Clinical trial NCT01504659: Intranasal Ketamine In the Treatment of Pediatric Bipolar Disorder
Official title: Intranasal Ketamine In the Treatment of Pediatric Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Bipolar Disorder
Keywords: bipolar disorder
treatment resistance
depression
ketamine
intranasal
child
Lead sponsor: Juvenile Bipolar Research Foundation
Sponsor class: OTHER
First posted: 2012-01-05
Enrollment: 5
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators plan to evaluate the efficacy and safety of intranasal Ketalar (ketamine hydrochloride) in the treatment of primary symptom manifestations of pediatric bipolar disorder; Fear of Harm (FOH) phenotype. This phenotype represents those children who are most resistant to traditional treatments and suffer repeated hospitalizations. Primary symptoms include fearfulness, aggression secondary to threat, mood and/or arousal instability, and psychosis. In addition to evaluation of efficacy and safety, the investigators will also analyze whether therapeutic response depends upon the degree to which the subject fits the FOH phenotype.


Eligibility criteria: Inclusion Criteria:

1. Males and females aged 6-12;
2. DSM-IV bipolar disorder (BPI, BPII, BP-NOS, BP-FOH);
3. Treatment resistant - as defined by failure to adequately respond to at least 2 different classes of medications such as mood stabilizers and antipsychotic agent.

Exclusion Criteria:

1. Contraindication to the use of ketamine, including allergy and current use of medicine contraindicated with ketamine;
2. Endocrine or neurological illness;
3. Previous history of closed head injury, current head injury associated with possible intracranial hypertension, central nervous system masses, abnormalities, or hydrocephalus, ever had loss of consciousness;
4. Previous history of glaucoma or acute globe injury
5. Abnormal nasal physiology which would not allow for adequate medication delivery;
6. Any change in medication type or dose within the past 30 days;
7. Treatment with any MAOI's currently or within the past 3 months;
8. Has had a course of ECT within the past 3 months;
9. Has ever used PCP or ketamine;
10. Meets DSM-IV criteria for Mental Retardation;
11. Has ever had Repetitive Transcranial Magnetic Stimulation (rTMS), Vagal Nerve Stimulation (VNS) or Deep Brain Stimulation;
12. Is currently hospitalized;
13. Has known or suspected schizophrenia, even if currently stable or controlled with medications
14. Is acutely suicidal or homicidal (i.e., in imminent danger with plan, urges and intent to harm oneself or others) including any serious attempts/those requiring hospitalization in the past 12 months or at the PI's discretion;
15. The presence of any abnormal laboratory findings or serious medical disorder or condition including: clinically significant organ system dysfunction; significant endocrine disease, including diabetes mellitus; hypothyroidism; cardiovascular disease (myocardial ischemia, heart failure, arrhythmias); coagulopathy; significant anemia; significant acute infection; glaucoma; dehydration; epilepsy; any intra-abdominal or intrathoracic surgery or limb amputation within the prior 6 months; any diagnosed cardiac condition causing documented hemodynamic compromise or dysfunction of the SA or AV node; any diagnosed respiratory condition causing documented or clinically recognized hypoxia (e.g., chronic obstructive or restrictive pulmonary disease); body weight approximately \< 80% or \> 120% ideal body weight; or any medical condition known to interfere with cognitive performance; medication-related exclusions include narcotic therapy, chronic acetaminophen use, acute sedative hypnotic withdrawal, corticosteroid or spironolactone therapy, regularly dosed narcotics or any other sedative therapy or medication that interferes with SA or AV node function or could be considered contraindicated with the sedative properties of ketamine.

Primary outcomes:
measure: Young Mania Rating Scale
timeFrame: Change from baseline at 8 days
measure: Young Mania Rating Scale
timeFrame: Change from baseline at 11 days
measure: Young Mania Rating Scale
timeFrame: Change from baseline at 14 days
measure: Young Mania Rating Scale
timeFrame: Change from baseline at 17 days
measure: Overt Aggression Scale
timeFrame: Change from baseline at day 8
measure: Overt Aggression Scale
timeFrame: Change from baseline at day 11
measure: Overt Aggression Scale
timeFrame: Change from baseline at day 14
measure: Overt Aggression Scale
timeFrame: Change from baseline at day 17
measure: Yale Brown Obsessive Compulsive Scale
timeFrame: Change from baseline at Day 18, aggressive and obsessive questions
Secondary outcomes:
measure: Wechsler Intelligence Scale for Children-IV
timeFrame: Change from baseline at day 18
measure: Peripheral Thermal Challenge
timeFrame: Change from baseline on days 6, 7, 15 and 16
measure: body temperature
timeFrame: Change from baseline over 16 hours spanning days 6-7 and 15-16.
measure: Triaxial acceleration
timeFrame: Change from baseline over 16 hours spanning days 6-7 and 15-16.
measure: SpO2
timeFrame: Change from baseline over 16 hours spanning days 6-7 and 15-16.
measure: Galvanic skin response
timeFrame: Change from baseline over 16 hours spanning days 6-7 and 15-16.
measure: Delis-Kaplin Executive Function System
timeFrame: Change from baseline on day 18
measure: Conner's Continuous Performance Test
timeFrame: Change from baseline on day 18
measure: SCARED
timeFrame: change from baseline at day 18
Other outcomes:
Locations:
city: Not Predetermined
country: United States
facility: Individual homes of subjects
state: Connecticut
city: Maplewood
country: United States
facility: Juvenile Bipolar Research Foundation
state: New Jersey
city: Not Predetermined
country: United States
facility: Individual homes of subjects
state: New Jersey
city: Not Predetermined
country: United States
facility: Individual homes of subjects
state: New York
Study officials:
affiliation: Juvenile Bipolar Research Foundation
name: Demitri Papolos, MD
role: PRINCIPAL_INVESTIGATOR
References: