Psychoses, Substance-InducedPhase 4NCT00205712
Prevention of N-methyl-D-aspartate (NMDA) Antagonist-induced Psychosis in Kids
A Phase 4 study testing Ketamine and Dexmedetomidine in people with Psychoses, Substance-Induced, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Ketamine, an FDA approved anesthetic agent, is becoming the sedative/analgesic of choice for emergency sedation in children because it causes deep sedation with minimal respiratory depression in comparison to other available agents. Read more about this study
- Who is it for?
- Ages 7 to 17 years
- Conditions the study is for
- Psychoses, Substance-Induced
- What is being tested?
- Ketamine and Dexmedetomidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2003to Oct 2007
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 7 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients presenting to St. Louis Children's Hospital's Emergency Department who require reduction of an acute forearm fracture will be recruited for enrollment if they satisfy the following:
- Age 7-17 years, inclusive;
- Are psychiatrically healthy (i.e. have never been under the care of a psychiatrist or taken psychiatrically active medications);
- Meet American Society of Anesthesiologist (ASA) Class I and II criteria (I=healthy, II=chronic disease under good control);
- Have had no prior fracture reduction or ketamine administration;
- Present for care when research assistants are present (Monday-Friday, 09:00-23:00); and
- Have a home telephone or ready means of establishing telephone contact.
- All subjects and their parent/guardian will give Washington University Human Studies Committee approved written informed assent and consent prior to participation.
Who cannot join
- Solid food intake 2 hours or less before procedure;
- Compromised cardiorespiratory function; central nervous system, hepatic, or renal abnormality;
- History of psychosis in patient or first degree relative;
- Currently taking medications that stimulate or depress mental function, e.g. methylphenidate for attention deficit hyperactivity disorder or drugs of abuse;
- History of allergy or adverse reaction to alpha-2 adrenoreceptor agonist drugs, e.g. clonidine.
- These exclusion criteria relate to contraindications for use of the agents employed in the study. Criteria 1, 2, 3 and 4 are current routine practice for ketamine sedations.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine, Psychiatry Dept.
St Louis, Missouri, 63110
About this study
Official title: Prevention of NMDA Antagonist-induced Psychosis and Memory Impairment in Children
Ketamine, an FDA approved anesthetic agent, is becoming the sedative/analgesic of choice for emergency sedation in children because it causes deep sedation with minimal respiratory depression in comparison to other available agents. However, emergence reactions are an important adverse effect of ketamine, characterized by transient changes in cognitive function, dissociation and mild schizophrenia-like symptoms. These cognitive and behavioral effects are dose-dependently induced by ketamine and other antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor. NMDA receptor hypofunction can disinhibit excitatory (cholinergic/glutamatergic) projections in key areas of the brain, and this has been proposed to explain key features of schizophrenia. Several treatments that block excessive excitatory transmitter release have also been shown to prevent cognitive and behavioral effects of ketamine-induced NMDA receptor hypofunction in humans. Alpha-2 adrenergic agonists, which can presynaptically inhibit acetylcholine release, can prevent mild ketamine-induced behavioral and cognitive symptoms in healthy human adults. However, this prevention strategy has not been evaluated in children. Children currently receive clinically-indicated treatment with the NMDA antagonist, ketamine, and this age group is an important target for pharmacological strategies aimed at the prevention of schizophrenia. This application proposes a double-blind, placebo-controlled, randomized trial to test the safety and effectiveness of dexmedetomidine, an FDA approved alpha-2 adrenergic agonist, in preventing ketamine-induced mental symptoms in children. Planned primary analyses will evaluate effects of the hypothesized prevention treatment on clinical and cognitive variables using analysis of variance (ANOVA). The proposed experiments are relevant to future prevention trials for individuals at risk for schizophrenia, and to preventing adverse effects of NMDA antagonist anesthetic agents (ketamine, nitrous oxide).
Read the detailed description
The proposed study will be conducted using existing dedicated clinical and research space in St. Louis Children's Hospital's Emergency Department, Pediatric Clinical Research Center (PCRC), and Orthopedic Clinic. This project has 3 major aims and 1 exploratory aim addressed by a prospective randomized blinded placebo controlled drug trial to test whether a pharmacological strategy can prevent NMDA receptor hypofunction-induced behavioral and cognitive dysfunction in pre- and post-pubertal children. Based on previous preclinical and clinical research on the effects and blockade of the effects of ketamine and similar compounds, the study investigators have carefully selected a dose of the alpha-2 adrenergic agonist dexmedetomidine that will permit this study to be conducted with low risk to enrolled subjects who are undergoing clinically-indicated ketamine sedation for forearm fracture reduction.
General Experimental Design: This project will test the safety and effectiveness of dexmedetomidine for preventing ketamine-induced behavioral and cognitive symptoms in healthy human children undergoing clinically indicated ketamine sedation for forearm fracture reduction.
