Roflumilast and Cognition (EEGrofl)

Effects of Roflumilast on Cognition in Healthy Adults: a Behaviour-EEG Study

The aim of the current project is to validate PDE4 inhibitors as a target for cognition enhancers (proof-of-concept) using a translational behaviour-EEG approach. The project will demonstrate whether memory, but also attention, information processing or executive function improves with the PDE4 inhibitor roflumilast in healthy humans.

Study Overview

• Status: Completed
• Conditions: Dementia
• Intervention / Treatment: Drug: roflumilast (EU: Daxas, USA: Daliresp); Drug: roflumilast; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6200 MD
      • Maastricht University, Faculty of Psychology and Neuroscience

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 to 35 years of age
• Healthy (i.e. absence of all exclusion criteria), normal static binocular acuity (corrected or uncorrected),
• Body mass index between 18.5 and 30
• Willingness to sign an informed consent.
• Positive evaluation on the memory screening

Exclusion Criteria:

• History of cardiac, hepatic, renal, pulmonary, neurological, gastrointestinal, haematological, or psychiatric illness
• First-degree relative with psychiatric disorder (in particular major depressive disorder and suicidality)
• Excessive drinking (>20 glasses of alcohol containing beverages per week)
• Pregnancy or lactation
• Use of chronic medication other than oral contraceptives
• Use of recreational drugs in the 2 weeks preceding participation
• Smoking
• Orthostatic hypotension
• Lactose intolerance
• Sensory or motor deficits which could reasonably be expected to affect test performance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: roflumilast; Acute intervention: 1 time each dose (100ug, 300ug, 1000ug, placebo). Capsulated.; Other Names: Daliresp; Daxas; PDE4-inhibitor; Drug: Placebo; Acute intervention: single administration, capsulated form.
Experimental: roflumilast 100ug	Drug: roflumilast (EU: Daxas, USA: Daliresp); Acute intervention: 1 time each dose on different days. Capsulated; Drug: roflumilast; Acute intervention: 1 time each dose (100ug, 300ug, 1000ug, placebo). Capsulated.; Other Names: Daliresp; Daxas; PDE4-inhibitor
Experimental: roflumilast 300ug	Drug: roflumilast (EU: Daxas, USA: Daliresp); Acute intervention: 1 time each dose on different days. Capsulated; Drug: roflumilast; Acute intervention: 1 time each dose (100ug, 300ug, 1000ug, placebo). Capsulated.; Other Names: Daliresp; Daxas; PDE4-inhibitor
Experimental: roflumilast1000ug	Drug: roflumilast (EU: Daxas, USA: Daliresp); Acute intervention: 1 time each dose on different days. Capsulated; Drug: roflumilast; Acute intervention: 1 time each dose (100ug, 300ug, 1000ug, placebo). Capsulated.; Other Names: Daliresp; Daxas; PDE4-inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of words remembered on Verbal learning task	30 monosyllable words will be displayed on a computer screen. Immediately after the presentation and after 45 minutes, subjects will be asked to report as much words as they remember. In addition, a recognition trial is conducted. Here, 30 words will be presented; 15 new words and 15 from the original list. Subjects have to indicate whether the word is old or new.	1hr after drug intake

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
• Investigators: Study Director: Jos H. Prickaerts, PhD, Maastricht University

Publications and helpful links

General Publications

• Heckman PRA, Van Duinen MA, Blokland A, Uz T, Prickaerts J, Sambeth A. Acute administration of roflumilast enhances sensory gating in healthy young humans in a randomized trial. Psychopharmacology (Berl). 2018 Jan;235(1):301-308. doi: 10.1007/s00213-017-4770-y. Epub 2017 Nov 3.
• Van Duinen MA, Sambeth A, Heckman PRA, Smit S, Tsai M, Lahu G, Uz T, Blokland A, Prickaerts J. Acute administration of roflumilast enhances immediate recall of verbal word memory in healthy young adults. Neuropharmacology. 2018 Mar 15;131:31-38. doi: 10.1016/j.neuropharm.2017.12.019. Epub 2017 Dec 11.

Helpful Links

• Published main data
• Published sensory gating data

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: June 27, 2011
• First Submitted That Met QC Criteria: September 13, 2011
• First Posted (Estimate): September 14, 2011

Study Record Updates

• Last Update Posted (Actual): January 2, 2020
• Last Update Submitted That Met QC Criteria: December 30, 2019
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Dementia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors
• Other Study ID Numbers: METC11-3-035; ZonMw (the Netherlands) (Other Grant/Funding Number: 95110091); 2011-002070-23 (EudraCT Number)