, day 3 or 4, day 7, and day 14.
 
Young Mania Rating Scale (YMRS): YMRS is an 11- item clinician administered scale for rating manic 
symptoms. It will be administered by the study MD at baseline, 120 minutes post-infusion, day 3 or 4, day 
7, and day 14.
 
Clinician Administered Dissociative States Scale (CADSS): This is a clinician rated instrument for rating 
degree of dissociation. A severity scale will be added: mild, moderate, severe for those items endorsed on 
interview. It will be administered by the study MD at baseline, 20 minutes from the start of the infusion, 
immediately post-infusion, 60 and 120 minutes post-infusion, day 3 or 4, day 7, and day 14. 
 
Brief Psychiatric Rating Scale (BPRS): The BPRS is an 18-item observer-scale designed to assess patients 
with major psychiatric disorders, particularly schizophrenia. The BPRS measures positive symptoms, 
general psychopathology and affective symptoms. Some items (e.g. mannerisms and posturing) can be rated 
simply on observation of the patient; other items (e.g. anxiety) involve an element of self-report by the 
patient. The BPRS is administered by a trained clinician via a semi-structured interview at baseline, 120 
minutes post-infusion, day 3 or 4, day 7, and day 14. 
 
OCD Visual Analogue Scale (OCD-VAS): A one-item scale to assess OCD symptoms over a rapid time 
frame. Patients will be asked to report their rating on this scale prior to, during and after the infusion as per 
the study flowchart. 
 
Child Obsessive-Compulsive Impact Scale-Revised (COIS-R): This 27-item self-report
questionnaire measures OCD-specific functional impairment. The COIS-R-C is a 3-factor structure youth-
report form. The COIS-R-P is a 4-factor structure parent-report measure (completed by the parent/caretaker 
for those <18 and those 18-22 with permission). Participants and their parents will be asked to complete the 
COIS-R at baseline, day 7, and day 14. 
 
Yale-Brown Obsessive Compulsive Challenge Scale (YBOCCS): A brief self-report
scale to assess rapid changes in OCD symptoms. Patients will be asked to report their rating on this scale 
prior to, during and after the infusion as per the study flowchart. 
 


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Family History Screen (FHS): This screens for the presence of 15 psychiatric disorders among the 
participant’s biological relatives. It is administered to a family informant (for those ages 8-17) or to the 
subject (ages 18-22), who reports on himself/herself and on other biological relatives. It will be 
administered by the MD at screening.
 
Social Communication Questionnaire (SCQ): This is a 40 item yes-or-no parent questionnaire to screen for 
autism spectrum disorders.
DSM-IV OCPD Assessment: This is a semi-structured interview that assesses for symptoms of Obsessive 
Compulsive Personality Disorder. 
Please attach copies, unless standard instruments are used
Off label and investigational use of drugs/devices
Choose from the following that will be applicable to your study 
   Drug
Select the number of drugs used in this study
1
Drug #1
Name of the drug 
Ketamine
Manufacturer and other information
Ketamine
Approval Status
No IND is required
Choose one of the following options
FDA conditions are met (see 'Rules')
Explain
We completed the IND Decision Worksheet and it appears that we do not need to apply for an IND 
exception. The IND Decision Worksheet was previously uploaded for review. 
Research Related Delay to Treatment
Will research procedures result in a delay to treatment?
Yes
Maximum duration of delay to any treatment 
For enrolled participants that do not require a medication washout, there will be no delay to receiving 
treatment. For enrolled participants that require a medication washout, the maximum delay in initiating 
study treatment will be two weeks. 
Maximum duration of delay to standard care or treatment of known efficacy


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For all enrolled participants, the maximum delay to standard care or treatment of known efficacy will be 14 
days.
Treatment to be provided at the end of the study
Upon completion of the acute 14-day treatment period, participants will be offered three additional months 
of open treatment for OCD (medication management and/or CBT) at no cost. This treatment will be offered 
to all participants regardless of response during the acute study treatment period. For participants requiring 
continued OCD treatment following this three-month follow-up period, the research staff will refer the 
patient to his or her previous providers or will assist the participant and his/her family in identifying new 
treatment providers.
Clinical Treatment Alternatives
Clinical treatment alternatives
Currently cognitive-behavioral treatment involving exposure and response prevention (CBT/ERP) and 
serotonin reuptake inhibitor (SRI) medication are considered the first line treatments for OCD. However, 
pharmacotherapies have relatively modest effects in OCD. CBT/ERP treatment is the mainstay of the 
treatment for OCD. CBT/ERP alone results in response rates of anywhere between 60% and 80%, but fear 
of and non-adherence to CBT/ERP are hypothesized to serve as barriers to the treatment's efficacy. Subjects 
will have these treatments explained to them by the study doctor, and they will be offered the option to 
receive referrals for one or both of these treatments rather than participating in the study.
Risks/Discomforts/Inconveniences 
Risks that could be encountered during the study period
Risks associated with participation are: 1) distress from discussion about emotional symptoms; 2)
blood sampling; 3) clinical deterioration due to being off medication; and 4) medication-related adverse 
events and side effects from ketamine infusion; 5) medication-related adverse events and side effects from 
Zofran, Ativan, Haldol, Cogentin and Nitroglycerin.  
 
