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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01394757
• Other study ID #: P14193ONB
• Secondary ID: 2010-022772-31
• Status: Completed
• Phase: N/A
• First received: July 13, 2011
• Last updated: December 29, 2013
• Start date: August 2011
• Est. completion date: August 2012

Study information

• Verified date: December 2013
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Human Research Ethics Committee, Medical University of ViennaAustria: Austrian Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Esketamine hydrochloride
Bolus: 15 mg/kg over 1 minute, followed by a maintenance infusion of 0.25 mg/kg/h for 19 minutes.

Locations

Country	Name	City	State
Austria	Department of Psychiatry and Psychotherapy, Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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)	No

External Links

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