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.
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome measure: The delayed recall performance in the Verbal Word
Learning Task is used as the primary outcome measure since our previous study
with roflumilast showed effects in this task.
Secondary outcome
Secondary outcome measures: Cognitive performance: the total score of the
Rivermead Behavioural Memory Test, Everyday Memory Questionnaire-Revised,
Digit-Symbol Substitution Test, Trail Making Test, reaction time test (simple
reaction time, movement time).
Mood and well-being: Utrechtse Schaal voor Evaluatie van
Revalidatie-Participatie, and the total mood score of the Hospital Anxiety and
Depression Scale questionnaire.
Background summary
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.
We, 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.
Study 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.
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.
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
in addition, all participants will train their cognitive functions at home
(Cogstate, computerized tests) 5x a week, 15 minutes per day. This is to
simulate the working of the pill (i.e. improving brain plasticity).
Study burden and risks
The intervention consists of taking 1 pill (roflumilast or placebo), daily
during three months.
The most common side-effects described for roflumilast are: weight loss,
headache, nausea, diarrhoea, abdominal pain, insomnia, and dizziness. The risks
of experiencing side effects are considered low.
In addition, during these three months, all participants will train their
cognitive functions at home (Cogstate, computerized tests) 5x a week, 15
minutes per day
Assessment time invested by the patient will be approximately 8.5 hours in
total: an assessment for eligibility (medical evaluation) (1 hour); baseline
test session (90 minutes), acute test session after first single dose (90
minutes), test session after 1.5 months (90 minutes), test session after
completion of 3 months (90 minutes) and a test session 3 months post-completion
for follow up (90 minutes)
during the study participants need to obey certain rules:
starting a week before testing, participants cannot take drugs or medicines
that may influence the working of roflumilast.
24 hours before testing, and on the testday, participants cannot consume
alcohol. On a testday they are asked not to consume caffeinated drinks (coffee,
cola) and not to smoke. In addition participants are asked to take care of a
normal night's rest the night before a test day.
Finally, during the study, participants cannot take part in another biomedical
study.
Universiteitssingel 40
Maastricht 6229 ER
NL
Universiteitssingel 40
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
-41 to 70 years of age;
-willingness to sign an IC;
-Objective cognitive complaint: memory performance on the delayed recall in the
15 words VWLT below the normative score (corrected for education, sex and age)
(see Van der Elst, van Boxtel, van Breukelen, & Jolles, 2005).
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participating in this study: Normal Pressure Hydrocephalus (NPH), Morbus
Huntington, Parkinson's disease, HIV/AIDS and Hepatitis B and C, recent
Transient Ischemic Attack (TIA), COPD Gold 3 and 4, history of schizophrenia,
bipolar disorder or psychotic symptoms not otherwise specified or previous
treatment for these diseases (lifetime), current affective disorder (i.e.
anxiety or major depression), cognitive problems due to alcohol abuse, brain
tumor, epilepsy, encephalitis or lack of capacity to consent to participation.
Other exclusion criteria are current treatment with (or illicit use of)
cannabis, opiates, benzodiazepines, Methylenedioxymethamphetamine (MDMA) and
cocaine. Roflumilast is contraindicated in patients with moderate to severe
liver impairment, accordingly patients with moderate or major liver impairments
will be excluded (e.g. Child-Pugh B and C). Use of medication showing strong
inhibition of either CYP3A4 (e.g. clarithromycin, antihistamines) or CYP1A2
(e.g. fluvoxamine, ciprofloxacin and other fluoroquinolones) is also an
exclusion criterion because of interference with roflumilast metabolism
resulting in reduced therapeutic effectiveness of roflumilast. Individuals with
rare hereditary problems of galactose intolerance, Lapp lactase deficiency or
glucose-galactose malabsorption will be excluded, as both the placebo and
roflumilast contain lactose monohydrate. Additionally, during the period of the
present study, participants are not allowed to participate in other drug
trials.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-003768-16-NL |
| ClinicalTrials.gov | NCT04854811 |
| CCMO | NL74897.068.20 |