The Effect of Ketamine on Attentiveness

This study has been completed.
Sponsor:
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT01165294
First received: July 15, 2010
Last updated: August 5, 2010
Last verified: August 2010
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Placebo
Drug: ketamine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
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)

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Cerebral activation of ketamine as determined by functional MRI [ Time Frame: 25 and 40 minutes after end of bolus injection of ketamine/placebo ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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). ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: October 2009
Study Completion Date: May 2010
Arms Assigned Interventions
Experimental: 001
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.
Drug: 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.
Experimental: 002
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
Drug: 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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01165294

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

No publications provided

Responsible Party: Director, Janssen Pharmaceutica N.V., Belgium
ClinicalTrials.gov Identifier: NCT01165294     History of Changes
Other Study ID Numbers: CR017368
Study First Received: July 15, 2010
Last Updated: August 5, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Ketamine

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014