Clinical Trial of Dipyridamole in Schizophrenia

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Completed
• CT.gov ID: NCT00349973
• Collaborator: (none)
• Enrollment: 29
• Location: 1
• Arms: 2
• Duration (Months): 124
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder	Drug: Dipyridamole; Other: Olanzapine	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Clinical Trial of Dipyridamole in Schizophrenia
• Study Start Date: May 1, 2001
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Dipyridamole	Drug: 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
Active Comparator: 2 Olanzapine	Other: 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

Outcome Measures

Primary Outcome Measures

1. Change in Positive Symptoms by Treatment Assignment [Baseline and follow-up]

   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.

2. Change in Negative Symptoms by Treatment Assignment [Baseline and Follow-Up]

   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.

3. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [Baseline and Follow-Up]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maryland Psychiatric Research Center	Baltimore	Maryland	United States	21228

Sponsors and Collaborators

• University of Maryland, Baltimore

Investigators

• Study Director: Ikwunga Wonodi, MD, Maryland Pschiatric Research Center, University of Maryland School of Medicine
• Principal Investigator: Gunvant K Thaker, MD, University of Maryland, College Park

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Maryland Psychiatric Research Center

Publications

None provided.

• Responsible Party: L. Elliot Hong, Associate Professor, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT00349973
• Other Study ID Numbers: HP-00043347
• First Posted: Jul 10, 2006
• Last Update Posted: Nov 4, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by L. Elliot Hong, Associate Professor, University of Maryland, Baltimore: Schizophrenia; Positive symptoms; Negative symptoms; Cognitive deficits
• Additional relevant MeSH terms: Disease; Schizophrenia; Psychotic Disorders; Dipyridamole; Olanzapine

Study Results

Participant Flow

Pre-assignment Detail	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).

Arm/Group Title	Dipyridamole	Olanzapine
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	12	8
COMPLETED	8	5
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	Dipyridamole	Olanzapine	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	12	8	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	8 100%	20 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	5 41.7%	4 50%	9 45%
Male	7 58.3%	4 50%	11 55%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 50%	4 50%	10 50%
White	6 50%	4 50%	10 50%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change in Positive Symptoms by Treatment Assignment
Description	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.
Time Frame	Baseline and follow-up

Outcome Measure Data

Analysis Population Description

Participants completing the BPRS assessment.

Arm/Group Title	Dipyridamole	Olanzapine
Arm/Group Description	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	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
Measure Participants	9	5
Baseline - Somatic Concern	2.222 (1.716)	1.400 (0.548)
Follow-Up - Somatic Concern	1.60 (1.34)	1.00 (0.00)
Baseline - Conceptual Disorganization	2.667 (1.225)	2.600 (0.894)
Follow-Up - Conceptual Disorganization	2.00 (1.41)	2.00 (1.41)
Baseline - Hostility	1.222 (0.667)	1.200 (0.447)
Follow-Up - Hostility	1.00 (0.00)	2.00 (1.41)
Baseline - Suspiciousness	4.11 (1.54)	3.40 (1.82)
Follow-Up - Suspiciousness	3.000 (1.581)	1.500 (0.707)
Baseline - Hallucination	2.67 (2.12)	3.80 (1.30)
Follow-Up - Hallucination	2.600 (2.191)	2.500 (0.707)
Baseline - Unusual Thought Content	3.111 (1.167)	3.400 (0.894)
Follow-Up - Unusual Thought Content	2.800 (2.168)	1.500 (0.707)

2. Primary Outcome

Title	Change in Negative Symptoms by Treatment Assignment
Description	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.
Time Frame	Baseline and Follow-Up

Outcome Measure Data

Analysis Population Description

Participants completing SANS assessment.

Arm/Group Title	Dipyridamole	Olanzapine
Arm/Group Description	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	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
Measure Participants	9	5
Baseline (Phase 1/Week 1)	23.3 (14.7)	25.6 (20.5)
Follow-Up (Phase 4/Week 1)	25.8 (10.7)	27.0 (29.7)

3. Primary Outcome

Title	The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Description	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.
Time Frame	Baseline and Follow-Up

Outcome Measure Data

Analysis Population Description

Participants completing cognitive testing.

Arm/Group Title	Dipyridamole	Olanzapine
Arm/Group Description	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	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
Measure Participants	5	2
Baseline (Phase 1/Week 1)	73.00 (15.41)	59.00 (1.41)
Follow-Up (Phase 3/Week 6)	77.40 (14.83)	65.00 (2.83)

Adverse Events

Arm/Group Title	Dipyridamole		Olanzapine
Arm/Group Description	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		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
All Cause Mortality
	Dipyridamole		Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dipyridamole		Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Dipyridamole		Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.