Roflumilast to Treat Cognitive Sequela After Stroke
Condition: Cerebrovascular Disorders; Memory; Functional Recovery; Drug Intervention
MeSH terms: Cerebrovascular Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      The aim of the current project is to validate the effects of chronic rolflumilast treatment
      (12 weeks) on cognitive functions (i.e. episodic memory) by means of behavioral tasks, in
      people suffering from cognitive impairments at least 1 year after stroke. Secondarily, the
      effects of roflumilast on daily activities and well-being will be assessed.
    

Detailed description: 
      Rationale: In the Netherlands there are about 400.000 people who suffer from long-term
      consequences of a stroke. In the first months, spontaneous neurological recovery can take
      place, but there is hardly any functional recovery found one year after a stroke. About 40%
      of these patients indicate that one of the greatest problems they are facing is the
      impairment in cognitive functions, which also seems to be predictive for the disease outcome.
      Currently, the main focus of helping these patients is helping them to cope with and adapt to
      the new situation. There is a great medical need to actually improve cognitive functions in
      people that still suffer from persistent cognitive impairments one year after a stroke.

      Animal studies have shown that the enzyme phosphodiesterase type 4 (PDE4) plays an important
      role in the brain, as it has been shown to be critically linked to neuronal plasticity.
      Although animal studies may not always predict effects in humans, there is a strong case that
      PDE4 inhibition may also work in humans. Researchers from Maastricht University, and others,
      have shown that the PDE4 inhibitor roflumilast improved memory performance in old healthy
      participants and in schizophrenic patients. This is a proof of concept that PDE4 inhibition
      can improve memory performance in humans. A logical next step is to test if roflumilast can
      improve cognitive functioning and daily life activities in people suffering from cognitive
      problems more than one year after stroke.

      Objective: The objective is to validate the effects of chronic roflumilast treatment on
      cognitive function (i.e. episodic memory) by means of behavioral tasks, in people suffering
      from cognitive impairments at least 1 year after stroke. Secondary, the effects of
      roflumilast on daily activities and well-being will be assessed.

      Study design: The first phase of study will be conducted according to a double-blind,
      randomized placebo-controlled, between-subjects design. In a second phase, the placebo group
      will be given the opportunity to receive roflumilast. This is an open label design.

      Study population: 100 female and male, people (41-70 years old) suffering from cognitive
      complaints 1 year after stroke will be recruited via advertisements via social media and via
      local caretaking organizations (e.g., SGL, Adelante).

      Intervention: The study will consist of 2 arms (N = 50 per arm): placebo and 100 μg
      roflumilast. The duration of treatment is planned for 3 months and participants will be
      tested at baseline, after 1.5 months, after 3 months. The participants will also do daily
      computer games to stimulate their brain function. The roflumilast group will be tested 3
      months treatment stopped to test if the effects last after treatment is discontinued. After
      the end of the 3 months-intervention period, the participants of the placebo group will be
      identified and they will be asked whether they would like to take roflumilast for a 3-month
      period. This will give information as to the roflumilast effects in an open label setting.
      Moreover, this gives the participants in the placebo group the opportunity to receive the
      active treatment (if they wish)."
    

Intervention name(s): Roflumilast Oral Tablet
Intervention type(s): Drug
Intervention description(s): Once daily for 12 weeks
Other intervention name(s): EU: Daxas; US: Daliresp; PDE4 inhibitor
Intervention MeSH terms: Phosphodiesterase 4 Inhibitors
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Between subjects, double blind, placebo-controlled, randomized
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Cerebrovascular Disorders; Plasticity; Phosphodiesterase inhibitor; Memory; Roflumilast