The CAMPUS Project: Cholinergic Augmentation of Cognitive Deficits in Schizophrenia

This study has been terminated.
(No more funding)
Sponsor:
Collaborators:
Rigshospitalet, Denmark
Glostrup University Hospital, Copenhagen
Pfizer
Information provided by (Responsible Party):
Birte Glenthoj, University of Copenhagen
ClinicalTrials.gov Identifier:
NCT00206947
First received: September 11, 2005
Last updated: September 19, 2011
Last verified: July 2008
  Purpose

The present study will specify and delineate the separate components of cognitive deficits and examine the effects of adjunctive cholinergic augmentation on these cognitive deficits as well as psychopathology in schizophrenic patients treated with an antipsychotic compound with no aberrant binding affinity for the cholinergic receptor system. The hypothesis is that cholinergic augmentation using donepezil will improve cognitive deficits, sensory gating deficits, and psychopathology in schizophrenic patients treated with an atypical antipsychotic (ziprasidone).


Condition Intervention Phase
Schizophrenia
Drug: donepezil (5-10 mg/day)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: PHARMACOLOGICAL TREATMENT OF COGNITIVE DEFICITS IN SCHIZOPHRENIC PATIENTS: The Effects of Central Cholinergic Augmentation on Cognitive Deficits and Psychopathology

Resource links provided by NLM:


Further study details as provided by University of Copenhagen:

Primary Outcome Measures:
  • PANSS (Positive and Negative Symptom Scale) [ Time Frame: baseline and after treatment ] [ Designated as safety issue: No ]
  • the CGI (Clinical Global Impression scale) [ Time Frame: baseline and after treatment ] [ Designated as safety issue: No ]
  • the ESRS (Extrapyramidal Symptom Rating Scale) [ Time Frame: baseline and after treatment ] [ Designated as safety issue: No ]
  • Cognitive functions: A comprehensive test battery focuses on central cognitive deficits in schizophrenia: i.e. memory functions, attention, executive functions, reaction time, as well as pre-morbid and current intelligence. [ Time Frame: baseline and after treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • MRI [ Time Frame: baseline and after treatment ] [ Designated as safety issue: No ]
  • fMRI [ Time Frame: baseline and after treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: December 2002
Study Completion Date: January 2005
Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: donepezil (5-10 mg/day)
Donepezil will be administered in a dose optimized for treatment, to patients who are stabilized on a ziprasidone treatment
Other Name: Aricept, Zeldox
Placebo Comparator: 2 Drug: Placebo
Placebo will be added to the medication of schizophrenia patients who are first stabilized on a ziprasidone treatment
Other Name: Zeldox

Detailed Description:

The purpose of the study was to examine the effects of cholinergic augmentation of atypical antipsychotic medication on:

  • Cognitive deficits
  • Sensorimotor gating
  • Psychopathology

The primary objective was to examine:

• The effects of donepezil, compared to the effects of placebo, on cognitive function, sensorimotor gating and psychopathology in patients treated with an atypical antipsychotic (ziprasidone).

Secondary objectives are to examine:

  • The effect of donepezil, compared to the effects of placebo, on cognitive function, sensorimotor gating and psychopathology in patients treated with ziprasidone.
  • Which specific areas of cognitive deficits benefit from cholinergic augmentation of atypical antipsychotic treatment.
  • The interactions between cognitive deficits and psychopathology: To what extent the effects of cholinergic augmentation on psychopathology, sensorimotor gating, and cognition are independent or correlated.
  • Which specific brain areas are activated during cholinergic augmentation of treatment with an atypical antipsychotic drug (ziprasidone).

Participants: Schizophrenic men and women between the ages 18 to 55 who meet the ICD-10 criteria for schizophrenia living in the catchment area of the psychiatric departments of Bispebjerg University Hospital,Rigshospitalet, or Psychiatric Center, Glostrup. Patients can be either unmedicated, or need to be switched from other antipsychotic medications due to side-effects, or lack of effect on negative symptoms, positive symptoms, or cognitive function. Patients can be enrolled in the study as inpatients or outpatients, and changes in hospitalization status during the trial are allowed. Patients were stabilized on antipsychotic medication (ziprasidone) before they were randomized to treatment with either donepezil or placebo.

  Eligibility

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

Inclusion Criteria:

  • Patients: Men and women between the ages 18 to 55 who meet the ICD-10 criteria for schizophrenia living in the catchment area of the psychiatric departments of Bispebjerg University Hospital, Psychiatric Center, Glostrup and Rigshospitalet. Patients can be either unmedicated, or need to be switched from other antipsychotic medications due to side-effects, or lack of effect on negative symptoms, positive symptoms, or cognitive function.
  • Controls: Healthy men and women matched according to gender, age, and socio-economic status (determined by the level of education and income of parents).

Exclusion Criteria:

  • Patients: Patients hospitalized against their will. Patients with a serious medical illness or with laboratory abnormalities, where pharmacotherapy poses a substantial clinical risk; pregnant or lactating patients; patients with organic psychosis, a history of severe head trauma or convulsive disorders, or patients with mental retardation. Patients with significant alcohol- or drug dependence are excluded.
  • Controls: Pregnant or lactating women; a history of severe head trauma; mental retardation; learning difficulties; a history of psychiatric illness or a familial predisposition to psychiatric illness (in first-degree relatives); significant alcohol- or drug dependence; episodic incidents of excessive alcohol consumption or drug abuse are not reasons for exclusion. Abuse is monitored by interviewing patients and by measuring the urine content for amphetamine, cannabinoles, opiates, and benzodiazepines. Concomitant use of benzodiazepines for agitation or insomnia (oxazepam up to 45 mg daily) is allowed when needed and when used conservatively during the trial. Use of anticholinergic compounds is not allowed.
  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: NCT00206947

Locations
Denmark
Dept. of Psychiatry O, Rigshospitalet, Blegdamsvej 9
Copenhagen, Denmark, DK-2100
Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Dept. F, Bispebjerg Hospital
Copenhagen NV, Denmark, DK-2400
Psychiatric Center, Glostrup
Glostrup, Denmark, DK-2600
Danish Research Center for Magnetic Resonance Imaging, Hvidovre Hospital
Hvidovre, Denmark, DK-2650
Sponsors and Collaborators
Birte Glenthoj
Rigshospitalet, Denmark
Glostrup University Hospital, Copenhagen
Pfizer
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: NCT00206947     History of Changes
Other Study ID Numbers: 363051, KF 02-033/02, DMA 2612-2013
Study First Received: September 11, 2005
Last Updated: September 19, 2011
Health Authority: Denmark: National Board of Health

Keywords provided by University of Copenhagen:
Cognitive deficits
Cholinergic Augmentation
Schizophrenia

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Cholinergic Agents
Donepezil
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Cholinesterase Inhibitors
Enzyme Inhibitors
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014