Will Decreased Noradrenergic Activity Normalize Information Processing in Patients With Schizophrenia?

Schizophrenia Clinical Trial

Official title:

Will Decreased Noradrenergic Activity Normalize Information Processing in Patients With Schizophrenia?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00206986
• Other study ID #: 363037-2
• Secondary ID: KF 11-261729
• Status: Completed
• Phase: N/A
• First received: September 12, 2005
• Last updated: December 19, 2013
• Start date: May 2005
• Est. completion date: December 2011

Study information

• Verified date: December 2013
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: National Board of Health
• Study type: Interventional

Clinical Trial Summary

The investigators want to try to improve information processing in schizophrenic patients via pharmacological intervention. The hypothesis is that decreased noradrenergic activity will normalize information processing (PPI, P50 gating, P300, and mismatch negativity) in patients with schizophrenia.

Description:

A number of reports in literature provide evidence for, among others, an increased central noradrenergic activity in schizophrenia. In addition to this increased noradrenergic activity, patients with schizophrenia often show reduced filtering of sensory information, which is reflected in reduced P50 suppression and reduced prepulse inhibition of the startle reflex (PPI). In two separate initial studies in our laboratory, we found reduced sensory gating following administration of imipramine (a combined noradrenergic and serotonergic agonist) and desipramine (a highly specific noradrenergic agonist) to healthy volunteers. This provides evidence for a direct causal relation between the increased noradrenergic activity and the disturbed gating of sensory information, as both commonly found in patients with schizophrenia. Therefore, in a follow-up study, the effects of a noradrenergic antagonist will be investigated on the sensory gating of patients with schizophrenia. To further extend the data of our initial studies, the patients will additionally be tested for two psychophysiological parameters of attention that are usually found to be disturbed in patients with schizophrenia, i.e. mismatch negativity and selective attention. The design will conform to a double blind, placebo controlled experiment, in which either four doses (0.25 ug, 50 ug, 75 ug or 150 ug)of clonidine or placebo will be added to the current medical treatment of 20 male patients with schizophrenia on five occasions, separated by at least a week, after which they are tested in the Copenhagen Psychophysiological Test Battery (CPTB).In order to test the effects of clonidine in healthy volunteers, 20 healthy males will receive a fixed dose of 0.15 mg clonidine or placebo on two separate occasions separated by at least a week, after which they will be tested in the CPTB as well.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Patients:

• Male subjects

• Meeting the DSM-IV diagnosis of schizophrenia

• Controls:

• Male subjects

• Good Physical and Mental Health meeting criteria "never mentally ill", which will be evaluated with a medical history checklist

• Non smokers

Exclusion Criteria:

• Patients:

• A P50 suppression or PPI score falling within a range of 10 percent above or below the mean score of the healthy control group

• Controls:

• Current use of any medication

• Any subject who has received any investigational medication within 30 days prior to the start of this study

• History of neurologic illness

• History of psychiatric illness in first-degree relatives, evaluated with DSM-IV criteria

• History of alcohol and drug abuse.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• clonidine
Either placebo or 25 ug, 50 uG 75 ug or 150 ug of clonidine will be added to the current medication of patients with schizophrenia, who are stable on their current medication
• clonidine
0.15 mg of clonidine will be administered to 20 healthy male volunteers

Locations

Country	Name	City	State
Denmark	Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup	Copenhagen NV

Sponsors (4)

Lead Sponsor	Collaborator
Birte Glenthoj	Glostrup University Hospital, Copenhagen, Lundbeck Foundation, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The following psychophysiological measures:		prospective	No
Primary	Prepulse Inhibition og the Startle Response (PPI)		Once, 3.5 hrs after intake of capsule	No
Primary	P50 suppression		Once, 3.5 hrs after intake of capsule	No
Primary	P300 Event Related Potential		Once, 3.5 hrs after intake of capsule	No
Primary	Mismatch negativity		Once, 3.5 hrs after intake of capsule	No
Primary	PANSS		5 times hourly after intake of capsule	No

External Links

•   Center for Neuropsychiatric Schizophrenia Research (CNSR)