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This is a 6-week, randomized, double blind, parallel groups designed, olanzapine-controlled trial of oral dipyridamole in symptomatic patients with a (DSM IV) diagnosis of schizophrenia, schizoaffective or schizophreniform disorder. This pilot study aims to provide preliminary estimates of whether the effect sizes of dipyridamole on positive symptoms, negative symptoms, and cognitive deficits differ between schizophrenia patients treated with dipyridamole, and schizophrenia patients treated with olanzapine. A total of 30 subjects will be recruited locally.
Since the demonstrated success of chlorpromazine in treating psychosis in the1950's, the pharmacotherapy of schizophrenia has focused mainly on drugs with antidopaminergic actions. These drugs have robust effects on reality distortion and disorganization symptom complexes, but minimal effect on cognitive impairment, negative symptoms, and functional outcome and quality of life measures. Newer generation antipsychotic drugs have a similar profile of effects, with some advantages on the course of depression, hostility, suicide, hospital readmission rates and motor side effect measures. Side effects such as weight gain, increase in cardiovascular stress and diabetes risk are associated with some new generation drugs. A new class of drugs is needed to address the inadequate effectiveness and the side-effect disadvantages of the currently available pharmacological agents for the treatment of schizophrenia. Recently, new treatment strategies using nicotinergic drugs or agonists at the glycine modulatory site of the glutamatergic N-methyl-D-aspartate (NMDA) receptor have been employed in clinical trials with mixed results. Our proposal focuses on a clinically available adenosine agonist, dipyridamole, in a 6-week clinical trial. Published data suggest effectiveness of dipyridamole in treating psychosis when added to haloperidol treatment. The effectiveness of dipyridamole alone in treating schizophrenia symptoms, although indirectly suggested by several lines of evidence, has not been tested.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Dipyridamole |
|
| 2 | Active Comparator | Olanzapine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dipyridamole | Drug | Week 1- 50 mg bid Week 2- 50 mg am and 100 mg pm Weeks 3-6 100 mg am and 100 mg pm |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Positive Symptoms by Treatment Assignment | The Brief Psychiatric Rating Scale (BPRS) consists of 20 items, with 6 of these items used to assess positive symptom change. The BPRS positive symptom items are: somatic concern, conceptual disorganization, hostility, suspiciousness, hallucinatory behavior, and unusual thought content. Each scale ranges from "1=Not Present" to "7=Very Severe". A higher score indicates a more severe positive symptom rating. | Baseline and follow-up |
| Change in Negative Symptoms by Treatment Assignment | The Scale for the Assessment of Negative Symptoms (SANS) total score, minus the global items, inappropriate affect, poverty of content of speech, and attention items, used to measure negative symptoms. Mean SANS total score by treatment and week. SANS total score range = 0-85. Higher scores indicate more severe negative symptoms. | Baseline and Follow-Up |
| The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) | The RBANS is a brief, individually administered test designed to evaluate neuropsychological status of adults, ages 20-89. The 12 subtests measure attention, language, visuospatial/constructional abilities, and immediate and delayed memory. The raw scores from the subtests are scaled together to create index scores, and these are summed for conversion to a total scale score. Higher score equals a better outcome. The total index score range for the RBANS is 40-160. | Baseline and Follow-Up |
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Inclusion Criteria:
Exclusion Criteria:
Patients with moderate to severe mental retardation.
Inability to sign informed consent.
Patients with a history of serious violence (e.g., suicide attempts, or assaultive behavior).
Patients on clozapine treatment within the 6 weeks leading to the double-blind phase.
Patients with a history of olanzapine non-response
Positive Urine Toxicology Screen
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| Name | Affiliation | Role |
|---|---|---|
| Ikwunga Wonodi, MD | Maryland Pschiatric Research Center, University of Maryland School of Medicine | Study Director |
| Gunvant K Thaker, MD | University of Maryland, College Park | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maryland Psychiatric Research Center | Baltimore | Maryland | 21228 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10849191 | Result | Akhondzadeh S, Shasavand E, Jamilian H, Shabestari O, Kamalipour A. Dipyridamole in the treatment of schizophrenia: adenosine-dopamine receptor interactions. J Clin Pharm Ther. 2000 Apr;25(2):131-7. doi: 10.1046/j.1365-2710.2000.00273.x. | |
| 10332540 | Result | Dixon DA, Fenix LA, Kim DM, Raffa RB. Indirect modulation of dopamine D2 receptors as potential pharmacotherapy for schizophrenia: I. Adenosine agonists. Ann Pharmacother. 1999 Apr;33(4):480-8. doi: 10.1345/aph.18215. |
| Label | URL |
|---|---|
| Maryland Psychiatric Research Center | View source |
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Four participants were excluded prior to randomization (1:positive urine tox screen; 1:participant uncooperative with clinical interview; 1:withdrew consent; 1:history of cardiovascular disease).
