Intranasal Ketamine In the Treatment of Pediatric Bipolar Disorder (IKBP)

This study has suspended participant recruitment.
Sponsor:
Information provided by (Responsible Party):
Juvenile Bipolar Research Foundation
ClinicalTrials.gov Identifier:
NCT01504659
First received: January 3, 2012
Last updated: November 20, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Bipolar Disorder
Drug: Ketamine hydrochloride injection
Drug: Flat tonic water (e.g., Canada Dry Tonic Water)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intranasal Ketamine In the Treatment of Pediatric Bipolar Disorder

Resource links provided by NLM:


Further study details as provided by Juvenile Bipolar Research Foundation:

Primary Outcome Measures:
  • Young Mania Rating Scale [ Time Frame: Change from baseline at 8 days ] [ Designated as safety issue: No ]
  • Young Mania Rating Scale [ Time Frame: Change from baseline at 11 days ] [ Designated as safety issue: No ]
  • Young Mania Rating Scale [ Time Frame: Change from baseline at 14 days ] [ Designated as safety issue: No ]
  • Young Mania Rating Scale [ Time Frame: Change from baseline at 17 days ] [ Designated as safety issue: No ]
  • Overt Aggression Scale [ Time Frame: Change from baseline at day 8 ] [ Designated as safety issue: No ]
  • Overt Aggression Scale [ Time Frame: Change from baseline at day 11 ] [ Designated as safety issue: No ]
  • Overt Aggression Scale [ Time Frame: Change from baseline at day 14 ] [ Designated as safety issue: No ]
  • Overt Aggression Scale [ Time Frame: Change from baseline at day 17 ] [ Designated as safety issue: No ]
  • Yale Brown Obsessive Compulsive Scale [ Time Frame: Change from baseline at Day 18, aggressive and obsessive questions ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Wechsler Intelligence Scale for Children-IV [ Time Frame: Change from baseline at day 18 ] [ Designated as safety issue: No ]
  • Peripheral Thermal Challenge [ Time Frame: Change from baseline on days 6, 7, 15 and 16 ] [ Designated as safety issue: No ]
  • body temperature [ Time Frame: Change from baseline over 16 hours spanning days 6-7 and 15-16. ] [ Designated as safety issue: No ]
    A proprietary ambulatory monitor will measure skin and tympanic temperature using conventional thermistors and IR sensors

  • Triaxial acceleration [ Time Frame: Change from baseline over 16 hours spanning days 6-7 and 15-16. ] [ Designated as safety issue: No ]
    A proprietary ambulatory monitor will measure triaxial acceleration from the forehead using a commercially-available sensor that also provides a plethysmograph signal from which heart rate can be derived.

  • SpO2 [ Time Frame: Change from baseline over 16 hours spanning days 6-7 and 15-16. ] [ Designated as safety issue: No ]
    A proprietary ambulatory monitor will measure triaxial acceleration from the forehead using a commercially-available sensor that also provides a plethysmograph signal from which heart rate can be derived.

  • Galvanic skin response [ Time Frame: Change from baseline over 16 hours spanning days 6-7 and 15-16. ] [ Designated as safety issue: No ]
    A proprietary ambulatory monitor will measure galvanic skin response obtained with two conventional electrodes.

  • Delis-Kaplin Executive Function System [ Time Frame: Change from baseline on day 18 ] [ Designated as safety issue: No ]
  • Conner's Continuous Performance Test [ Time Frame: Change from baseline on day 18 ] [ Designated as safety issue: No ]
  • SCARED [ Time Frame: change from baseline at day 18 ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: July 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Bipolar-Ketalar
Children with a diagnosis of BP-I, BP-II or BP-NOS will receive 4 administrations of intranasal ketalar
Drug: Ketamine hydrochloride injection
Separate dosing regimens will be applied depending on the weight of the child. Group A with minimum-maximum weight of 20 kg-40 kg will receive a fixed initial dose of 10 mg ketamine(0.25-0.5mg/kg)and will not exceed a maximum dose of 40 mg ketamine. Group B with minimum - maximum weight of 40.01kg-100kg will get a fixed initial dose of 20 mg ketamine(0.20-0.5mg/kg) and will not exceed a maximum dose of 120mg. ketamine. There will be 4 administrations of the drug at three day intervals. Titration upward will depend upon degree of side effects, improvement from baseline on primary measures, subjective opinion. Doses will be held constant as long as a therapuetic response, as measure of 80% improvement on YBOCS and YMRS, is reached.
Other Names:
  • Ketalar NDA 016812
  • Ketamine Hydrochloride Injection, Abbot Hospital, 074549
  • Ketamine Hdyrochloride Injection, Bioniche, 076092
  • Ketamine Hydrochloride Injection, Bedford, 074524
  • Calypsol
  • Ketalin
  • Ketamax
  • Ketanest
  • Ketava
  • Ketmin
  • Ketolar
  • Petar
  • Soon-Soon
Placebo Comparator: Bipolar-Placebo
Children with a diagnosis of BP-I, BP-II or BP-NOS will receive 4 administrations of placebo
Drug: Flat tonic water (e.g., Canada Dry Tonic Water)
Separate dosing regimens will be applied depending on the weight of the child. Group A with minimum-maximum weight of 20 kg-40 kg will receive a fixed initial dose of 0.1cc placebo and not exceed a maximum dose of 0.4cc placebo. Group B with minimum - maximum weight of 40.01kg-100kg will get a fixed initial dose of 0.2cc placebo and will not exceed a maximum dose of 1.2cc. placebo. There will be 4 administrations of the placebo at three day intervals. Titration upward will depend upon degree of side effects, improvement from baseline on primary measures, and subjective opinion. Doses will be held constant as long as a therapuetic response, as a measure of 80% improvement on YBOCS and YMRS, is reached.

  Eligibility

Ages Eligible for Study:   6 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01504659

Locations
United States, Connecticut
Individual homes of subjects
Not Predetermined, Connecticut, United States
United States, New Jersey
Juvenile Bipolar Research Foundation
Maplewood, New Jersey, United States, 07040
Individual homes of subjects
Not Predetermined, New Jersey, United States
United States, New York
Individual homes of subjects
Not Predetermined, New York, United States
Sponsors and Collaborators
Juvenile Bipolar Research Foundation
Investigators
Principal Investigator: Demitri Papolos, MD Juvenile Bipolar Research Foundation
  More Information

Additional Information:
No publications provided

Responsible Party: Juvenile Bipolar Research Foundation
ClinicalTrials.gov Identifier: NCT01504659     History of Changes
Other Study ID Numbers: JBRF001
Study First Received: January 3, 2012
Last Updated: November 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Juvenile Bipolar Research Foundation:
bipolar disorder
treatment resistance
depression
ketamine
intranasal
child

Additional relevant MeSH terms:
Bipolar Disorder
Disease
Affective Disorders, Psychotic
Mental Disorders
Mood Disorders
Pathologic Processes
Ketamine
Analgesics
Anesthetics
Anesthetics, Dissociative
Anesthetics, General
Anesthetics, Intravenous
Central Nervous System Agents
Central Nervous System Depressants
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014