1) Distress from thoughts or discussion about emotional symptoms: Some participants may experience 
distress or anxiety related to participating in these procedures. Participants will be monitored throughout the 
procedures, and they will be encouraged to report any concerns. A psychiatrist will be available to assist the 
participant if needed, and participants will be removed from the protocol if their distress or anxiety becomes 
intolerable. Participants and their legal guardians will be informed that their continued treatment at NYSPI 
will not be impacted if at any point they choose to no longer participate.
 
2) Risks of blood sampling: A blood sample, approximately one tablespoon (15 cc’s) of blood, will be 
taken at screening and at study completion (or withdrawal, if earlier) for a total of two tablespoons (30 cc). 
These samples will be used for safety monitoring, including Chemistry Screen and CBC. The samples will 
be forwarded to a centralized laboratory for analysis. Participants may experience a bruise at the site of 
venipuncture. EMLA cream may be used to minimize the discomfort of venipuncture.
 


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3) Risks of being off medication: In order to participate in this study, participants need to be off all 
psychotropic medications other than SRI medications for two weeks prior to study procedures. This carries 
the risk of the participant's OCD symptoms worsening, becoming more depressed, and worsening of other 
symptoms including feeling suicidal or risk of suicide. Medications will be slowly stopped in a safe manner 
as directed by the study doctor, who will work with the participant's present treating doctor. Participants will 
closely be monitored during this medication washout period and they will be offered other medications for 
relief from sleeplessness and anxiety as needed. If the participant or study doctor feel that he or she cannot 
tolerate further delay in treatment, they will be withdrawn from the study and treated with known OCD 
medications. 
 
4) Ketamine risks: Ketamine is FDA approved as an anesthetic in surgical procedures at higher doses (6 
mg/kg for induction in children and adolescents) than the doses being used in this study 11 and has also been 
used safely in the management of chronic pain in the pediatric population 12, 13. In this study, ketamine will 
be carefully administered through an infusion and patients will be continuously monitored by a study 
physician. The dose of 0.5mg/kg has been safely administered to children and adolescents without adverse 
side effects in multiple prior studies of ketamine.17,18
 
The following risks might be associated with ketamine:
Based on data from the study conducted by Rodriguez and colleagues 14 on ketamine for the 
treatment of adult OCD,  there is a chance that the participant might experience some distress if 
his/her OCD symptoms begin to return after the infusion. To minimize this distress, study staff will 
check in with the participant and their family daily and all participants will be offered up to three 
months of front-line treatment for OCD at no cost after the study. 
Ketamine may produce temporary symptoms, including vivid dreams, feeling like you are floating 
above your own body, that your surroundings are strange, or seeing/hearing things that are not there 
(illusions/hallucinations). For this reason, any patients with current or past symptoms of psychosis 
will not be permitted to enroll in this study. Ketamine may also cause temporary (lasting at most 1-2 
hours after being given ketamine) increased libido (sex drive), euphoria (happy mood), increased 
thirst, metallic taste, upset stomach, or heachache. Participants will be monitored closely for side 
effects during and after the infusion. 
Ketamine may produce hypersalivation, nausea and in some cases vomiting. Experienced study 
doctors will be on site to take care of the participant in the rare case that this should happen.
Ketamine can cause mild increases in your heart rate or blood pressure. Study doctors will closely 
monitor the participant's heart rate and blood pressure during the ketamine administration.
There is a theoretical risk that exposure to ketamine may predispose susceptible subjects to 
subsequent abuse of this drug. For this reason, participants with a history or substance abuse or 
dependence will be asked not to participate. 
Participants should not drive a car or engage in hazardous activities for at least 24 hours after the 
ketamine dose. Research staff will regularly contact the participant (and parent, if applicable) by 
telephone during the week to check on any possible consequences of having participated in the 
study.


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Should uncomfortable feelings or thoughts occur, the ketamine infusion can be stopped, and the study 
discontinued. We will also stop the study for any reason at the parent or participant's request, or if we 
observe that the participant is experiencing bad effects from ketamine.
 