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| ID | Title | Description |
|---|---|---|
| FG000 | Dipyridamole | Dipyridamole Dipyridamole : Week 1- 50 mg bid Week 2- 50 mg am and 100 mg pm Weeks 3-6 100 mg am and 100 mg pm |
| FG001 | Olanzapine | Olanzapine Olanzapine : Week 1- 5 mg BID Week 2- 5 mg am and 10 mg pm Weeks 3-6 10 mg am and 10 mg pm |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dipyridamole | Dipyridamole Dipyridamole : Week 1- 50 mg bid Week 2- 50 mg am and 100 mg pm Weeks 3-6 100 mg am and 100 mg pm |
| BG001 | Olanzapine | Olanzapine Olanzapine : Week 1- 5 mg BID Week 2- 5 mg am and 10 mg pm Weeks 3-6 10 mg am and 10 mg pm |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Positive Symptoms by Treatment Assignment | The Brief Psychiatric Rating Scale (BPRS) consists of 20 items, with 6 of these items used to assess positive symptom change. The BPRS positive symptom items are: somatic concern, conceptual disorganization, hostility, suspiciousness, hallucinatory behavior, and unusual thought content. Each scale ranges from "1=Not Present" to "7=Very Severe". A higher score indicates a more severe positive symptom rating. | Participants completing the BPRS assessment. | Posted | Mean | Standard Deviation | units on a scale | Baseline and follow-up |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dipyridamole | Dipyridamole Dipyridamole : Week 1- 50 mg bid Week 2- 50 mg am and 100 mg pm Weeks 3-6 100 mg am and 100 mg pm |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Elliot Hong, Prinicipal Investigator | University of Maryland, Baltimore | 410-402-6828 | ehong@som.umaryland.edu |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D011618 | Psychotic Disorders |
| D003072 | Cognition Disorders |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D019965 | Neurocognitive Disorders |
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| ID | Term |
|---|---|
| D004176 | Dipyridamole |
| D000077152 | Olanzapine |
| ID | Term |
|---|---|
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001569 | Benzodiazepines |
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| Olanzapine |
| Other |
Week 1- 5 mg BID Week 2- 5 mg am and 10 mg pm Weeks 3-6 10 mg am and 10 mg pm |
|
| 9342776 | Result | Ferre S. Adenosine-dopamine interactions in the ventral striatum. Implications for the treatment of schizophrenia. Psychopharmacology (Berl). 1997 Sep;133(2):107-20. doi: 10.1007/s002130050380. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Olanzapine Olanzapine : Week 1- 5 mg BID Week 2- 5 mg am and 10 mg pm Weeks 3-6 10 mg am and 10 mg pm |
|
|
| Primary | Change in Negative Symptoms by Treatment Assignment | The Scale for the Assessment of Negative Symptoms (SANS) total score, minus the global items, inappropriate affect, poverty of content of speech, and attention items, used to measure negative symptoms. Mean SANS total score by treatment and week. SANS total score range = 0-85. Higher scores indicate more severe negative symptoms. | Participants completing SANS assessment. | Posted | Mean | Standard Deviation | units on a scale | Baseline and Follow-Up |
|
|
|
| Primary | The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) | The RBANS is a brief, individually administered test designed to evaluate neuropsychological status of adults, ages 20-89. The 12 subtests measure attention, language, visuospatial/constructional abilities, and immediate and delayed memory. The raw scores from the subtests are scaled together to create index scores, and these are summed for conversion to a total scale score. Higher score equals a better outcome. The total index score range for the RBANS is 40-160. | Participants completing cognitive testing. | Posted | Mean | Standard Deviation | units on a scale | Baseline and Follow-Up |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | Olanzapine | Olanzapine Olanzapine : Week 1- 5 mg BID Week 2- 5 mg am and 10 mg pm Weeks 3-6 10 mg am and 10 mg pm | 0 | 8 | 0 | 8 |
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| D001552 |
| Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Follow-Up (Phase 4/Week 1) |
|
|