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

Brain Network Dysfunction as a Model for Schizophrenia: Connectivity Alterations Using Ketamine and Pharmacological Magnetic Resonance Imaging

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Esketamine hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Department of Psychiatry and Psychotherapy, Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ketamine-induced changes in BOLD-activity over time	participants will be measured twice and all participants are expected to be recruited and measured within 1 year	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Change of task-induced BOLD-activity by ketamine application	60 minutes (before and after ketamine infusion) at each MRI session (interval between MRI scans: 1 week)

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Rupert Lanzenberger, A/Prof., MD, Department of Psychiatry and Psychotherapy, Medical University of Vienna

Publications and helpful links

Helpful Links

• Homepage of the Functional Neuroimaging Group, Department of Psychiatry and Psychotherapy, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: July 13, 2011
• First Submitted That Met QC Criteria: July 13, 2011
• First Posted (Estimate): July 14, 2011

Study Record Updates

• Last Update Posted (Estimate): December 31, 2013
• Last Update Submitted That Met QC Criteria: December 29, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Psychotropic Drugs; Antidepressive Agents; Ketamine; Esketamine
• Other Study ID Numbers: P14193ONB; 2010-022772-31 (EudraCT Number)