Safety and Termination of Ketamine Infusion:
In case of nausea or anxiety, patients can be administered anti-nausea medications, such as Zofran (a 
medication that helps to decrease nausea), or anxiolytics such as Ativan (a medication that helps to decrease 
nervousness) from the pharmacy formulary. In the rare event of severe agitation, Haldol (an antipsychotic 
medication that helps decrease severe impulsive behaviors and uncontrolled movements), Ativan and 
Cogentin (a medication that helps with the side effects of Haldol) can be administered as well. The common 
and severe side effects of Zofran, Ativan, Haldol and Cogentin are described below:
Zofran- Most common side effects: Constipation, diarrhea, increased liver enzymes, headache, fatigue and 
malaise. Severe side effects: Serious arrhythmia such as Torsades de pointes and prolonged QT interval 
(changes in heart rhythm).
Ativan- Most common side effects: Asthenia (weakness), dizziness, sedation, unsteadiness and depression. 
Severe side effect: Delirium.
 
Glycopryolate- Most common side effects: Flushing, constipation, vomiting, xerostomia,
headache, urinary tract infectious disease, nasel congestion, and nasopharyngitis. Serious
side effects: Bradyarrhythmia, cardiac arrest, cardiac dysrhythmia, tachycardia, ventricular
fibrillation, malignant hyperthermia, nystagmus, seizure, respiratory arrest. 
 
Haldol- Most common side effects: Constipation, xerostomia (dry mouth), dystonia (abnormal movements), 
extrapyramidal disease (neurological symptoms such as: abnormal mood, stiffness, and tic like behaviors), 
somnolence and blurred vision. Severe side effects: Serious arrhythmia such as Torsades de pointes and 
prolonged QT interval (changes in heart rhythm), agranulocytosis (significant decrease in white blood cells), 
seizure, tardive dyskinesia (abnormal neural movements), priapism (abnormal erection), and pulmonary 
embolism (blood clot in lungs).
Cogentin- Most common side effects: Tachycardia (heart racing), constipation, nausea, xerostomia (dry 
mouth), blurred vision, dysuria (painful urination), urinary retention (difficulty urinating). Severe side 
effects: Anhidrosis (dryness in the skin), heat stroke (increased body temperature), paralytic ileus (bowel 
dysfunction), confusion, disorientation, drug-induced psychosis and visual hallucinations.
 
In case of very high blood pressure during the ketamine infusion, the infusion will be stopped; patients 
blood pressure will be monitored and if there is no decrease after 5 minutes, then either
Clonidine, 0.05-0.1mg x 1 or one dose of sublingual nitroglycerin, 0.3 mg, will be administered. If patients 
experience blurred vision, headache or chest pain as a result of high blood pressure or any other medical 
complications, urgent care will be provided. The ketamine infusion will be terminated if patients complain 
of any uncomfortable symptoms of rising anxiety and agitation, or any other uncomfortable symptoms. The 
common and severe side effects of nitroglycerin are described below:
 


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Clonidine- Most common side effects: Contact dermatitis, erythema, pruritus, xerostomia,
dizziness, headache, sedation, somnolence and fatigue. Severe side effects:
Atrioventricular block.
 
Nitroglycerin- Most common side effects: Hypotension (low blood pressure), flushing (redness in the face), 
headache and lightheadedness. Severe side effects: Anaphylactoid reaction (allergic reactions), 
methemoglobinemia (changes in the structure of hemoglobin), raised intracranial pressure (increased 
pressure in the fluid of the central nervous system).
Describe procedures for minimizing risks
All efforts will be made to minimize risks and to ensure participant safety. Participants will be encouraged 
to relay the emergence of any adverse events to the study team, who will attend to it appropriately. We have 
taken steps to ensure the safety of subject from these safety issues in the following ways:
 
a) Patients will be assessed and monitored frequently during and immediately after the infusion, as well as 
for two hours post-infusion  with assessments by study physicians (i.e. vital signs, scales of psychosis and 
dissociation)
 
b) Patients with medical and psychiatric co-morbidity that makes participation unsafe or vulnerability to 
psychosis (past history of psychosis or family member with schizophrenia) will not be eligible.
 
c) Patients with history of substance dependence or history of substance abuse in the prior year will be 
excluded.
 
d) Patients with any adverse events associated with the infusion will be hospitalized, if needed.
 
e) Since relief from OCD symptoms is expected to be temporary for some participants after the ketamine 
infusion, all participants will be offered up to three months of  front-line treatment for OCD with 
medications and/or CBT at no cost, regardless of their response to the ketamine infusion.
Methods to Protect Confidentiality
Describe methods to protect confidentiality
Confidentiality will be maintained by assigning unique identifying code numbers to each participant and 
his/her family. Code numbers, rather than names, will be used on all documents pertaining to the 
participants. All data will be kept in locked files or on Windows 2003 servers or XP workstations with 
password access, to which only researchers will have access. These operating systems provide multi-level 
security restrictions and privileges will only be granted by Drs. Rynn, Simpson and to others working on the 
project. All individuals granted access to the database will be issued a password. The portion of the database 
that connects a person’s identifying information and the code numbers will be maintained separately and 


