Ketamine Treatment for Pediatric-Refractory Obsessive-Compulsive Disorder (OCD)

NCT02422290 | Completed Phase 1 Results

• 1 other identifier: #7023
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Obsessive-Compulsive Disorder

Keywords

Obsessive Compulsive Disorder; Ketamine; Glutamate; OCD treatment; OCD medication

Outcome Measures

Primary Outcomes (2)

• Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)

  The CY-BOCS 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 CY-BOCS consists of 10 items which are summed up to derive the total CY-BOCS score. The total score ranges from 0-40 with higher scores indicating greater severity of OCD symptoms.

  Screening, Baseline, Day 7, Day 17, 3-Month; Baseline and Day 14 pre-specified to be reported

• Clinical Global Impressions - Severity Scale (CGI-S)

  The CGI-S is a clinician rated 7-point rating scale for the severity of a participant's illness relative to the clinician's experience of working with this particular population. The score ranges from 1-7 with higher scores indicating greater illness severity.

  Screening, Baseline, Day 7, Day 17, 3-Month; Baseline and Day 14 pre-specified to be reported

Secondary Outcomes (2)

• OCD Visual Analogue Scale (OCD-VAS)

  Screening, Baseline, Day 1-14, 3-Month; Baseline and Day 14 pre-specified to be reported

• Yale-Brown Obsessive Compulsive Challenge Scale (Y-BOCCS)

  Screening, Baseline, Day 1-14, 3-Month; Baseline and Day 14 pre-specified to be reported

Study Arms (1)

Adolescents and young adults with OCD

EXPERIMENTAL

All participants will be receive the intravenous ketamine infusion.

Drug: Ketamine

Interventions

Ketamine DRUG

Single infusion of IV Ketamine, 0.5mg/kg

Also known as: Ketalar

Adolescents and young adults with OCD

Eligibility Criteria

• Age: 14 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participant must be 14-22 years of age at the time of consent (post-pubertal)
• Participant and a parent/guardian must be able to read and understand English
• Participant must be physically healthy and weigh at least 25kg. If female, must not be pregnant.
• 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.
• 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..
• Participant must have tried and failed at least one adequate trial of SRI medications or clomipramine and a course of CBT unless the participant is unable to access or tolerate CBT treatment.
• In order to meet criteria for having had at least one adequate trial of SRI medication, participants must have been on a stable and minimal adequate dose of at least one SRI 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 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.
• 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.
• 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.
• For participants younger than 18, written informed assent by the participant and consent by the parent. For participants 19 and older, written consent by the participant and permission for legal guardian/parent to provide information.

You may not qualify if:

• Family history of psychosis or substance abuse/dependence.
• History of violence
• 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.
• Severely depressed patients with the Children's Depression Rating Scale (CDRS) ≥ 60 or judged clinically to be at risk of suicide.
• Current diagnosis of an eating disorder.
• Current or past history of PTSD or significant trauma.
• Current or past diagnosis of substance abuse/dependence.
• 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.
• 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.
• Documented history of hypersensitivity or intolerance to ketamine.
• 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.
• 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, or hydrocephalus.
• Concurrent use of any medications that might increase the risk of participation. This would include: St. John's Wort, Tramadol or atracurium, due to potential adverse drug-drug interactions.
• Positive urine screen for illicit drugs
• Inability of participant or parent/guardian to read or understand English.

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• New York Presbyterian Hospital: collaborator

Study Sites (1)

New York State Psychiatric Institute/Columbia University

New York, New York, 10032, United States

Location

Related Publications (23)

• Rauch SL, Wedig MM, Wright CI, Martis B, McMullin KG, Shin LM, Cannistraro PA, Wilhelm S. Functional magnetic resonance imaging study of regional brain activation during implicit sequence learning in obsessive-compulsive disorder. Biol Psychiatry. 2007 Feb 1;61(3):330-6. doi: 10.1016/j.biopsych.2005.12.012. Epub 2006 Feb 21.

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• Graybiel AM, Rauch SL. Toward a neurobiology of obsessive-compulsive disorder. Neuron. 2000 Nov;28(2):343-7. doi: 10.1016/s0896-6273(00)00113-6. No abstract available.

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• Chakrabarty K, Bhattacharyya S, Christopher R, Khanna S. Glutamatergic dysfunction in OCD. Neuropsychopharmacology. 2005 Sep;30(9):1735-40. doi: 10.1038/sj.npp.1300733.

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• 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. 2000 Sep;39(9):1096-103. doi: 10.1097/00004583-200009000-00008.

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  PMID: 15153210 BACKGROUND

• Dahmani S, Michelet D, Abback PS, Wood C, Brasher C, Nivoche Y, Mantz J. Ketamine for perioperative pain management in children: a meta-analysis of published studies. Paediatr Anaesth. 2011 Jun;21(6):636-52. doi: 10.1111/j.1460-9592.2011.03566.x. Epub 2011 Mar 29.

  PMID: 21447047 BACKGROUND

• Finkel JC, Pestieau SR, Quezado ZM. Ketamine as an adjuvant for treatment of cancer pain in children and adolescents. J Pain. 2007 Jun;8(6):515-21. doi: 10.1016/j.jpain.2007.02.429. Epub 2007 Apr 16.

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• Rodriguez CI, Kegeles LS, Levinson A, Feng T, Marcus SM, Vermes D, Flood P, Simpson HB. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology. 2013 Nov;38(12):2475-83. doi: 10.1038/npp.2013.150. Epub 2013 Jun 19.

  PMID: 23783065 BACKGROUND

• Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9.

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• Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64. doi: 10.1001/archpsyc.63.8.856.

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• Marcus RJ, Victoria BA, Rushman SC, Thompson JP. Comparison of ketamine and morphine for analgesia after tonsillectomy in children. Br J Anaesth. 2000 Jun;84(6):739-42. doi: 10.1093/oxfordjournals.bja.a013585.

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• Pediatric OCD Treatment Study (POTS) Team. 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. 2004 Oct 27;292(16):1969-76. doi: 10.1001/jama.292.16.1969.

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• Ishimuro HS, Yanes-Lukin PK, Goldberg PH, Simpson HB, Rynn MA. Ketamine Treatment for Pediatric Refractory Obsessive: Five Open Label Cases. J Child Adolesc Psychopharmacol. 2025 Apr;35(3):167-170. doi: 10.1089/cap.2024.0127. Epub 2025 Feb 3.

  PMID: 39899368 DERIVED

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Pablo H. Goldberg, MD
• Organization: New York State Psychiatric Institute

Pablo.Goldberg@nyspi.columbia.edu

646-774-6318

Study Officials

• Pablo Goldberg, M.D.

  Columbia University/NYSPI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Psychiatrist

Study Record Dates

• First Submitted: April 13, 2015
• First Posted: April 21, 2015
• Study Start: March 1, 2015
• Primary Completion: February 21, 2018
• Study Completion: July 31, 2020
• Last Updated: August 17, 2020
• Results First Posted: August 17, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)