Intranasal Ketamine In the Treatment of Pediatric Bipolar Disorder

NCT ID: NCT01504659

Last Updated: 2017-03-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2016-11-30

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.

Conditions

Bipolar Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Bipolar-Ketalar

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

Group Type: ACTIVE_COMPARATOR

Ketamine hydrochloride injection

Intervention Type: 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 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.

Bipolar-Placebo

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

Group Type: PLACEBO_COMPARATOR

Flat tonic water (e.g., Canada Dry Tonic Water)

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention 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

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Juvenile Bipolar Research Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Demitri Papolos, MD

Role: PRINCIPAL_INVESTIGATOR

Juvenile Bipolar Research Foundation

Locations

Individual homes of subjects

Not Predetermined, Connecticut, United States

Juvenile Bipolar Research Foundation

Maplewood, New Jersey, United States

Individual homes of subjects

Not Predetermined, New Jersey, United States

Individual homes of subjects

Not Predetermined, New York, United States

Countries

United States

Related Links

http://www.jbrf.org/

Juvenile Bipolar Research Foundation

http://www.jbrf.org/librarydocs/correctedproof-7-23-09.pdf

Fear of harm, a possible phenotype of pediatric bipolar disorder

http://www.jbrf.org/cpp/index.html

Diagnostic Assessment Program for Juvenile Bipolar Disorder

http://www.jbrf.org/librarydocs/JADPhenotypeArticle.pdf

A strategy for identifying phenotypic subtypes

Other Identifiers

JBRF001

Identifier Type: -

Identifier Source: org_study_id