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

Obsessive-Compulsive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02422290
• Other study ID #: #7023
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2015
• Est. completion date: July 31, 2020

Study information

• Verified date: August 2020
• Source: New York State Psychiatric Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

See Brief Summary for description.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: July 31, 2020
• Est. primary completion date: February 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 22 Years

Eligibility

Inclusion Criteria:

1. Participant must be 14-22 years of age at the time of consent (post-pubertal)

2. Participant and a parent/guardian must be able to read and understand English

3. Participant must be physically healthy and weigh at least 25kg. If female, must not be pregnant.

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.

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..

6. 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.

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.

8. 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.

Exclusion Criteria:

1. Family history of psychosis or substance abuse/dependence.

2. History of violence

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.

4. Severely depressed patients with the Children's Depression Rating Scale (CDRS) = 60 or judged clinically to be at risk of suicide.

5. Current diagnosis of an eating disorder.

6. Current or past history of PTSD or significant trauma.

7. Current or past diagnosis of substance abuse/dependence.

8. 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.

9. 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.

10. Documented history of hypersensitivity or intolerance to ketamine.

11. 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.

12. 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.

13. 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.

14. Positive urine screen for illicit drugs

15. Inability of participant or parent/guardian to read or understand English.

16. Documented history of adverse reaction to anesthesia.

Related Conditions & MeSH terms

• Disease
• Obsessive-Compulsive Disorder

Intervention

Drug:
• Ketamine
Single infusion of IV Ketamine, 0.5mg/kg

Locations

Country	Name	City	State
United States	New York State Psychiatric Institute/Columbia University	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York State Psychiatric Institute	New York Presbyterian Hospital

Country where clinical trial is conducted

United States, 

References & Publications (22)

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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. 2007 Jan 30;31(1):46-52. Epub 2006 Jul 20. — View Citation

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. — View Citation

Bloch MH, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry. 2006 Jul;11(7):622-32. Epub 2006 Apr 4. Review. Erratum in: Mol Psychiatry. 2006 Aug;11(8):795. — View Citation

Chakrabarty K, Bhattacharyya S, Christopher R, Khanna S. Glutamatergic dysfunction in OCD. Neuropsychopharmacology. 2005 Sep;30(9):1735-40. — View Citation

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). 2003 May;167(2):219-20. Epub 2003 Mar 26. — View Citation

Correll CU. Assessing and maximizing the safety and tolerability of antipsychotics used in the treatment of children and adolescents. J Clin Psychiatry. 2008;69 Suppl 4:26-36. Review. — View Citation

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. Review. — View Citation

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. Epub 2007 Apr 16. — View Citation

Graybiel AM, Rauch SL. Toward a neurobiology of obsessive-compulsive disorder. Neuron. 2000 Nov;28(2):343-7. Review. — View Citation

Hezel DM, Beattie K, Stewart SE. Memantine as an augmenting agent for severe pediatric OCD. Am J Psychiatry. 2009 Feb;166(2):237. doi: 10.1176/appi.ajp.2008.08091427. — View Citation

Kararmaz A, Kaya S, Turhanoglu S, Ozyilmaz MA. Oral ketamine premedication can prevent emergence agitation in children after desflurane anaesthesia. Paediatr Anaesth. 2004 Jun;14(6):477-82. — View Citation

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. — View Citation

Papolos DF, Teicher MH, Faedda GL, Murphy P, Mattis S. Clinical experience using intranasal ketamine in the treatment of pediatric bipolar disorder/fear of harm phenotype. J Affect Disord. 2013 May;147(1-3):431-6. doi: 10.1016/j.jad.2012.08.040. Epub 2012 Nov 30. — View Citation

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. — View Citation

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. Epub 2006 Feb 21. — View Citation

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. 2010 Sep;71(9):1247-9. doi: 10.4088/JCP.09l05805blu. — View Citation

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. — View Citation

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. — View Citation

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.

Stewart SE, Jenike EA, Hezel DM, Stack DE, Dodman NH, Shuster L, Jenike MA. A single-blinded case-control study of memantine in severe obsessive-compulsive disorder. J Clin Psychopharmacol. 2010 Feb;30(1):34-9. doi: 10.1097/JCP.0b013e3181c856de. — View Citation

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. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	OCD Visual Analogue Scale (OCD-VAS)	The OCD-VAS is a one-item unipolar scale to assess OCD symptoms over a rapid time frame ("No obsessions" to "Constant obsessions"). The scale ranges from 0-10 with higher scores indicating higher presence of obsessions.	Screening, Baseline, Day 1-14, 3-Month; Baseline and Day 14 pre-specified to be reported
Secondary	Yale-Brown Obsessive Compulsive Challenge Scale (Y-BOCCS)	The Y-BOCCS is self-report scale which assesses OCD symptoms on a 5-point likert scale ("None" to "Extreme"). It consists of 10 items which are summed up to derive the total Y-BOCCS score. The total score ranges from 0-40 with higher scores indicating higher prevalence of OCD symptoms.	Screening, Baseline, Day 1-14, 3-Month; Baseline and Day 14 pre-specified to be reported