The Effect of Ketamine on Attentiveness
Primary Purpose
Schizophrenia
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Placebo
ketamine
Sponsored by
About this trial
This is an interventional basic science trial for Schizophrenia focused on measuring Ketamine
Eligibility Criteria
Inclusion Criteria:
- Normal ECG and safety assessments, or minor no-relevant deviations, at screening
- Vital signs: systolic between 100 and 140 mmHg and diastolic between 50 and 90 mmHg and heart rate between 45 and 90 beats/min
- No medication intake in the last four weeks
- Volunteers must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study and to adhere to the prohibitions and restrictions specified in the protocol
- Negative drug screen
Exclusion Criteria:
- Participation in another clinical trial in the last 3 months
- Significant allergies, allergic diathesis or known hypersensitivity for ketamine or its ingredients (ie, Benzethonium chloride)
- History of or current significant respiratory disease, cardiovascular disease, endocrinological, gastrointestinal, neurological, glaucoma and known liver and kidney failure
- Contraindications for an MRI being performed (claustrophobia, metal parts, pacemaker)
- oxygen saturation pO2 < 90 mmHg
- Clinically significant abnormalities in ECG or laboratory values
- Recent history (within previous 6 months) of alcohol or drug abuse
- History of or current psychiatric diagnoses (DSM-IV, II) or neurological disorders
- Relatives in first or second degree with a schizophrenic disorder
- Serology positive for hepatitis B surface antigen, hepatitis C antibodies or HIV antibodies
- Signs of hyperthyroidism based on the determination of T3, T4 and TSH
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
001
002
Arm Description
ketamine An intravenous bolus of 0.1 mg/kg will be given in 5 minutes followed by a 1 minute break after which a continuous infusion will start at 0.015625 mg/kg/min.
Placebo An intravenous bolus will be given in 5 minutes time followed by a 1 minute break after which a continuous infusion will start. Dosage lowered every 10 minutes
Outcomes
Primary Outcome Measures
Cerebral activation of ketamine as determined by functional MRI
Cerebral activation of ketamine as determined by electroencephalogram (EEG) during an oddball-task
Secondary Outcome Measures
Effect of Ketamine on consciousness as measured by the "Altered States of Consciousness Rating Scale"
Cerebral activation induced by ketamine as measured by simultaneous fMRI / EEG under resting conditions
Symptom score of ketamine as measured with the Positive And Negative Symptom Scale
Full Information
NCT ID
NCT01165294
First Posted
July 15, 2010
Last Updated
August 5, 2010
Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
1. Study Identification
Unique Protocol Identification Number
NCT01165294
Brief Title
The Effect of Ketamine on Attentiveness
Official Title
Investigate the Effect of S-Ketamine, as Pharmacological Model of Schizophrenia, on the Attentiveness and Working Memory Simultaneously Measured With Functional Magnetic Resonance Imaging(fMRI)/Electroencephalogram(EEG)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2010
Overall Recruitment Status
Completed
Study Start Date
October 2009 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
May 2010 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
4. Oversight
5. Study Description
Brief Summary
The objective of this study is to develop an exploratory design for future Proof-of-Concept trials which reliably and accurately measure the central nervous system (CNS) effects of potentially new drugs that oppose the effects of ketamine at a subanesthetic dose level given to healthy volunteers. A functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) performed simultaneously during a ketamine challenge will register the effects triggered by Ketamine.
