NCT01504659

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.

Trial Health

57
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jul 2012

Typical duration for phase_2

Geographic Reach
1 country

4 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 3, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 5, 2012

Completed
6 months until next milestone

Study Start

First participant enrolled

July 1, 2012

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2016

Completed
Last Updated

March 16, 2017

Status Verified

March 1, 2017

Enrollment Period

4.3 years

First QC Date

January 3, 2012

Last Update Submit

March 14, 2017

Conditions

Bipolar Disorder

Keywords

bipolar disordertreatment resistancedepressionketamineintranasalchild

Outcome Measures

Primary Outcomes (9)

  • Young Mania Rating Scale

    Change from baseline at 8 days

  • Young Mania Rating Scale

    Change from baseline at 11 days

  • Young Mania Rating Scale

    Change from baseline at 14 days

  • Young Mania Rating Scale

    Change from baseline at 17 days

  • Overt Aggression Scale

    Change from baseline at day 8

  • Overt Aggression Scale

    Change from baseline at day 11

  • Overt Aggression Scale

    Change from baseline at day 14

  • Overt Aggression Scale

    Change from baseline at day 17

  • Yale Brown Obsessive Compulsive Scale

    Change from baseline at Day 18, aggressive and obsessive questions

Secondary Outcomes (9)

  • Wechsler Intelligence Scale for Children-IV

    Change from baseline at day 18

  • Peripheral Thermal Challenge

    Change from baseline on days 6, 7, 15 and 16

  • body temperature

    Change from baseline over 16 hours spanning days 6-7 and 15-16.

  • Triaxial acceleration

    Change from baseline over 16 hours spanning days 6-7 and 15-16.

  • SpO2

    Change from baseline over 16 hours spanning days 6-7 and 15-16.

  • +4 more secondary outcomes

Study Arms (2)

Bipolar-Ketalar

ACTIVE COMPARATOR

Children with a diagnosis of BP-I, BP-II or BP-NOS will receive 4 administrations of intranasal ketalar

Drug: Ketamine hydrochloride injection

Bipolar-Placebo

PLACEBO COMPARATOR

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)

Interventions

Ketamine hydrochloride injectionDRUG

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.

Also known as: 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
Bipolar-Ketalar
Flat tonic water (e.g., Canada Dry Tonic Water)DRUG

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.

Bipolar-Placebo

Eligibility Criteria

Age6 Years - 12 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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.

You may not qualify if:

  • 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;

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Individual homes of subjects

Not Predetermined, Connecticut, United States

Location

Juvenile Bipolar Research Foundation

Maplewood, New Jersey, 07040, United States

Location

Individual homes of subjects

Not Predetermined, New Jersey, United States

Location

Individual homes of subjects

Not Predetermined, New York, United States

Location

Related Links

MeSH Terms

Conditions

Bipolar DisorderDepression

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Bipolar and Related DisordersMood DisordersMental DisordersBehavioral SymptomsBehavior

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Study Officials

  • Demitri Papolos, MD

    Juvenile Bipolar Research Foundation

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 3, 2012

First Posted

January 5, 2012

Study Start

July 1, 2012

Primary Completion

November 1, 2016

Study Completion

November 1, 2016

Last Updated

March 16, 2017

Record last verified: 2017-03

Locations

US(4)