Network Dysfunction, Schizophrenia and Pharmacological Magnetic Resonance Imaging (phMRI)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rupert Lanzenberger, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01394757
First received: July 13, 2011
Last updated: December 29, 2013
Last verified: December 2013
  Purpose

Alterations of functional brain networks have been frequently demonstrated in schizophrenia, although the exact underlying molecular mechanisms remain unrevealed. Ketamine is known to exert its schizophrenia-like effects through modulation of the glutamatergic system, thus facilitating the investigation of the impact of this specific transmitter system on resting state functional brain networks. The aim of the study is therefore to use pharmacological functional Magnetic Resonance Imaging (phMRI) to examine changes in brain networks involved in schizophrenia in response to ketamine application compared to placebo. 30 healthy subjects (15 females) will be examined twice using a double-blind, placebo-controlled, randomized, crossover, counterbalanced-order design. Resting state fMRI will be investigated before, during and after either placebo or ketamine intravenous infusion for 20 minutes. Prior to the main trial 10 additional participants will be included in an open pilot trial.

Hypothesis: Ketamine application will induce changes in resting state networks previously associated with schizophrenia and in the connectivity of relevant brain regions such as the striatum, thalamus, caudate, hippocampus and amygdala. Furthermore, the application of ketamine will provoke changes in the BOLD-activation in three fMRI paradigms each performed before and after ketamine infusion.


Condition Intervention
Healthy Volunteers
Drug: Esketamine hydrochloride

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Brain Network Dysfunction as a Model for Schizophrenia: Connectivity Alterations Using Ketamine and Pharmacological Magnetic Resonance Imaging

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Ketamine-induced changes in BOLD-activity over time [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    participants will be measured twice and all participants are expected to be recruited and measured within 1 year


Secondary Outcome Measures:
  • Change of task-induced BOLD-activity by ketamine application [ Time Frame: 60 minutes (before and after ketamine infusion) at each MRI session (interval between MRI scans: 1 week) ] [ Designated as safety issue: No ]

Enrollment: 52
Study Start Date: August 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Esketamine hydrochloride
    Bolus: 15 mg/kg over 1 minute, followed by a maintenance infusion of 0.25 mg/kg/h for 19 minutes.
    Other Names:
    • Ketanest S
    • Ketamine
  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • general health based on history, physical examination, ECG, laboratory screening and structured clinical interview for DSM-IV(SCID)
  • willingness and competence to sign the informed consent form
  • aged 18 to 55 years

Exclusion Criteria:

  • any medical, psychiatric or neurological illness
  • current or former substance abuse
  • any implant or stainless steel graft and any other contraindications for MRI
  • pregnancy
  • first degree relatives with a history of psychiatric illness or substance abuse
  • failures to comply with the study protocol or to follow the instructions of the investigating team
  • lifetime use of antipsychotic drugs
  • treatment with psychotropic agents such as SSRIs within the last 6 months
  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: NCT01394757

Locations
Austria
Department of Psychiatry and Psychotherapy, Medical University of Vienna
Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Rupert Lanzenberger, A/Prof., MD Department of Psychiatry and Psychotherapy, Medical University of Vienna
  More Information

Additional Information:
No publications provided

Responsible Party: Rupert Lanzenberger, A/Prof. PD Dr., Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01394757     History of Changes
Other Study ID Numbers: P14193ONB, 2010-022772-31
Study First Received: July 13, 2011
Last Updated: December 29, 2013
Health Authority: Austria: Human Research Ethics Committee, Medical University of Vienna
Austria: Austrian Agency for Health and Food Safety

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

ClinicalTrials.gov processed this record on July 23, 2014