Intranasal Ketamine In the Treatment of Pediatric Bipolar Disorder (IKBP)
This study is currently recruiting participants.
Verified July 2012 by Juvenile Bipolar Research Foundation
Sponsor:
Juvenile Bipolar Research Foundation
Information provided by (Responsible Party):
Juvenile Bipolar Research Foundation
ClinicalTrials.gov Identifier:
NCT01504659
First received: January 3, 2012
Last updated: July 9, 2012
Last verified: July 2012
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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:
|
|
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:
- Males and females aged 6-12;
- DSM-IV bipolar disorder (BPI, BPII, BP-NOS, BP-FOH);
- 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:
- Contraindication to the use of ketamine, including allergy and current use of medicine contraindicated with ketamine;
- Endocrine or neurological illness;
- 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;
- Previous history of glaucoma or acute globe injury
- Abnormal nasal physiology which would not allow for adequate medication delivery;
- Any change in medication type or dose within the past 30 days;
- Treatment with any MAOI's currently or within the past 3 months;
- Has had a course of ECT within the past 3 months;
- Has ever used PCP or ketamine;
- Meets DSM-IV criteria for Mental Retardation;
- Has ever had Repetitive Transcranial Magnetic Stimulation (rTMS), Vagal Nerve Stimulation (VNS) or Deep Brain Stimulation;
- Is currently hospitalized;
- Has known or suspected schizophrenia, even if currently stable or controlled with medications
- 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;
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01504659
Contacts
| Contact: Alissa B Bronsteen, BA | 609-240-2047 | abronsteen@comcast.net |
| Contact: Demitri Papolos, MD | 203-246-1939 | dpapolos@jbrf.org |
Locations
| United States, Connecticut | |
| Individual homes of subjects | Recruiting |
| Not Predetermined, Connecticut, United States | |
| Contact: Bronsteen abronsteen@comcast.net | |
| Principal Investigator: Demitri Papolos, MD | |
| United States, New Jersey | |
| Juvenile Bipolar Research Foundation | Not yet recruiting |
| Maplewood, New Jersey, United States, 07040 | |
| Contact: Alissa B Bronsteen, BA 609-240-2047 abronsteen@comcast.net | |
| Principal Investigator: Demitri Papolos, MD | |
| Sub-Investigator: Martin Teicher, MD, PhD | |
| Sub-Investigator: Steven Mattis, PhD | |
| Sub-Investigator: Patricia Murphy, PhD | |
| Sub-Investigator: Mark Frei, PhD | |
| Individual homes of subjects | Recruiting |
| Not Predetermined, New Jersey, United States | |
| Contact: Bronsteen abronsteen@comcast.net | |
| Principal Investigator: Demitri Papolos, MD | |
| United States, New York | |
| Individual homes of subjects | Recruiting |
| Not Predetermined, New York, United States | |
| Contact: Bronsteen abronsteen@comcast.net | |
| Principal Investigator: Demitri Papolos, MD | |
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: | July 9, 2012 |
| 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 Affective Disorders, Psychotic Mood Disorders Mental Disorders Ketamine Anesthetics, Dissociative Anesthetics, Intravenous Anesthetics, General Anesthetics Central Nervous System Depressants Physiological Effects of Drugs |
Pharmacologic Actions Central Nervous System Agents Therapeutic Uses Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Analgesics Sensory System Agents Peripheral Nervous System Agents |
ClinicalTrials.gov processed this record on May 23, 2013