Roflumilast to Treat Cognitive Sequela After Stroke

NCT04854811 | Completed Phase 2 DMC

• 1 other identifier: NL74897.068.20
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cerebrovascular Disorders; Memory; Functional Recovery; Drug Intervention

Keywords

Cerebrovascular Disorders; Plasticity; Phosphodiesterase inhibitor; Memory; Roflumilast

Outcome Measures

Primary Outcomes (1)

• 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

  Change from baseline to 12 weeks of chronic intake

Secondary Outcomes (7)

• Verbal Learning Test (VLT)

  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

  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)

  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)

  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

  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)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo oral capsule, once daily for 12 weeks

Drug: Roflumilast Oral Tablet

Roflumilast (100 microgram)

EXPERIMENTAL

once daily for 12 weeks

Drug: Roflumilast Oral Tablet

Interventions

Roflumilast Oral Tablet DRUG

Once daily for 12 weeks

Also known as: EU: Daxas, US: Daliresp, PDE4 inhibitor

Placebo; Roflumilast (100 microgram)

Eligibility Criteria

• Age: 41 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• Normal Pressure Hydrocephalus (NPH)
• Morbus Huntington
• Parkinson's disease
• HIV/AIDS
• Hepatitis C \& B
• Recent Transient Ischemic Attack (TIA) (\< 1 years)
• 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

Sponsors & Collaborators

• Maastricht University: lead
• Netherlands Brain Foundation: collaborator

Study Sites (1)

Maastricht University

Maastricht, Limburg, 6200 MD, Netherlands

Location

MeSH Terms

Conditions

Cerebrovascular Disorders

Interventions

Roflumilast; Phosphodiesterase 4 Inhibitors

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Ieke Winkens, Dr.

  Assistant Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Pharmacy will distribute pills with a code
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Between subjects, double blind, placebo-controlled, randomized

Study Record Dates

• First Submitted: March 31, 2021
• First Posted: April 22, 2021
• Study Start: July 7, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: January 17, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)