Back to resultsCognitive Effects of Nimodipine in Patients With Schizophrenia
Primary Purpose
Schizophrenia, Schizo Affective Disorder
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nimodipine
Placebo oral capsule
Sponsored by
About this trial
This is an interventional other trial for Schizophrenia
Eligibility Criteria
Inclusion Criteria:
- This study will recruit patients with schizophrenia and/or schizoaffective disorder
Exclusion Criteria:
- past or current neurological disorder (including stroke, brain tumor, epilepsy, Alzheimer's, Parkinson's or Huntington's disease)
- uncontrolled medical disorder
- current or past hypotension
- head trauma with loss of consciousness in the last year or any evidence of functional impairment due to and persisting after head trauma
- positive pregnancy test, or currently breast feeding
- having an adverse reaction to nimodipine, or other calcium channel blocker
Sites / Locations
- Johns Hopkins Bayview Medical Center
- Johns Hopkins University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Nimodipine
Placebo
Arm Description
One 60mg capsule of nimodipine on first or second study visit
One placebo capsule on first or second study visit
Outcomes
Primary Outcome Measures
Brain activity as assessed by BOLD fMRI
participants will complete an MRI scan to link brain activity with cognitive performance. Measures will be recorded in Arbitrary units.
Changes in Visual Learning and Memory Score
Participants will complete the Brief Visuospatial Memory Task - Revised (BVMT-R) before and after administration of drug or placebo to determine the effect of nimodipine on visuospatial memory in patients with schizophrenia. Scores range from 0 to 60, with higher values indicating better performance. Administration takes approximately 45 minutes to complete (including a 25 minute delay)
Changes in Auditory Learning and Memory Score
During each study visit, participants will complete the Hopkins Verbal Learning Task - Revised (HVLT-R) before and after administration of drug or placebo to determine the effect of nimodipine on verbal learning and memory in patients with schizophrenia. Scores range from 0 to 60, with higher values indicating better performance. Administration takes approximately 35 minutes to complete (including a 20-25 minute delay).
Changes in Global Neurocognitive effect as assessed by the Global Neurocognitive Assessment (GNA)
During each study visit, participants will complete the Global Neurocognitive Assessment (GNA) before and after administration of drug or placebo to determine the effect of nimodipine on a range of neurocognitive measures in patients with schizophrenia. The GNA contains 10 items with varying score ranges. Higher scores indicate better performance.
Secondary Outcome Measures
Effect of CACNA1C genotype on cognitive performance measures
The CACNA1C risk-associated SNP (rs1006737) will be tested using a linear regression (with copy of A alleles) with each cognitive domain score to determine if CACNA1C genetics impact response to nimodipine.
Broader genetic associations with cognitive performance
Genetic data will be used more broadly to include testing of the effects of genetic variation including but not limited to schizophrenia, cognition, behavior, and drug metabolism.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03671525
Brief Title
Cognitive Effects of Nimodipine in Patients With Schizophrenia
Official Title
Cognitive Effects of Nimodipine in Patients With Schizophrenia
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
October 5, 2018 (Actual)
Primary Completion Date
May 12, 2023 (Actual)
Study Completion Date
May 12, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
Brief Summary
This study aims to evaluate the acute effects of nimodipine on cognitive performance in patients with schizophrenia using a battery of cognitive assessments.The subjects will also complete a 30-minute structural and functional MRI scan, with the goal of linking brain activity with working memory performance. Investigators predict that the performance increase induced by nimodipine will be greater in subjects who carry the A allele for the Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C) risk single nucleotide polymorphism (SNP) (rs1006737) in comparison to the response of G carriers.
Detailed Description
The main cognitive task of interest in this study is the N-back task because of the observed attenuation of prefrontal and parietal cortical activity after nimodipine administration in healthy subjects. Investigators hypothesize that acute nimodipine administration will improve cortical activation, which will lead to improved cognitive performance. The current study will provide insight whether nimodipine or another calcium channel blocker could be used as a treatment approach to alleviate cognitive deficits in patients with schizophrenia.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizo Affective Disorder
7. Study Design
Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nimodipine
Arm Type
Experimental
Arm Description
One 60mg capsule of nimodipine on first or second study visit
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
One placebo capsule on first or second study visit
Intervention Type
Drug
Intervention Name(s)
Nimodipine
Other Intervention Name(s)
Nymalize
Intervention Description
Subject will receive two 30mg capsules of nimodipine during study visit.
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
Two coconut oil capsules that mimic the size and color of the nimodipine capsules
Primary Outcome Measure Information:
Title
Brain activity as assessed by BOLD fMRI
Description
participants will complete an MRI scan to link brain activity with cognitive performance. Measures will be recorded in Arbitrary units.
Time Frame
between 30 min and 1 hour after dose
Title
Changes in Visual Learning and Memory Score
Description
Participants will complete the Brief Visuospatial Memory Task - Revised (BVMT-R) before and after administration of drug or placebo to determine the effect of nimodipine on visuospatial memory in patients with schizophrenia. Scores range from 0 to 60, with higher values indicating better performance. Administration takes approximately 45 minutes to complete (including a 25 minute delay)
Time Frame
approximately an hour after dose
Title
Changes in Auditory Learning and Memory Score
Description
During each study visit, participants will complete the Hopkins Verbal Learning Task - Revised (HVLT-R) before and after administration of drug or placebo to determine the effect of nimodipine on verbal learning and memory in patients with schizophrenia. Scores range from 0 to 60, with higher values indicating better performance. Administration takes approximately 35 minutes to complete (including a 20-25 minute delay).
Time Frame
approximately an hour after dose
Title
Changes in Global Neurocognitive effect as assessed by the Global Neurocognitive Assessment (GNA)
Description
During each study visit, participants will complete the Global Neurocognitive Assessment (GNA) before and after administration of drug or placebo to determine the effect of nimodipine on a range of neurocognitive measures in patients with schizophrenia. The GNA contains 10 items with varying score ranges. Higher scores indicate better performance.
Time Frame
approximately an hour after dose
Secondary Outcome Measure Information:
Title
Effect of CACNA1C genotype on cognitive performance measures
Description
The CACNA1C risk-associated SNP (rs1006737) will be tested using a linear regression (with copy of A alleles) with each cognitive domain score to determine if CACNA1C genetics impact response to nimodipine.
Time Frame
during 2-3 hour study visit
Title
Broader genetic associations with cognitive performance
Description
Genetic data will be used more broadly to include testing of the effects of genetic variation including but not limited to schizophrenia, cognition, behavior, and drug metabolism.
Time Frame
during 2-3 hour study visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
This study will recruit patients with schizophrenia and/or schizoaffective disorder
Exclusion Criteria:
past or current neurological disorder (including stroke, brain tumor, epilepsy, Alzheimer's, Parkinson's or Huntington's disease)
uncontrolled medical disorder
current or past hypotension
head trauma with loss of consciousness in the last year or any evidence of functional impairment due to and persisting after head trauma
positive pregnancy test, or currently breast feeding
having an adverse reaction to nimodipine, or other calcium channel blocker
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristin Bigos, PhD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Bayview Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
12. IPD Sharing Statement
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Cognitive Effects of Nimodipine in Patients With Schizophrenia
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