Aims 1 and 2 will be addressed by randomized, blinded administration of dexmedetomidine or saline placebo to ketamine-sedated subjects to test the efficacy of dexmedetomidine in preventing ketamine-induced behavioral and cognitive changes during recovery from sedation.
Aim 3 will be addressed by comparing between the subjects randomized to receive dexmedetomidine or saline placebo measurements of distress and frequency of adverse cardiopulmonary effects during sedation, fracture-reduction, and recovery.
- Conditions
- Psychoses, Substance-Induced
- Being tested
- Ketamine, Dexmedetomidine
- Keywords
- NMDA antagonist-induced psychosis, Children, Memory Impairment, Decreased cognitive function, Increased memory impairment
- Medical subject headings
- Psychoses, Substance-Induced, Memory Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketanest, Ketaset, Ketalar
Ketamine without dexmedetomidine
DexmedetomidineDrug
Also called Precedex
Ketamine plus dexmedetomidine
| Study group | Role | What they receive |
|---|---|---|
| Ketamine plue saline | Placebo comparator | Ketamine without dexmedetomidine Receives: Drug: Ketamine |
| Ketamine plus dexmedetomidine | Experimental | Ketamine infusion plus dexmedetomidine Receives: Drug: Dexmedetomidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brief Psychiatric Ratings Scale (BPRS) Positive Symptom Subscale Score
Participant received behavioral ratings before medication and during medication for the primary analysis comparison. This is an observer-scale with a value range from 0-6 (0=no symptoms 6=worst symptoms)
Measured: Before Ketamine, During Ketamine
Secondary outcomes (2)
Visual Analog Scale (VAS) Pain Intensity
Pain intensity was measured on a scale of 1-10 (1=lowest pain intensity, 10=highest pain intensity) in participants before medication, during medication, post medication and 1 week follow up.
Measured: Before Ketamine, During Ketamine, Post Ketamine and 1 Week Follow up
Visual Analog Scale (VAS) Anxiety Rating
Anxiety was measured on a scale of 1-10 (1=lowest pain intensity, 10=highest pain intensity) in participants before medication, during medication, post medication and 1 week follow up.
Measured: Before Ketamine, During Ketamine, Post Ketamine, 1 week follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startFeb 2003
- Primary completionOct 2007
- Study completionOct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Psychoses, Substance-InducedStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression
- Responsible party
- Sponsor
- Investigators
- John W. Newcomer, M.D., Principal investigator, Washington University School of Medicine and Florida Atlantic University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00205712
- Sponsor's protocol ID
- NARSAD - Kids
- Other IDs
- 01-0886
- Status last verified
- Jan 2016
- First submitted
- 13 Sep 2005
- Last updated
- 14 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of NMDA Antagonist-induced Psychosis and Memory Impairment in Children
- ClinicalTrials.gov ID
- NCT00205712
- Acronym / sponsor ID
- NARSAD - Kids
- Conditions
- Psychoses, Substance-Induced
- Keywords
- NMDA antagonist-induced psychosis, Children, Memory Impairment, Decreased cognitive function, Increased memory impairment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression
- Study start
- Feb 2003
- Primary completion
- Oct 2007 (actual)
- Study completion
- Oct 2007 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Posted 7 Apr 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ketamine, an FDA approved anesthetic agent, is becoming the sedative/analgesic of choice for emergency sedation in children because it causes deep sedation with minimal respiratory depression in comparison to other available agents. However, emergence reactions are an important adverse effect of ketamine, characterized by transient changes in cognitive function, dissociation and mild schizophrenia-like symptoms. These cognitive and behavioral effects are dose-dependently induced by ketamine and other antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor. NMDA receptor hypofunction can disinhibit excitatory (cholinergic/glutamatergic) projections in key areas of the brain, and this has been proposed to explain key features of schizophrenia. Several treatments that block excessive excitatory transmitter release have also been shown to prevent cognitive and behavioral effects of ketamine-induced NMDA receptor hypofunction in humans. Alpha-2 adrenergic agonists, which can presynaptically inhibit acetylcholine release, can prevent mild ketamine-induced behavioral and cognitive symptoms in healthy human adults. However, this prevention strategy has not been evaluated in children. Children currently receive clinically-indicated treatment with the NMDA antagonist, ketamine, and this age group is an important target for pharmacological strategies aimed at the prevention of schizophrenia. This application proposes a double-blind, placebo-controlled, randomized trial to test the safety and effectiveness of dexmedetomidine, an FDA approved alpha-2 adrenergic agonist, in preventing ketamine-induced mental symptoms in children. Planned primary analyses will evaluate effects of the hypothesized prevention treatment on clinical and cognitive variables using analysis of variance (ANOVA). The proposed experiments are relevant to future prevention trials for individuals at risk for schizophrenia, and to preventing adverse effects of NMDA antagonist anesthetic agents (ketamine, nitrous oxide).
