An Open Label Dose Finding Study of Nimodipine for the Treatment of Frontotemporal Dementia Due to Progranulin Insufficiency From GRN Gene Mutations

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Investigator: Adam L. Boxer, MD, PhD
Sponsor: Bluefield Project to Cure Frontotemporal Dementia (FTD)

Location(s): United States

Description

The purpose of this study is to determine the maximum tolerated dose of nimodipine as well as the safety and tolerability of oral nimodipine in progranulin mutation carriers in preparation for longer term efficacy studies in patients with frontotemporal dementia due to progranulin gene mutations.

8 people with a GRN gene mutation will be given escalating doses of oral nimodipine for four weeks, followed by the maximally tolerated dose for four weeks. To maximize enrollment, the trial will enroll both symptomatic and asymptomatic GRN mutation carriers. The trial will include a four week, dose-escalation phase followed by 1-month maintenance phase, and a 1-week taper. Assessments at the study site will take place prior to starting nimodipine, each week the dose is increased (weeks 1-5), after 4 weeks of maintenance dose, and 2 weeks after completion of the study. These will include blood chemistry tests, ECGs, and blood pressure. Both dose escalation and maintenance will focus on safety and tolerability of nimodipine treatment in this population as well as plasma progranulin levels as a biomarker outcome. The trial will incorporate a variety of other fluid biomarker (blood and CSF) and imaging assessments to determine which will be most sensitive to nimodipine pharmacodynamic effects in this population.