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require a higher level of security clearance on the system. No individual will be named or described with 
information that could allow him/her to be identified in published reports.
Clinical data will be entered into a Microsoft Access relational database, checked for consistency. This 
database is stored on a network server securely located behind the NYSPI firewall; a username and 
password are required to access the server and a separate password to access this database. Subjects are 
identified by numeric codes consistent with HIPAA guidelines; hard copies of data are stored in locked 
rooms with restricted access. The data manager will perform random data audits to further ensure the 
integrity of the data. Server backups of study databases are performed nightly; database copies on CD-ROM 
archive disks are stored separately for safety. Drs. Simpson and Rynn will oversee the operation and 
scientific integrity of the clinical trial and ensure that the protocol design, instrumentation, patient 
recruitment, data collection and analysis yield information that achieves the major objectives of the study.
Will the study be conducted under a certificate of confidentiality?
No
Direct Benefits to Subjects  
Direct Benefits to Subjects
The potential benefit of this study is that the participant may respond to this novel treatment strategy for 
OCD. In a recent study of adults with OCD, ketamine was associated with an immediate remission of 
clinical symptoms, and this improvement was maintained in some adults for up to 1 week. 14 In addition, 
each participant will be receiving a thorough psychiatric evaluation and will be carefully followed in the 
study. After completion of the study, participants will receive up to 3 months of no-cost OCD treatment 
(medication management and/or CBT) from the study team. 
Compensation and/or Reimbursement 
Will compensation or reimbursement for expenses be offered to subjects?
Yes
Please describe and indicate total amount and schedule of payment(s). 
Include justification for compensation amounts and indicate if there are bonus payments.
Participants will be compensated $75 for the evaluations done at the time of the infusion, and $50 for 
assessments completed at each of the three subsequent in-person visits, for a total compensation of up to 
$225. The compensation takes into account the time involved, travel costs and parking in New York City, 
and meals or snacks.
References


Protocol Summary Form
7023
Goldberg, Pablo
Page 28 of 30
References
pasting1. Rauch SL, Wedig MM, Wright CI, et al. Functional magnetic resonance imaging study of regional 
brain activation during implicit sequence learning in obsessive-compulsive disorder. Biol Psychiatry. Feb 1 
2007;61(3):330-336.
2. Atmaca M, Yildirim H, Ozdemir H, Tezcan E, Poyraz AK. Volumetric MRI study of key brain regions 
implicated in obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. Jan 30 
2007;31(1):46-52.
3. Graybiel AM, Rauch SL. Toward a neurobiology of obsessive-compulsive disorder. Neuron. Nov 
2000;28(2):343-347.
4. Chakrabarty K, Bhattacharyya S, Christopher R, Khanna S. Glutamatergic dysfunction in OCD. 
Neuropsychopharmacology. Sep 2005;30(9):1735-1740.
5. Rosenberg DR, MacMaster FP, Keshavan MS, Fitzgerald KD, Stewart CM, Moore GJ. Decrease in 
caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine. 
J. Am. Acad. Child Adolesc. Psychiatry. Sep 2000;39(9):1096-1103.
6. Rodriguez CI, Bender J, Jr., Marcus SM, Snape M, Rynn M, Simpson HB. Minocycline augmentation of 
pharmacotherapy in obsessive-compulsive disorder: an open-label trial. J Clin Psychiatry. Sep 
2010;71(9):1247-1249.
7. Coric V, Milanovic S, Wasylink S, Patel P, Malison R, Krystal JH. Beneficial effects of the
antiglutamatergic agent riluzole in a patient diagnosed with obsessive-compulsive disorder and major 
depressive disorder. Psychopharmacology (Berl). May 2003;167(2):219-220.
8. Stewart SE, Jenike EA, Hezel DM, et al. A single-blinded case-control study of memantine in severe 
obsessive-compulsive disorder. J Clin Psychopharmacol. Feb 2010;30(1):34-39.
9. Hezel DM, Beattie K, Stewart SE. Memantine as an augmenting agent for severe pediatric OCD. Am J 
Psychiatry. Feb 2009;166(2):237.
10. Rynn M, Puliafico A, Heleniak C, Rikhi P, Ghalib K, Vidair H. Advances in Pharmacotherapy for 
Pediatric Anxiety Disorders. FOCUS: The Journal of Lifelong Learning in Psychiatry. June 2011;9(3): 299-
310.
11. Kararmaz A, Kaya S, Turhanoglu S, Ozyilmaz MA. Oral ketamine premedication can prevent 
emergence agitation in children after desflurane anaesthesia. Pediatr Anaesth. June 2004;14(6): 477-482.
12. Dahmani S, Michelet D, Abback PS, et al. Ketamine for perioperative pain management in children: a 
meta-analysis of published studies. Pediatric Anesthesia. Feb 2011;21(6):636–652. 
13. Finkel JC, Pestieau SR, Quezado Z. Ketamine as an adjuvant for treatment of cancer pain in children 


