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

This study has been completed.
Sponsor:
Collaborators:
University of Copenhagen
Lundbeck Foundation
Glostrup University Hospital, Copenhagen
Information provided by (Responsible Party):
Birte Glenthoj, University of Copenhagen
ClinicalTrials.gov Identifier:
NCT00206986
First received: September 12, 2005
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention
Schizophrenia
Drug: clonidine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Will Decreased Noradrenergic Activity Normalize Information Processing in Patients With Schizophrenia?

Resource links provided by NLM:


Further study details as provided by University of Copenhagen:

Primary Outcome Measures:
  • The following psychophysiological measures: [ Time Frame: prospective ] [ Designated as safety issue: No ]
  • Prepulse Inhibition og the Startle Response (PPI) [ Time Frame: Once, 3.5 hrs after intake of capsule ] [ Designated as safety issue: No ]
  • P50 suppression [ Time Frame: Once, 3.5 hrs after intake of capsule ] [ Designated as safety issue: No ]
  • P300 Event Related Potential [ Time Frame: Once, 3.5 hrs after intake of capsule ] [ Designated as safety issue: No ]
  • Mismatch negativity [ Time Frame: Once, 3.5 hrs after intake of capsule ] [ Designated as safety issue: No ]
  • PANSS [ Time Frame: 5 times hourly after intake of capsule ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: May 2005
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 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
Other Name: Catapressan
Experimental: 2 Drug: clonidine
0.15 mg of clonidine will be administered to 20 healthy male volunteers
Other Name: Catapressan

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00206986

Locations
Denmark
Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup
Copenhagen NV, Denmark, DK-2400
Sponsors and Collaborators
Birte Glenthoj
University of Copenhagen
Lundbeck Foundation
Glostrup University Hospital, Copenhagen
Investigators
Study Director: Birte Glenthoj, MD, DMSc. Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychaitric Center Glostrup, Ndr. Ringvej, DK-2600 Glostrup, Denmark
  More Information

Additional Information:
No publications provided

Responsible Party: Birte Glenthoj, Professor, University of Copenhagen
ClinicalTrials.gov Identifier: NCT00206986     History of Changes
Other Study ID Numbers: 363037-2, KF 11-261729
Study First Received: September 12, 2005
Last Updated: December 19, 2013
Health Authority: Denmark: National Board of Health

Keywords provided by University of Copenhagen:
Schizophrenia
Information processing
PPI
P50 gating
P300
mismatch negativity
clonidine

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Clonidine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 10, 2014