Lead Investigator: Amit Etkin, Alto Neuroscience
Title of Proposal Research: Understanding individual differences in response to roflumilast in schizophrenia
Vivli Data Request: 8765
Funding Source: None
Potential Conflicts of Interest: Dr. Etkin reports: Full-time employee of Alto Neuroscience-work being proposed is part of the job responsibilities for Alto. Alto is supporting this project. – Equity in Mindstrong Health and Akili Interactive for unrelated work. Receives salary and has stock in Alto. Should any conflict of interest arise that is relevant to the sponsors of the study, this will be shared with Vivli, and steps will be taken to ensure that the conflict does not impact analyses.
Dr. Cooper reports: Full-time employee of Alto Neuroscience-work being proposed is part of the job responsibilities for Alto. Alto is supporting this project. Receives salary and has stock in Alto. Should any conflict of interest arise that is relevant to the sponsors of the study, this will be shared with Vivli, and steps will be taken to ensure that the conflict does not impact analyses.
Dr. Jordan reports: Full-time employee of Alto Neuroscience-work being proposed is part of the job responsibilities for Alto. Alto is supporting this project. Receives salary and has stock in Alto. Should any conflict of interest arise that is relevant to the sponsors of the study, this will be shared with Vivli, and steps will be taken to ensure that the conflict does not impact analyses.
Dr. Wu reports: Full-time employee of Alto Neuroscience-work being proposed is part of the job responsibilities for Alto. Alto is supporting this project. Receives salary and has stock in Alto. Should any conflict of interest arise that is relevant to the sponsors of the study, this will be shared with Vivli, and steps will be taken to ensure that the conflict does not impact analyses.
Summary of the Proposed Research:
Schizophrenia is a disorder that affects approximately 24 million people worldwide (approximately 0.30% of the population), with age of onset typically in late adolescence and early adulthood. It is associated with considerable functional impairment and early mortality compared to the rest of the population. There are severe, prominent impairments with cognition (i.e. the mechanics of thinking) in this population, which include problems with attention, memory and the ability to make decisions.
One drug mechanism that may help cognition in schizophrenia is through the inhibition of the phosphodiesterase 4 enzyme (PDE4). This enzyme breaks down molecules in nerve cells that signal when the nerve cell has gotten important information, and are as a consequence important players in memory formation. By inhibiting the breakdown of these molecules, PDE4 inhibitors can enhance cognition. One such inhibitor is roflumilast, which was examined in this exploratory study in a short-term treatment of patients with schizophrenia.
The prior investigation of roflumilast on schizophrenia examined whether roflumilast attenuated cognitive impairment using a three-period crossover design in which patients were randomly assigned to receive roflumilast (100 µg or 250 µg) and placebo in a pre-specified order. The study consisted of three 8-day treatment periods (100 µg or 250 µg of roflumilast, or placebo) separated by a period of at least 14 days. The proposed research is exploratory and seeks to expand on their findings by exploring the impact of patient attributes (e.g., baseline cognitive performance, baseline electrical responses of the brain to sensory stimuli) prior to the initiation of treatment on the prediction of cognitive impact with roflumilast. This research is intended to be hypothesis-generating, in that findings may inform hypotheses for future studies.
Requested Studies:
A Randomized, Double-Blind, Placebo Controlled, 3-period, Proof of Mechanism, Cross-Over Study of Roflumilast Administered up to Steady State to Evaluate the Effects of Add-on Roflumilast to Second Generation Antipsychotics on Cognitive Impairment as Well as Brain Imaging (ie, fMRI) and Electrical Activity (ie, EEG) Changes Observed in Subjects With Stable Schizophrenia
Data Contributor: AstraZeneca
Study ID: NCT02079844
Sponsor ID: ROF-SCHZ_106