Protocol Summary Form
7023
Goldberg, Pablo
Page 29 of 30
and adolescents. The Journal of Pain. June 2007;8(6):515-521.
14. Rodriguez CI, Kegeles LS, Levinson A, et al. Randomized controlled crossover trial of ketamine in 
obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology. July 2013;38(12): 2475-
2483.
15. Bloch MH, Wasylink S, Landeros-Weisenberger A, et al. Effects of ketamine in treatment-refractory 
obsessive-compulsive disorder. Dec 2012;72(11):964-70
16. Loo, CK, Gálvez V, O'Keefe E, et al. Placebo-controlled Pilot Trial Testing Dose Titration and 
Intravenous, Intramuscular and Subcutaneous Routes for Ketamine in Depression. Acta Psychiatrica 
Scandinavica July 2016;134(1):48-56. 
17. Singh JB, Fedgchin M, Daly EJ, et al. A Double-Blind, Randomized, Placebo-Controlled, Dose-
Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression. American 
Journal of Psychiatry. Aug 2016: 173(8):816-26.
18. Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients. 
Biological psychiatry. Feb 2000;47(4):351-354.
19. Zarate CA, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in 
treatment-resistant major depression. Archives of general psychiatry. Aug 2006;63(8):856-864.
20. Marcus RJ, Victoria BA, Rushman SC, Thompson JP. Comparison of ketamine and morphine for 
analgesia after tonsillectomy in children. Br J Anaesth. Feb 2000; 84(6):739-742.
21. Aspinall RL, Mayor A. A prospective randomized controlled study of the efficacy of ketamine for 
postoperative pain relief in children after adenotonsillectomy. Paediatr Anaesth. May 2001;11(3):333-336.
22. Team POTS. Cognitive-behavior therapy, sertraline, and their combination for children and adolescents 
with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled 
trial. JAMA. Oct 27 2004;292(16):1969-1976.
23. Bloch, M. H., Landeros-Weisenberger, A., Kelmendi, B., Coric, V., Bracken, M. B., & Leckman, J. F. 
(2006). A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive 
disorder. Molecular psychiatry, 11(7), 622-632.
24. Correll, C. U. (2007). Assessing and maximizing the safety and tolerability of antipsychotics used in the 
treatment of children and adolescents. The Journal of clinical psychiatry, 69, 26-36.
25. Papolos, D. F., Teicher, M. H., Faedda, G. L., Murphy, P., & Mattis, S. (2013). Clinical experience 
using intranasal ketamine in the treatment of pediatric bipolar disorder/fear of harm phenotype. Journal of 
affective disorders, 147(1), 431-436.


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Page 30 of 30
Uploads
Upload the entire grant application(s)
Upload copy(ies) of unbolded Consent Form(s)
OCD Ketamine_Young Adult Consent Form_UNBOLDED_8.30.17.pdf
OCD Ketamine_Parent of Young Adult Consent Form_UNBOLDED_8.30.17.pdf
OCD Ketamine_Parent Consent Form_UNBOLDED_8.30.2017.pdf
Upload copy(ies) of bolded Consent Form(s)
Upload copy(ies) of unbolded Assent Form(s)
OCD Ketamine_Adolescent_ Assent_ Form_UNBOLDED_8.30.2017.pdf
Upload copy(ies) of bolded Assent Form(s)
Upload copy(ies) of the HIPAA form
HIPAA_Child_Authorization_8.30.17.pdf
HIPAA_Adult_Authorization_8.30.17.pdf
Upload any additional documents that may be related to this study
IE Assessment of OCPD.pdf
OCD Ketamine Study Flowchart for PSF_Updated_11.30.15.pdf
OCD Phone Screen #7023_Updated_12.22.16.pdf
IRB7023_OCD Ketamine Recruitment_Brochure_Updated_8.15.17.pdf
IRB7023_OCD_Ketamine_Recruitment_Flyer_Updated_12.14.17.pdf
IRB7023_OCD Ketamine Recruitment_Short Study Blurb_Updated_12.21.17.pdf
IRB7023_OCD Ketamine Recruitment_Long Study Blurb_Updated_12.21.17.pdf

SAP_001.pdf: 
Page 1 of 6 
 
 
STATISTICAL ANALYSIS PLAN (SAP) 
 
Study title 
Ketamine Treatment for Pediatric-Refractory Obsessive-
Compulsive Disorder (OCD) 
Principal investigator  
Pablo H. Goldberg, M.D. 
 
