A Study of the Effectiveness and Safety of Galantamine Hydrobromide on Cognitive Impairment in Patients With Schizophrenia.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00077727
Recruitment Status : Completed
First Posted : February 16, 2004
Last Update Posted : May 24, 2011
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Brief Summary:
The purpose of this study is to determine if adding extended-release galantamine hydrobromide, compared with adding placebo, to current atypical antipsychotic therapy is well tolerated and effective in improving cognitive impairment in patients with schizophrenia.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Extended-release galantamine hydrobromide Phase 3

Detailed Description:
Galantamine acts on acetylcholinesterase, and has been shown to effectively treat cognitive symptoms in patients with Alzheimer's disease. Previous cellular research of nicotinic receptors has shown promising results, and it is theorized that the nicotinic system of patients with schizophrenia may be abnormal and may play an important role in the cognitive symptoms associated with schizophrenia. It is also postulated that galantamine may improve neuropsychiatric symptoms such as hallucinations, delusions, and apathy in patients with Alzheimer's disease. Atypical antipsychotic medications are effective treatment for schizophrenia patients but some symptoms remain. Therefore, galantamine may be a useful cotreatment for schizophrenia patients on atypical antipsychotic treatment. This is a pilot dose-ranging, randomized (patients are assigned different treatments based on chance), double-blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage), placebo-controlled multicenter study that examines the effects of taking extended-release galantamine hydrobromide (16 or 24 mg once daily) or placebo on the effectiveness in reducing symptoms of schizophrenia patients who are already taking an atypical antipsychotic medication. The safety of combined treatment is also examined. Measures of effectiveness include the Positive and Negative Syndrome Scale (PANSS) to measure neuropsychiatric symptoms of schizophrenia; the Clinical Global Impression (CGI) scale to measure change over the course of the study; the Brief Assessment of Cognition in Schizophrenia (BACS) for verbal memory and learning, working memory, motor function, attention, verbal fluency, and executive functioning; the Continuous Performance Test (CPT) for sustained attention and distractability; reaction time test (RTT) and finger tapping test (FTT) for psychomotor speed; Lexical and Semantic Fluency Test (LSFT) for language skills. As schizophrenia patients are a population with high nicotine use, and galantamine may act on nicotine receptors, blood levels of nicotine are also measured as varying nicotine levels could alter the effects of galantamine. The null hypothesis that there is no difference between the 2 groups (galantamine cotreatment and placebo) will be tested for each of the efficacy measurements (total PANSS, BACS, and CGI scores) at Week 8. Measures of safety include physical examinations, electrocardiograms (ECGs), clinical laboratory tests, measurement of plasma prolactin concentrations, pregnancy test for women, and incidence of adverse events. Adverse events that might be related to the medications are also monitored using the Simpson-Angus Extrapyramidal Side Effects Scale (SAS), the Barnes Akathisia Rating Scale (BARS), and the Abnormal Involuntary Movement Scale (AIMS). Extended-release galantamine hydrobromide or matching placebo capsules for once-daily dosing. Patients take 8 milligrams (mg) per day during Week 1, 16 mg per day during Week 2, and 16 mg or 24 mg per day (depending on randomization) during Weeks 3 to 8. Treatment groups are placebo capsule, 16 mg capsule, 24 mg capsule.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 107 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: A Study of Galantamine HBr as an Adjunctive Treatment to Atypical Antipsychotic Medications in Outpatients With Schizophrenia and Associated Cognitive Deficits.
Study Start Date : March 2003
Actual Study Completion Date : February 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Primary Outcome Measures :
  1. The key exploratory efficacy end points are the change from baseline to Week 8 in total PANSS score, total BACS score, and CGI global improvement and severity of illness scores.

Secondary Outcome Measures :
  1. Additional efficacy assessments included subscore analyses for LSFT, CPT, RTT and FTT.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of schizophrenia present for at least 1 year, and has not returned to his/her level of functioning before the disease, with a Brief Psychiatric Rating Scale score of 30 to 60 (inclusive), and cognitive impairment as determined by scores from neuropsychological tests and subtests
  • Nicotine user with a minimum intake equivalent to 5 cigarettes per day
  • On a stable dose of allowed atypical antipsychotic medication (risperidone [either oral or CONSTA], olanzapine, quetiapine, ziprasidone, or aripiprazole) alone or in combination, for at least 30 days before screening, and deemed able to continue on the same dose
  • Women patients must be postmenopausal, surgically sterile, or using appropriate contraception before entry and throughout the study, and have a negative pregnancy test at screening
  • Able to read, write, and understand English, and has no limitations in communication skills that would prevent him/her from completing the cognitive tests used in this study.

Exclusion Criteria:

  • Previously enrolled in a galantamine hydrobromide study
  • Any clinically significant uncontrolled medical illness (such as peptic ulcer disease
  • urinary tract obstruction
  • or neurologic, cardiac, hepatic, renal, metabolic, or endocrine disturbances)
  • History of severe asthma
  • Any history of epilepsy or convulsions, except for febrile convulsions during childhood
  • History of cancer within the past year, except for treated basal cell carcinoma, or any history of prolactin-dependent breast cancer

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00077727

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Additional Information: Identifier: NCT00077727     History of Changes
Other Study ID Numbers: CR004366
First Posted: February 16, 2004    Key Record Dates
Last Update Posted: May 24, 2011
Last Verified: April 2010

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
cognitive impairment
acetylcholinesterase inhibitors
antipsychotic drugs

Additional relevant MeSH terms:
Cognitive Dysfunction
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Cognition Disorders
Neurocognitive Disorders
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Autonomic Agents
Peripheral Nervous System Agents
Nootropic Agents