Detailed Description
This will be a double-blind (neither physician nor patient knows the name of the assigned drug), placebo-controlled, randomized (study drug assigned by chance), 2 way crossover ketamine challenge study (participants may receive different interventions sequentially during the trial) in 24 healthy male volunteers. For all participants, this study will consist of an eligibility screening examination, two 2-day treatment periods, separated by at least 1 week, and a follow-up examination about 7 days after last dose administration. The maximal study participation for each volunteer will be around 6 weeks. Apart from observing possible neural and vascular ketamine effects, the cerebral ketamine effects will be investigated by simultaneously performing fMRI/EEG during ketamine administration. These investigations will be done while volunteers rest as well as during cognitive testing (visual oddball task). Safety evaluations include continuous monitoring of vital signs and oxygen saturation. Due to the pharmacokinetic properties of ketamine the assessments will start after an intravenous ketamine bolus (drug given directly into the vein over a short period of time) followed by a 1 minute break. During the assessments there is a continuous intravenous (minimal) drug administration. Before the assessments start there will be an intravenous bolus of 0.1 mg/kg ketamine in 5 minutes time followed by a 1 minute break after which a continuous infusion will start of 0.015625 mg/kg/min ketamine. Since the plasma level elevates during the infusion the administered dose will be lowered by 10% every 10 minutes.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Ketamine
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
001
Arm Type
Experimental
Arm Description
ketamine An intravenous bolus of 0.1 mg/kg will be given in 5 minutes followed by a 1 minute break after which a continuous infusion will start at 0.015625 mg/kg/min.
Arm Title
002
Arm Type
Experimental
Arm Description
Placebo An intravenous bolus will be given in 5 minutes time followed by a 1 minute break after which a continuous infusion will start. Dosage lowered every 10 minutes
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
An intravenous bolus will be given in 5 minutes time followed by a 1 minute break after which a continuous infusion will start. Dosage lowered every 10 minutes
Intervention Type
Drug
Intervention Name(s)
ketamine
Intervention Description
An intravenous bolus of 0.1 mg/kg will be given in 5 minutes followed by a 1 minute break after which a continuous infusion will start at 0.015625 mg/kg/min.
Primary Outcome Measure Information:
Title
Cerebral activation of ketamine as determined by functional MRI
Time Frame
25 and 40 minutes after end of bolus injection of ketamine/placebo
Title
Cerebral activation of ketamine as determined by electroencephalogram (EEG) during an oddball-task
Time Frame
25 and 40 minutes after end of bolus injection of ketamine/placebo
Secondary Outcome Measure Information:
Title
Effect of Ketamine on consciousness as measured by the "Altered States of Consciousness Rating Scale"
Time Frame
60 min after end of bolus injection of ketamine.
Title
Cerebral activation induced by ketamine as measured by simultaneous fMRI / EEG under resting conditions
Time Frame
0 and 25 min after end of bolus injection of ketamine.
Title
Symptom score of ketamine as measured with the Positive And Negative Symptom Scale
Time Frame
60 min after end of bolus injection of ketamine (= at the end of ketamine infusion).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Normal ECG and safety assessments, or minor no-relevant deviations, at screening
Vital signs: systolic between 100 and 140 mmHg and diastolic between 50 and 90 mmHg and heart rate between 45 and 90 beats/min
No medication intake in the last four weeks
Volunteers must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study and to adhere to the prohibitions and restrictions specified in the protocol
Negative drug screen
Exclusion Criteria:
Participation in another clinical trial in the last 3 months
Significant allergies, allergic diathesis or known hypersensitivity for ketamine or its ingredients (ie, Benzethonium chloride)
History of or current significant respiratory disease, cardiovascular disease, endocrinological, gastrointestinal, neurological, glaucoma and known liver and kidney failure
Contraindications for an MRI being performed (claustrophobia, metal parts, pacemaker)
oxygen saturation pO2 < 90 mmHg
Clinically significant abnormalities in ECG or laboratory values
Recent history (within previous 6 months) of alcohol or drug abuse
History of or current psychiatric diagnoses (DSM-IV, II) or neurological disorders
Relatives in first or second degree with a schizophrenic disorder
Serology positive for hepatitis B surface antigen, hepatitis C antibodies or HIV antibodies
Signs of hyperthyroidism based on the determination of T3, T4 and TSH
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
Organizational Affiliation
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Official's Role
Study Director
12. IPD Sharing Statement
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The Effect of Ketamine on Attentiveness
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