Cerebrovascular DisordersPhase 2ROSTMEMANCT04854811
Roflumilast to Treat Cognitive Sequela After Stroke
A Phase 2 study testing Roflumilast Oral Tablet in people with Cerebrovascular Disorders and Memory, run by Maastricht University at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 41 to 70 years
- Conditions the study is for
- Cerebrovascular Disorders, Memory, Functional Recovery
- What is being tested?
- Roflumilast Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteNetherlands
- Study dates
- 7 Jul 2021to 1 Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 41 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willingness to sign an informed consent
- Body mass index (BMI) between 18.5 and 35
- Suffered a stroke at least one year ago; and at the age of 40 or later
- Objective cognitive complaint: memory performance on the delayed recall in the 15 words VWLT of below the normative score (corrected for education, sex and age)
Who cannot join
- Normal Pressure Hydrocephalus (NPH)
- Morbus Huntington
- Parkinson's disease
- HIV/AIDS
- Hepatitis C \& B
- Recent Transient Ischemic Attack (TIA) (< 1 years)
Show all 17Show fewer
- Cerebrovascular Accident (<1 years)
- Chronic Obstructive Pulmonary Disease (COPD) type Gold 3 and 4
- History of schizophrenia, bipolar disorder or psychotic symptoms not otherwise specified or previous treatment for these diseases (lifetime)
- Risk of suicidal behaviour
- 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.
- Current treatment with (or illicit use of) cannabis, opiates, benzodiazepines, MDMA and cocaine
- 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 or CYP1A2
- Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
- Patients participating in other drug studies
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Proof of Concept Phase II Study With the PDE4 Inhibitor Roflumilast in People Suffering From Long-term Cognitive Sequela After Stroke
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.
Read the 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)."
- Being tested
- Roflumilast Oral Tablet
- Keywords
- Cerebrovascular Disorders, Plasticity, Phosphodiesterase inhibitor, Memory, Roflumilast
- Medical subject headings
- Cerebrovascular Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Roflumilast Oral TabletDrug
Also called EU: Daxas, US: Daliresp, PDE4 inhibitor
Once daily for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo oral capsule, once daily for 12 weeks Receives: Drug: Roflumilast Oral Tablet |
| Roflumilast (100 microgram) | Experimental | once daily for 12 weeks Receives: Drug: Roflumilast Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Verbal Learning Test (VLT) Verbal Learning Test (VLT) (15 words) (delayed recall) [ Time Frame: Change from baseline to 12 weeks of chronic intake ] Verbal Learning Test (VLT)
15 words, delayed recall
Measured: Change from baseline to 12 weeks of chronic intake
Secondary outcomes (7)
Verbal Learning Test (VLT)
15 words, delayed recall
Measured: Change from baseline to effects one hour after the first intake (acute effects), to 6 weeks of chronic intake and to 12 weeks after the end of treatment (long-term effects)
Rivermead Behavioural Memory Test
Measured: Change from baseline to effects one hour after the first intake (acute effects), to 6 weeks of chronic intake, to 12 weeks of chronic intake and to 12 weeks after the end of treatment (long-term effects)
Digit Symbol Substitution Test (DSST)
Measured: Change from baseline to effects one hour after the first intake (acute effects), to 6 weeks of chronic intake, to 12 weeks of chronic intake and to 12 weeks after the end of treatment (long-term effects)
Trail Making Test (TMT)
Measured: Change from baseline to effects one hour after the first intake (acute effects), to 6 weeks of chronic intake, to 12 weeks of chronic intake and to 12 weeks after the end of treatment (long-term effects)
Everyday Memory Questionnaire
Measured: Change from baseline to effects one hour after the first intake (acute effects), to 6 weeks of chronic intake, to 12 weeks of chronic intake and to 12 weeks after the end of treatment (long-term effects)
the total mood score of the Hospital Anxiety and Depression Scale questionnaire (HADS)
Measured: Change from baseline to effects one hour after the first intake (acute effects), to 6 weeks of chronic intake, to 12 weeks of chronic intake and to 12 weeks after the end of treatment (long-term effects)
Mood and well-being: Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-Participation) (USER-P)
Measured: Change from baseline to effects one hour after the first intake (acute effects), to 6 weeks of chronic intake, to 12 weeks of chronic intake and to 12 weeks after the end of treatment (long-term effects)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2021
- Study start7 Jul 2021
- Primary completion1 Dec 2023
- Study completion1 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebrovascular DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Between subjects, double blind, placebo-controlled, randomized
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University
- Sponsor type
- University, hospital or other
- Collaborators
- Netherlands Brain Foundation
- Responsible party
- Sponsor
- Investigators
- Ieke Winkens, Dr., Principal investigator, Assistant Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04854811
- Sponsor's protocol ID
- NL74897.068.20
- Acronym
- ROSTMEMA
- Status last verified
- Jan 2024
- First submitted
- 31 Mar 2021
- Last updated
- 17 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof of Concept Phase II Study With the PDE4 Inhibitor Roflumilast in People Suffering From Long-term Cognitive Sequela After Stroke
- ClinicalTrials.gov ID
- NCT04854811
- Acronym / sponsor ID
- ROSTMEMA / NL74897.068.20
- Keywords
- Cerebrovascular Disorders, Plasticity, Phosphodiesterase inhibitor, Memory, Roflumilast
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Maastricht UniversityUniversity, hospital or other
- Collaborators
- Netherlands Brain Foundation
- Study start
- 7 Jul 2021 (actual)
- Primary completion
- 1 Dec 2023 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 22 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)."