Detailed description
The proposed study will be conducted using existing dedicated clinical and research space in St. Louis Children's Hospital's Emergency Department, Pediatric Clinical Research Center (PCRC), and Orthopedic Clinic. This project has 3 major aims and 1 exploratory aim addressed by a prospective randomized blinded placebo controlled drug trial to test whether a pharmacological strategy can prevent NMDA receptor hypofunction-induced behavioral and cognitive dysfunction in pre- and post-pubertal children. Based on previous preclinical and clinical research on the effects and blockade of the effects of ketamine and similar compounds, the study investigators have carefully selected a dose of the alpha-2 adrenergic agonist dexmedetomidine that will permit this study to be conducted with low risk to enrolled subjects who are undergoing clinically-indicated ketamine sedation for forearm fracture reduction.
General Experimental Design: This project will test the safety and effectiveness of dexmedetomidine for preventing ketamine-induced behavioral and cognitive symptoms in healthy human children undergoing clinically indicated ketamine sedation for forearm fracture reduction.
Aims 1 and 2 will be addressed by randomized, blinded administration of dexmedetomidine or saline placebo to ketamine-sedated subjects to test the efficacy of dexmedetomidine in preventing ketamine-induced behavioral and cognitive changes during recovery from sedation.
Aim 3 will be addressed by comparing between the subjects randomized to receive dexmedetomidine or saline placebo measurements of distress and frequency of adverse cardiopulmonary effects during sedation, fracture-reduction, and recovery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine plue saline | Placebo comparator | Drug: KetamineKetamine without dexmedetomidine |
| Ketamine plus dexmedetomidine | Experimental | Drug: DexmedetomidineKetamine infusion plus dexmedetomidine |
Who may qualify
- Ages
- 7 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Patients presenting to St. Louis Children's Hospital's Emergency Department who require reduction of an acute forearm fracture will be recruited for enrollment if they satisfy the following:
- Age 7-17 years, inclusive;
- Are psychiatrically healthy (i.e. have never been under the care of a psychiatrist or taken psychiatrically active medications);
- Meet American Society of Anesthesiologist (ASA) Class I and II criteria (I=healthy, II=chronic disease under good control);
- Have had no prior fracture reduction or ketamine administration;
Key exclusion criteria (6 listed)
- Solid food intake 2 hours or less before procedure;
- Compromised cardiorespiratory function; central nervous system, hepatic, or renal abnormality;
- History of psychosis in patient or first degree relative;
- Currently taking medications that stimulate or depress mental function, e.g. methylphenidate for attention deficit hyperactivity disorder or drugs of abuse;
- History of allergy or adverse reaction to alpha-2 adrenoreceptor agonist drugs, e.g. clonidine.
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 |
|---|---|---|
| KetamineAlso: Ketanest, Ketaset, KetalarKetamine without dexmedetomidine | Drug | Ketamine plue saline |
| DexmedetomidineAlso: PrecedexKetamine plus dexmedetomidine | Drug | Ketamine plus dexmedetomidine |
Primary outcome
Brief Psychiatric Ratings Scale (BPRS) Positive Symptom Subscale Score
Time frame: Before Ketamine, During Ketamine
Participant received behavioral ratings before medication and during medication for the primary analysis comparison. This is an observer-scale with a value range from 0-6 (0=no symptoms 6=worst symptoms)
2 secondary outcomes
Visual Analog Scale (VAS) Pain Intensity
Time frame: Before Ketamine, During Ketamine, Post Ketamine and 1 Week Follow up
Visual Analog Scale (VAS) Anxiety Rating
Time frame: Before Ketamine, During Ketamine, Post Ketamine, 1 week follow up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Psychoses, Substance-Induced
Enrolling by invitation
Incentives and Long-Acting Injectable Adherence After Involuntary Hospitalization
Schizophrenia Disorder, Schizoaffective Disorder
Not yet recruitingPhase 2
An Investigation of Mechanisms That Underly Paranoia in Behaviour and Brain That Can Inform Clinical Diagnoses That Include Paranoid Symptoms.
None Volunteer
Recruiting
Circuitry-Guided Smoking Cessation in Schizophrenia (UH3)
Smoking Cessation, Nicotine Addiction
Recruiting
Investigating the Neural Correlates of Cognitive Function in Psychosis Patients and Non-Psychiatric Controls With Cannabis Use
Psychotic Disorders, Cannabis Use Disorder
Recruiting
Building Social and Structural Connections for the Prevention of Opioid Use Disorder Among Youth Experiencing Homelessness
Opioid Use Disorder, Dual Diagnosis
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.
John W. Newcomer, M.D. principal investigator
Washington University School of Medicine and Florida Atlantic University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketamine and Dexmedetomidine in people with Psychoses, Substance-Induced, run by Washington University School of Medicine at 1 site 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 8 inclusion and 6 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: finished, as of the sponsor's last update on 14 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Apr 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Brief Psychiatric Ratings Scale (BPRS) Positive Symptom Subscale Score (time frame: Before Ketamine, During Ketamine). 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 14 Jan 2016.