Cognitive Effects of Nimodipine in Patients With Schizophrenia

NCT03671525 | Completed Early Phase 1 FDA Drug

• 1 other identifier: IRB00168634
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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.

Conditions

Schizophrenia; Schizo Affective Disorder

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• Effect of CACNA1C genotype on cognitive performance measures

  during 2-3 hour study visit

• Broader genetic associations with cognitive performance

  during 2-3 hour study visit

Study Arms (2)

Nimodipine

EXPERIMENTAL

One 60mg capsule of nimodipine on first or second study visit

Drug: Nimodipine

Placebo

PLACEBO COMPARATOR

One placebo capsule on first or second study visit

Drug: Placebo oral capsule

Interventions

Nimodipine DRUG

Subject will receive two 30mg capsules of nimodipine during study visit.

Also known as: Nymalize

Nimodipine

Placebo oral capsule DRUG

Two coconut oil capsules that mimic the size and color of the nimodipine capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• This study will recruit patients with schizophrenia and/or schizoaffective disorder

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (2)

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Nimodipine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nicotinic Acids

Study Officials

• Kristin Bigos, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2018
• First Posted: September 14, 2018
• Study Start: October 5, 2018
• Primary Completion: May 12, 2023
• Study Completion: May 12, 2023
• Last Updated: June 23, 2023

Record last verified: 2023-05

Locations

US (2)