 
 
 
Associate Clinical Professor of Psychiatry 
 
 
 
 
New York State Psychiatric Institute/Columbia University 
 
 
 
 
New York, NY 
Protocol ID 
 
 
37023 
ClinicalTrials.gov ID  
NCT02422290 
Version 
 
 
1 (3/13/2013) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Page 2 of 6 
SIGNATURE 
 
Principal Investigator  
 
____________________________ 
 
 
 
 
 
 
     Pablo H. Goldberg, MD 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Page 3 of 6 
 
 
CONTENTS 
SIGNATURE .................................................................................................................................. 2 
1   INTRODUCTION ..................................................................................................................... 4 
2   AIMS ......................................................................................................................................... 4 
3   PROCEDURES ......................................................................................................................... 4 
4   ANALYSIS SET ........................................................................................................................ 5 
5   OUTCOMES ............................................................................................................................. 5 
6.1.   Primary Outcomes .............................................................................................................. 5 
6.2.   Secondary Outcomes .......................................................................................................... 5 
6.3   Adverse Outcomes .............................................................................................................. 5 
6   STATISTICAL ANALYSIS ..................................................................................................... 5 
8.1.   Descriptive Statistics .......................................................................................................... 5 
8.2.   Statistical Tests ................................................................................................................... 5 
7   MISSING VALUES .................................................................................................................. 6 
8   REFERENCES .......................................................................................................................... 6 


Statistical Analysis Plan 
Page 4 of 6 
 
1   INTRODUCTION 
We will evaluate the feasibility/tolerability, and preliminary efficacy of ketamine, a medication 
that modulates glutamate in the brain, as a rapid treatment for OCD symptoms in adolescents 
with OCD. Our rationale for using ketamine is threefold. First, glutamatergic abnormalities in 
corticostriatal circuits may underlie OCD symptoms based on human imaging, genetic, and 
animal studies; striatal glutamatergic levels have been associated with OCD severity. Thus, 
medications that modulate glutamatergic neurotransmission (e.g., riluzole memantine, 
minocycline) may be effective. Second, riluzole and memantine have shown promise for OCD in 
case reports or open trials, but neither is FDA-approved for use in children; riluzole also has 
significant liabilities in terms of adverse events and cost. In contrast, ketamine is FDA-approved 
for anesthesia in children, adolescents and adults, and is routinely used at higher doses than 
proposed in this study. It is also used as adjunctive pain management for children and 
adolescents suffering from end stage medical illness. Third, we found in a small randomized 
controlled trial that unmedicated OCD adult patients had a near cessation of obsessional thoughts 
during an intravenous ketamine infusion; these effects were maintained in half of patients for up 
to one week (Rodriguez et al. 2013). These exciting findings lead to two questions: 1) is this type 
of study acceptable and feasible in youth; 2) are ketamine’s effects similar in adolescents and 
young adults? 
2   AIMS 
We propose a pilot study to determine the acceptability, feasibility and potential efficacy of a 
single ketamine infusion in adolescents and young adults with OCD. Promising data will lead to 
a grant application to the National Institutes of Mental Health for a full scale randomized 
controlled trial. 
 
Aim 1. To assess the feasibility/tolerability of using ketamine in adolescents with OCD 
 
Aim 2. To assess the effects of ketamine on OCD severity 
3   PROCEDURES 
We will recruit 5 adolescents and young adults (post-pubertal, ages 14-20) with OCD using 
similar criteria as in our prior ketamine study (Rodriguez et al. 2013) with the modification that 
participants have attempted at least one trial of a standard treatment (i.e., SRI and/or CBT). They 
will be free of medication and have at least moderate OCD severity (rating on Children’s Yale-
Brown Obsessive-Compulsive Scale [CY-BOCS] of at least 16) and near constant obsessions. 
After baseline assessment and evaluation, patients will receive a single infusion of intravenous 
ketamine 0.5 mg/kg. Obsessional severity will be evaluated at baseline, during the ketamine 
infusion and during post-infusion observation using the OCD-Visual Analogue Scale; OCD and 
depressive severity will be evaluated using the CY-BOCS (child version) and Children’s 
Depression Rating Scale Revised at weekly intervals for 2 weeks after infusion.  