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Between subjects, double blind, placebo-controlled, randomized
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Roflumilast Oral TabletPlacebo oral capsule, once daily for 12 weeks |
| Roflumilast (100 microgram) | Experimental | Drug: Roflumilast Oral Tabletonce daily for 12 weeks |
Who may qualify
- Ages
- 41 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Willingness to sign an informed consent
- Body mass index (BMI) between 18.5 and 35
- Suffered a stroke at least one year ago; and at the age of 40 or later
- Objective cognitive complaint: memory performance on the delayed recall in the 15 words VWLT of below the normative score (corrected for education, sex and age)
Key exclusion criteria (17 listed)
- Normal Pressure Hydrocephalus (NPH)
- Morbus Huntington
- Parkinson's disease
- HIV/AIDS
- Hepatitis C \& B
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Roflumilast Oral TabletAlso: EU: Daxas, US: Daliresp, PDE4 inhibitorOnce daily for 12 weeks | Drug | Placebo, Roflumilast (100 microgram) |
Primary outcome
Verbal Learning Test (VLT) Verbal Learning Test (VLT) (15 words) (delayed recall) [ Time Frame: Change from baseline to 12 weeks of chronic intake ] Verbal Learning Test (VLT)
Time frame: Change from baseline to 12 weeks of chronic intake
15 words, delayed recall
7 secondary outcomes
Verbal Learning Test (VLT)
Time frame: Change from baseline to effects one hour after the first intake (acute effects), to 6 weeks of chronic intake and to 12 weeks after the end of treatment (long-term effects)
Rivermead Behavioural Memory Test
Time frame: Change from baseline to effects one hour after the first intake (acute effects), to 6 weeks of chronic intake, to 12 weeks of chronic intake and to 12 weeks after the end of treatment (long-term effects)
Digit Symbol Substitution Test (DSST)
Time frame: Change from baseline to effects one hour after the first intake (acute effects), to 6 weeks of chronic intake, to 12 weeks of chronic intake and to 12 weeks after the end of treatment (long-term effects)
Trail Making Test (TMT)
Time frame: Change from baseline to effects one hour after the first intake (acute effects), to 6 weeks of chronic intake, to 12 weeks of chronic intake and to 12 weeks after the end of treatment (long-term effects)
Everyday Memory Questionnaire
Time frame: Change from baseline to effects one hour after the first intake (acute effects), to 6 weeks of chronic intake, to 12 weeks of chronic intake and to 12 weeks after the end of treatment (long-term effects)
the total mood score of the Hospital Anxiety and Depression Scale questionnaire (HADS)
Time frame: Change from baseline to effects one hour after the first intake (acute effects), to 6 weeks of chronic intake, to 12 weeks of chronic intake and to 12 weeks after the end of treatment (long-term effects)
Mood and well-being: Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-Participation) (USER-P)
Time frame: Change from baseline to effects one hour after the first intake (acute effects), to 6 weeks of chronic intake, to 12 weeks of chronic intake and to 12 weeks after the end of treatment (long-term effects)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ieke Winkens, Dr. principal investigator
Assistant Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Roflumilast Oral Tablet in people with Cerebrovascular Disorders and Memory, run by Maastricht University at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Verbal Learning Test (VLT) Verbal Learning Test (VLT) (15 words) (delayed recall) [ Time Frame: Change from baseline to 12 weeks of chronic intake ] Verbal Learning Test (VLT) (time frame: Change from baseline to 12 weeks of chronic intake). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2024.