NCT00205712

Brief 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. 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).

Trial Health

87
On Track

Trial Health Score

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

Enrollment
40

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Feb 2003

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

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

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2003

Completed
2.6 years until next milestone

First Submitted

Initial submission to the registry

September 13, 2005

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 20, 2005

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2007

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2007

Completed
2.5 years until next milestone

Results Posted

Study results publicly available

April 7, 2010

Completed
Last Updated

January 14, 2016

Status Verified

January 1, 2016

Enrollment Period

4.7 years

First QC Date

September 13, 2005

Results QC Date

October 27, 2009

Last Update Submit

January 12, 2016

Conditions

Psychoses, Substance-Induced

Keywords

NMDA antagonist-induced psychosisChildrenMemory ImpairmentDecreased cognitive functionIncreased memory impairment

Outcome Measures

Primary Outcomes (1)

  • 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)

    Before Ketamine, During Ketamine

Secondary Outcomes (2)

  • Visual Analog Scale (VAS) Pain Intensity

    Before Ketamine, During Ketamine, Post Ketamine and 1 Week Follow up

  • Visual Analog Scale (VAS) Anxiety Rating

    Before Ketamine, During Ketamine, Post Ketamine, 1 week follow up

Study Arms (2)

Ketamine plue saline

PLACEBO COMPARATOR

Ketamine without dexmedetomidine

Drug: Ketamine

Ketamine plus dexmedetomidine

EXPERIMENTAL

Ketamine infusion plus dexmedetomidine

Drug: Dexmedetomidine

Interventions

KetamineDRUG

Ketamine without dexmedetomidine

Also known as: Ketanest, Ketaset, Ketalar
Ketamine plue saline
DexmedetomidineDRUG

Ketamine plus dexmedetomidine

Also known as: Precedex
Ketamine plus dexmedetomidine

Eligibility Criteria

Age7 Years - 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Washington University School of Medicine, Psychiatry Dept.

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Psychoses, Substance-InducedMemory Disorders

Interventions

KetamineDexmedetomidine

Condition Hierarchy (Ancestors)

PoisoningChemically-Induced DisordersSubstance-Related DisordersPsychotic DisordersSchizophrenia Spectrum and Other Psychotic DisordersMental DisordersNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
John Newcomer, MD
Organization
Washington University School of Medicine
newcomerj@wustl.edu
314-362-3153

Study Officials

  • John W. Newcomer, M.D.

    Washington University School of Medicine and Florida Atlantic University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 13, 2005

First Posted

September 20, 2005

Study Start

February 1, 2003

Primary Completion

October 1, 2007

Study Completion

October 1, 2007

Last Updated

January 14, 2016

Results First Posted

April 7, 2010

Record last verified: 2016-01

Locations

US(1)