 
Page 5 of 6 
4   ANALYSIS SET 
This pilot study is a non-controlled clinical trial consisting of one group of participants. 
Participants will be adolescents and young adults with OCD who have failed at least one trial of 
standard treatment. All participants will receive an intravenous ketamine infusion.  
5   OUTCOMES 
6.1.   Primary Outcomes 
i. 
Total number of screened participants 
ii. 
Total number completing  
 
6.2.   Secondary Outcomes 
i. 
CY-BOCS score at baseline, 1 week post-infusion, and 2 weeks post infusion 
ii. 
Children’s Depression Rating Scale Revised at baseline, 1 week post-infusion, 
and 2 weeks post 
6.3   Adverse Outcomes 
i. Adverse events will be assessed throughout the study period 
ii. Suicidality will be obtained with the Columbia-Suicide Severity Rating Scale (C-
SSRS). 
6   STATISTICAL ANALYSIS  
Data will be analyzed using IBM SPSS. We will report descriptive statistics for all outcomes 
including mean and standard deviation.  
8.1.   Descriptive Statistics 
For acceptability and feasibility, we will assess the number screened and the number completed 
by reporting total numbers and percentages.   
8.2.   Statistical Tests 
For potential efficacy, continuous outcomes will be modeled as a function of time using mixed-
effects regression, and the proportion of responders (CY-BOCS decrease ≥ 35%) and remitters 
(CY-BOCS ≤ 12) one and two weeks after the ketamine infusion will be computed. Differences 
in outcomes from baseline to 1 week post-infusion and 2 weeks post-infusion will be the 
independent variables. Study subjects will be considered as random effects and the proportion of 
responders and remitters as well as the difference of obsessional severity from baseline to post-
infusion will be included as fixed effects. Sex and age will be considered as covariates. 95% 
confidence intervals, and p-values will be presented for each outcome variable and time point


Statistical Analysis Plan 
Page 6 of 6 
 
7   MISSING VALUES 
Mixed models provide adequate power without ad hoc imputations (Chakraborty & Gu, 2009). 
Thus, missing value will not be imputed.  
8   REFERENCES 
Rodriguez, C.I., Kegeles, L.S., Levinson, A., Feng, T., Marcus, S.M., Vermes, D., …, & Simpson 
 
H.B. (2013). Randomized controlled crossover trial of ketamine in obsessive-compulsive 
 
disorder: proof-of-concept. Neuropsychopharmacology, 38(12), 2475-2483. 
Chakraborty, H. & Gu, H. (2009). A Mixed Model Approach for Intent-to-Treat Analysis in 
 
Longitudinal Clinical Trials with Missing Values. RTI Press Publication No. MR-0009-
 
0903. Research Triangle Park, NC: RTI Press 
 
 


Statistical Analysis Plan 
Page 1 of 6 
 
STATISTICAL ANALYSIS PLAN (SAP) 
 
Study title 
Ketamine Treatment for Pediatric-Refractory Obsessive-
Compulsive  Disorder (OCD) 
Principal investigator  
Pablo H. Goldberg, M.D. 
 
 
 
 
Associate Clinical Professor of Psychiatry 
 
 
 
 
New York State Psychiatric Institute/Columbia University 
 
 
 
 
New York, NY 
Protocol ID 
 
 
37023 
ClinicalTrials.gov ID  
NCT02422290 
Version 
 
 
2 (01/20/2020) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Page 2 of 6 
SIGNATURE 
 
Principal Investigator  
 
____________________________ 
 
 
 
 
 
 
     Pablo H. Goldberg, MD 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Page 3 of 6 
 
 
CONTENTS 
SIGNATURE .................................................................................................................................. 8 
1   INTRODUCTION ................................................................................................................... 10 
2   AIMS ....................................................................................................................................... 10 
3   PROCEDURES ....................................................................................................................... 10 
5   ANALYSIS SET ...................................................................................................................... 11 
6   OUTCOMES ........................................................................................................................... 11 
6.1.   Primary Outcomes ............................................................................................................ 11 
6.2.   Secondary Outcomes ........................................................................................................ 11 
6.3   Adverse Outcomes ............................................................................................................ 11 
7   STATISTICAL ANALYSIS ................................................................................................... 11 
8.1.   Descriptive Statistics ........................................................................................................ 11 
8.2.   Statistical Tests ................................................................................................................. 11 
8   MISSING VALUES ................................................................................................................ 12 
9   REFERENCES ........................................................................................................................ 12 


