Dose Finding Study of Nimodipine for the Treatment of Progranulin Insufficiency From GRN Gene Mutations

2015-02-11 20:08:23 | BioPortfolio


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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label


Progranulin Mutation Carriers




UCSF Memory and Aging Center
San Francisco
United States




University of California, San Francisco

Results (where available)

View Results


Published on BioPortfolio: 2015-02-11T20:08:23-0500

Clinical Trials [555 Associated Clinical Trials listed on BioPortfolio]

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...

Validation of Progranulin as a Biomarker for Sepsis

Progranulin blood concentrations in patients with sepsis will be analysed in relation to disease status in order to validate progranulin as a biomarker for sepsis. Patients undergoing card...

Impact of Testing Positive for the BRCA1 or BRCA2 Mutation in Young Women Who Are BRCA1 or BRCA2 Mutation Carriers

RATIONALE: Gathering information from women who are BRCA1 or BRCA2 mutation carriers may help doctors learn how they manage cancer risk and meet the challenges of young adulthood. PURPOSE...

High Order Spectral Analysis of Local Field Potential Data on a Subgroup of Parkinson's Disease Patients Who Are Carriers of Mutations in the Glucocerebrosidase (GBA) Gene Undergoing DBS Electrode Placement

We aim to study a specific group of PD patients, carriers of mutations in the glucocerebrosidase (GBA) gene, which is the most common genetic risk factor for PD and is a harbinger of aggre...

Decoding Presymptomatic White Matter Changes in Huntington Disease

WIN-HD is a monocentric longitudinal study comparing premanifest Huntingtin (HTT) mutation carriers and non HTT mutation carriers to determine that white-matter atrophy occurs far earlier ...

PubMed Articles [3166 Associated PubMed Articles listed on BioPortfolio]

Gait asymmetry in glucocerebrosidase mutation carriers with Parkinson's disease.

GBA mutation carriers with PD (PD-GBA) are at higher risk of cognitive decline, but there is limited data regarding whether there are differences in gait dysfunction between GBA mutation and non-mutat...

Breast cancer surveillance for BRCA1/2 mutation carriers - is "early detection" early enough?

Annual MRI screening is associated with a significant reduction in advanced-stage breast cancer diagnosis in BRCA1/2 mutation carriers. The impact that early detection has on subsequent oncological tr...

Nimodipine pharmacokinetics after intraventricular injection of sustained-release nimodipine for subarachnoid hemorrhage.

The objective of this study was to measure the concentration of nimodipine in CSF and plasma after intraventricular injection of a sustained-release formulation of nimodipine (EG-1962) in patients wit...

Tracking white matter degeneration in asymptomatic and symptomatic MAPT mutation carriers.

Our aim was to investigate the patterns and trajectories of white matter (WM) diffusion abnormalities in microtubule-associated protein tau (MAPT) mutations carriers. We studied 22 MAPT mutation carri...

Chitosan nanoparticles release nimodipine in response to tissue acidosis to attenuate spreading depolarization evoked during forebrain ischemia.

Stroke is an important cause of mortality and disability. Treatment options are limited, therefore the progress in this regard is urgently needed. Nimodipine, an L-type voltage-gated calcium channel a...

Medical and Biotech [MESH] Definitions

Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.

A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.

Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).

A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.

Concept which describes the incremental effects of MUTATION in living organisms.

More From BioPortfolio on "Dose Finding Study of Nimodipine for the Treatment of Progranulin Insufficiency From GRN Gene Mutations"

Quick Search

Relevant Topics

Alzheimer's Disease
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase  'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...

Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Searches Linking to this Trial