Cognitive Effects of Nimodipine in Patients With Schizophrenia

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizo Affective Disorder
• Intervention / Treatment: Drug: Nimodipine; Drug: Placebo oral capsule

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nimodipine; One 60mg capsule of nimodipine on first or second study visit	Drug: Nimodipine; Subject will receive two 30mg capsules of nimodipine during study visit.; Other Names: Nymalize
Placebo Comparator: Placebo; One placebo capsule on first or second study visit	Drug: Placebo oral capsule; Two coconut oil capsules that mimic the size and color of the nimodipine capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	between 30 min and 1 hour after dose
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)	approximately an hour after dose
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).	approximately an hour after dose
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.	approximately an hour after dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	during 2-3 hour study visit
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.	during 2-3 hour study visit

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Kristin Bigos, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2018
• Primary Completion (Actual): May 12, 2023
• Study Completion (Actual): May 12, 2023

Study Registration Dates

• First Submitted: August 6, 2018
• First Submitted That Met QC Criteria: September 12, 2018
• First Posted (Actual): September 14, 2018

Study Record Updates

• Last Update Posted (Actual): June 23, 2023
• Last Update Submitted That Met QC Criteria: June 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mood Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Nimodipine
• Other Study ID Numbers: IRB00168634

Drug and device information, study documents

• 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