Bipolar DisorderPhase 2/3IKBPNCT01504659
Intranasal Ketamine In the Treatment of Pediatric Bipolar Disorder
A Phase 2/3 study testing Ketamine hydrochloride injection and Flat tonic water (e.g., Canada Dry Tonic Water) in people with Bipolar Disorder, run by Juvenile Bipolar Research Foundation at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 12 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Ketamine hydrochloride injection and Flat tonic water (e.g., Canada Dry Tonic Water)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 4 sitesUnited States
- Study dates
- Jul 2012to Nov 2016
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Juvenile Bipolar Research Foundation
Maplewood, New Jersey, 07040
Individual homes of subjects
Not Predetermined, Connecticut
Individual homes of subjects
Not Predetermined, New Jersey
Individual homes of subjects
Not Predetermined, New York
About this study
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
- Being tested
- Ketamine hydrochloride injection, Flat tonic water (e.g., Canada Dry Tonic Water)
- Keywords
- bipolar disorder, treatment resistance, depression, ketamine, intranasal, child
- Medical subject headings
- Bipolar Disorder, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketamine hydrochloride injectionDrug
Also called Ketalar NDA 016812, Ketamine Hydrochloride Injection, Abbot Hospital, 074549, Ketamine Hdyrochloride Injection, Bioniche, 076092, Ketamine Hydrochloride Injection, Bedford, 074524
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| Bipolar-Ketalar | Active comparator | Children with a diagnosis of BP-I, BP-II or BP-NOS will receive 4 administrations of intranasal ketalar Receives: 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 Receives: Drug: Flat tonic water (e.g., Canada Dry Tonic Water) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Young Mania Rating Scale
Measured: Change from baseline at 8 days
Young Mania Rating Scale
Measured: Change from baseline at 11 days
Young Mania Rating Scale
Measured: Change from baseline at 14 days
Young Mania Rating Scale
Measured: Change from baseline at 17 days
Overt Aggression Scale
Measured: Change from baseline at day 8
Overt Aggression Scale
Measured: Change from baseline at day 11
Overt Aggression Scale
Measured: Change from baseline at day 14
Overt Aggression Scale
Measured: Change from baseline at day 17
Yale Brown Obsessive Compulsive Scale
Measured: Change from baseline at Day 18, aggressive and obsessive questions
Secondary outcomes (9)
Wechsler Intelligence Scale for Children-IV
Measured: Change from baseline at day 18
Peripheral Thermal Challenge
Measured: Change from baseline on days 6, 7, 15 and 16
body temperature
A proprietary ambulatory monitor will measure skin and tympanic temperature using conventional thermistors and IR sensors
Measured: Change from baseline over 16 hours spanning days 6-7 and 15-16.
Triaxial acceleration
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.
Measured: Change from baseline over 16 hours spanning days 6-7 and 15-16.
SpO2
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.
Measured: Change from baseline over 16 hours spanning days 6-7 and 15-16.
Galvanic skin response
A proprietary ambulatory monitor will measure galvanic skin response obtained with two conventional electrodes.
Measured: Change from baseline over 16 hours spanning days 6-7 and 15-16.
Delis-Kaplin Executive Function System
Measured: Change from baseline on day 18
Conner's Continuous Performance Test
Measured: Change from baseline on day 18
SCARED
Measured: change from baseline at day 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2012 (estimated)
- Study startJul 2012
- Primary completionNov 2016
- Study completionNov 2016
Why it stopped: Administrative issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Juvenile Bipolar Research Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Demitri Papolos, MD, Principal investigator, Juvenile Bipolar Research Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01504659
- Sponsor's protocol ID
- JBRF001
- Acronym
- IKBP
- Status last verified
- Mar 2017
- First submitted
- 3 Jan 2012
- Last updated
- 16 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intranasal Ketamine In the Treatment of Pediatric Bipolar Disorder
- ClinicalTrials.gov ID
- NCT01504659
- Acronym / sponsor ID
- IKBP / JBRF001
- Conditions
- Bipolar Disorder
- Keywords
- bipolar disorder, treatment resistance, depression, ketamine, intranasal, child
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Administrative issues
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Juvenile Bipolar Research FoundationUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 5 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bipolar-Ketalar | Active comparator | Drug: Ketamine hydrochloride injectionChildren with a diagnosis of BP-I, BP-II or BP-NOS will receive 4 administrations of intranasal ketalar |
| Bipolar-Placebo | Placebo comparator | Drug: Flat tonic water (e.g., Canada Dry Tonic Water)Children with a diagnosis of BP-I, BP-II or BP-NOS will receive 4 administrations of placebo |
Who may qualify
- Ages
- 6 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (15 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketamine hydrochloride injectionAlso: Ketalar NDA 016812, Ketamine Hydrochloride Injection, Abbot Hospital, 074549, Ketamine Hdyrochloride Injection, Bioniche, 076092, Ketamine Hydrochloride Injection, Bedford, 074524Separate 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. | Drug | Bipolar-Ketalar |
| 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. | Drug | Bipolar-Placebo |
Primary outcome
Young Mania Rating Scale
Time frame: Change from baseline at 8 days
Young Mania Rating Scale
Time frame: Change from baseline at 11 days
Young Mania Rating Scale
Time frame: Change from baseline at 14 days
Young Mania Rating Scale
Time frame: Change from baseline at 17 days
Overt Aggression Scale
Time frame: Change from baseline at day 8
Overt Aggression Scale
Time frame: Change from baseline at day 11
Overt Aggression Scale
Time frame: Change from baseline at day 14
Overt Aggression Scale
Time frame: Change from baseline at day 17
Yale Brown Obsessive Compulsive Scale
Time frame: Change from baseline at Day 18, aggressive and obsessive questions
9 secondary outcomes
Wechsler Intelligence Scale for Children-IV
Time frame: Change from baseline at day 18
Peripheral Thermal Challenge
Time frame: Change from baseline on days 6, 7, 15 and 16
body temperature
Time frame: Change from baseline over 16 hours spanning days 6-7 and 15-16.
Triaxial acceleration
Time frame: Change from baseline over 16 hours spanning days 6-7 and 15-16.
SpO2
Time frame: Change from baseline over 16 hours spanning days 6-7 and 15-16.
Galvanic skin response
Time frame: Change from baseline over 16 hours spanning days 6-7 and 15-16.
Delis-Kaplin Executive Function System
Time frame: Change from baseline on day 18
Conner's Continuous Performance Test
Time frame: Change from baseline on day 18
SCARED
Time frame: change from baseline at day 18
Results and safety
The study was stopped early (reason given: Administrative issues). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2017.
- Juvenile Bipolar Research FoundationLink provided by the sponsor.
- Fear of harm, a possible phenotype of pediatric bipolar disorderLink provided by the sponsor.
- Diagnostic Assessment Program for Juvenile Bipolar DisorderLink provided by the sponsor.
- A strategy for identifying phenotypic subtypesLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Demitri Papolos, MD principal investigator
Juvenile Bipolar Research Foundation
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Ketamine hydrochloride injection and Flat tonic water (e.g., Canada Dry Tonic Water) in people with Bipolar Disorder, run by Juvenile Bipolar Research Foundation at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Administrative issues). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Young Mania Rating Scale (time frame: Change from baseline at 8 days). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2017.