Statistical Analysis Plan 
Page 4 of 6 
 
1   INTRODUCTION 
We will evaluate the feasibility/tolerability, and preliminary efficacy of ketamine, a medication 
that modulates glutamate in the brain, as a rapid treatment for OCD symptoms in adolescents 
with OCD. Our rationale for using ketamine is threefold. First, glutamatergic abnormalities in 
corticostriatal circuits may underlie OCD symptoms based on human imaging, genetic, and 
animal studies; striatal glutamatergic levels have been associated with OCD severity. Thus, 
medications that modulate glutamatergic neurotransmission (e.g., riluzole memantine, 
minocycline) may be effective. Second, riluzole and memantine have shown promise for OCD in 
case reports or open trials, but neither is FDA-approved for use in children; riluzole also has 
significant liabilities in terms of adverse events and cost. In contrast, ketamine is FDA-approved 
for anesthesia in children, adolescents and adults, and is routinely used at higher doses than 
proposed in this study. It is also used as adjunctive pain management for children and 
adolescents suffering from end stage medical illness. Third, we found in a small randomized 
controlled trial that unmedicated OCD adult patients had a near cessation of obsessional thoughts 
during an intravenous ketamine infusion; these effects were maintained in half of patients for up 
to one week (Rodriguez et al. 2013). These exciting findings lead to two questions: 1) is this type 
of study acceptable and feasible in youth; 2) are ketamine’s effects similar in adolescents and 
young adults? 
2   AIMS 
We propose a pilot study to determine the acceptability, feasibility and potential efficacy of a 
single ketamine infusion in adolescents and young adults with OCD. Promising data will lead to 
a grant application to the National Institutes of Mental Health for a fullscale randomized 
controlled trial. 
 
Aim 1. To assess the feasibility/tolerability of using ketamine in adolescents with OCD 
 
Aim 2. To assess the effects of ketamine on OCD severity 
3   PROCEDURES 
We will recruit 5 adolescents and young adults (post-pubertal, ages 14-20) with OCD using 
similar criteria as in our prior ketamine study (Rodriguez et al. 2013) with the modification that 
participants have attempted at least one trial of a standard treatment (i.e., SRI and/or CBT). They 
will be free of medication and have at least moderate OCD severity (rating on Children’s Yale-
Brown Obsessive-Compulsive Scale [CY-BOCS] of at least 16) and near constant obsessions. 
After baseline assessment and evaluation, patients will receive a single infusion of intravenous 
ketamine 0.5 mg/kg. Obsessional severity will be evaluated at baseline, during the ketamine 
infusion and during post-infusion observation using the OCD-Visual Analogue Scale; OCD 
severity will be evaluated using the Children’s Yale-Brown Obsessive Compulsive Scale (CY-


Statistical Analysis Plan 
Page 5 of 6 
BOCS) and Yale-Brown Obsessive Compulsive Challenge Scale (Y-BOCCS) at weekly intervals 
for 2 weeks and 3-months following after the infusion; illness severity will be rated using the 
Clinical Global Impressions Severity Scale (CGI-S) at weekly intervals for 2 weeks and 3-
months following after the infusion. 
5   ANALYSIS SET 
This pilot study is a non-controlled clinical trial consisting of one group of participants. 
Participants will be adolescents and young adults with OCD who have failed at least one trial of 
standard treatment. All participants will receive an intravenous ketamine infusion.  
6   OUTCOMES 
6.1.   Primary Outcomes 
Primary outcomes will be the changes in the CY-BOCS total score and CGI-S rating from 
baseline to 14 days post infusion.  
6.2.   Secondary Outcomes 
Secondary outcomes will be the changes in the OCD-VAS and Y-BOCCS total score from 
baseline to 14 days post infusion.  
6.3   Adverse Outcomes 
Adverse events will be assessed throughout the study period; suicidality will be obtained with the 
Columbia-Suicide Severity Rating Scale (C-SSRS). 
7   STATISTICAL ANALYSIS  
Data will be analyzed using IBM SPSS. We will report descriptive statistics and results from 
paired sample-tests to describe changes in primary and secondary outcomes from baseline to 14 
days post infusion. The following subsections describe the statistical procedures.  
8.1.   Descriptive Statistics 
All primary and secondary outcomes are continuous variables and descriptive statistics will be 
reported by mean and standard deviation.  
8.2.   Statistical Tests 
In the initial SAP, we proposed a mixed-effects regression to analyze the potential efficacy of the 
ketamine infusion. After study completion and careful consideration of the data collected, we decided 
to change the SAP to compare the mean differences of the primary and secondary outcomes between 
the baseline assessment and 14 days post infusion using paired sample t-tests.


Statistical Analysis Plan 
Page 6 of 6 
 
The normal distribution of the differences between the paired values will be tested using the Shapiro-
Wilk test and outliers will be reviewed using box plot diagrams. Estimated t-values, 95% confidence 
intervals, and p-values will be presented for each outcome variable.  
8   MISSING VALUES 
Missing values will be excluded from the statistical tests pairwise.  
9   REFERENCES 
Rodriguez, C.I., Kegeles, L.S., Levinson, A., Feng, T., Marcus, S.M., Vermes, D., …, & Simpson 
H.B.  (2013). Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: 
 
proof-of-concept. Neuropsychopharmacology, 38(12), 2475-2483.