Clinical trial NCT00349973: Clinical Trial of Dipyridamole in Schizophrenia
Official title: Clinical Trial of Dipyridamole in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Schizoaffective Disorder
Schizophreniform Disorder
Keywords: Schizophrenia
Positive symptoms
Negative symptoms
Cognitive deficits
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
First posted: 2006-07-10
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Subjects between ages 18-65, both males and nonpregnant females (on birth control) Diagnosis of schizophrenia, schizoaffective or schizophreniform disorder Ability to give written informed consent Total BPRS score \> 27 Psychosis subscale scores \> 7

Exclusion Criteria:

* Patients with coagulative disorders, bleeding diathesis or currently on anticoagulants, and patients with major medical illnesses (including hypertension, angina, and cardiovascular diseases) or an abnormal baseline ECG.

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

Primary outcomes:
measure: Change in Positive Symptoms by Treatment Assignment
timeFrame: Baseline and follow-up
measure: Change in Negative Symptoms by Treatment Assignment
timeFrame: Baseline and Follow-Up
measure: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
timeFrame: Baseline and Follow-Up
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Maryland Psychiatric Research Center
state: Maryland
Study officials:
affiliation: Maryland Pschiatric Research Center, University of Maryland School of Medicine
name: Ikwunga Wonodi, MD
role: STUDY_DIRECTOR
affiliation: University of Maryland, College Park
name: Gunvant K Thaker, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.