Understanding the effects of the PDE4 inhibitor Roflumilast on Memory
Research type
Research Study
Full title
A RANDOMISED, DOUBLE BLIND, PLACEBO CONTROLLED, TWO WAY CROSSOVER STUDY TO EVALUATE THE EFFECTS OF THE PDE4 INHIBITOR ROFLUMILAST ON MEMORY WHEN GIVEN TO PATIENTS WITH SCHIZOPHRENIA.
IRAS ID
271620
Contact name
Fiona Patrick
Contact email
Clinicaltrials.gov Identifier
to be provided once registered, The Open Science Framework [OSF.io]
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Memory processing is one of the most consistently reported cognitive deficits in schizophrenia and has the largest deficits. The strong association of memory deficits with functional outcomes in comparison to other aspects of cognition has been replicated a number of times, and evidence suggests it may be strongest with verbal episodic memory (memory of autobiographical events such as times, places, associated emotions, and other contextual who, what, when, where, why knowledge). Deficiencies in these areas may prevent patients from attaining optimal adaptation and hence act as "neurocognitive rate-limiting factors". Accordingly, cognitive improvements, particularly towards memory, are priority therapeutic targets for patients with schizophrenia.
The development and licensing of new drugs is expensive and slow so the potential to use existing compounds developed for other disorders to test proof of concept questions is attractive. We recently conducted a study using an existing PDE4 inhibitor and showed improved episodic memory in a small group of patients with schizophrenia (approved by NRES Committee London - Surrey Borders ; ref: 12/LO/1204). We propose to build on that research using Rofumilast, which is a compound that is already available for treatment of a common breathing disorder (COPD). In addition, we hope to establish which aspects of episodic memory are most sensitive to the drug. This will provide preliminary indication of which specific memory impairments in schizophrenia may be targeted by the PDE4 inhibition mechanism.
In this study we plan to recruit almost twice as many patients and utilise a broader battery of memory tests to specify the areas of construct sensitivity more comprehensively and explore the everyday functional capacity measures that can be used in future trials.
The study is a placebo-controlled, double-blind, cross-over design study. Patients with a diagnosis of schizophrenia and on a stable dose of an antipsychotic will attend for a screening visit, followed by two eight-day study treatment periods (Days 1-8). Patients will receive an oral daily dose 250μg roflumilast or placebo during each study period. Patients will attend the clinic on days 1 and 8 when they will receive a battery of memory tests before first dose and after last dose of each period. On Days 2-7 they will take a dose of 250μg roflumilast or matched placebo each morning at home and may also carry out an optional online language learning task.REC name
London - London Bridge Research Ethics Committee
REC reference
20/LO/0171
Date of REC Opinion
20 Apr 2020
REC opinion
Further Information Favourable Opinion