Clinical trial NCT04658654: Cognitive Effects of Roflumilast in (a)MCI and Mild Dementia Patients
Official title: A Proof of Concept Phase II Study With the PDE4 Inhibitor Roflumilast in Patients With (Amnestic) Mild Cognitive Impairment (MCI) or Mild Dementia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Mild Cognitive Impairment
Mild Dementia
Amnestic Mild Cognitive Disorder
Keywords: MCI, amnestic MCI, mild dementia
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2020-12-08
Enrollment: 81
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the current project is to validate whether chronic intake (24 weeks) roflumilast (PDE4 inhibitor) can improve cognition in patients with (amnestic) mild cognitive impairment (MCI) and in patients with mild dementia. The project will demonstrate whether episodic memory, but also attention, information processing or executive function improves with chronic administration of roflumilast in (a)MCI and mild dementia patients.


Eligibility criteria: Inclusion Criteria:

* 50 to 90 years of age
* Willingness (including the informal caregiver) to sign an informed consent
* Body mass index (BMI) between 18.5 and 35
* MMSE of 20 or higher
* Clinical (amnestic)MCI or mild dementia diagnosis
* Memory performance on the delayed recall in the clinically relevant 15 words VLT of 1 or more SD below the average
* Clinical dementia rating (CDR) scale total score of 0.5 or 1
* Fazekas of 2 or lower

Exclusion Criteria:

* Normal Pressure Hydrocephalus (NPH)
* Fazekas of 3 or higher
* Morbus Huntington
* Parkinson's disease
* HIV/AIDS
* Hepatitis C \& B
* Recent Transient Ischemic Attack (TIA) (\< 2 years)
* Cerebrovascular Accident (CVA) (\< 2 years)
* TIA/CVA followed by cognitive decline (within 3 months)
* Chronic Obstructive Pulmonary Disease (COPD) gold criteria 3 or 4 and severe asthma
* History of schizophrenia, bipolar disorder or psychotic symptoms not otherwise specified or previous treatment for these diseases (lifetime)
* Current radiotherapy
* 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
* If patient does not have the possibility to be accompanied by the same informal caregiver during all test days

Primary outcomes:
measure: Verbal Learning Test (VLT) (15 words)
timeFrame: Change from baseline to 24 weeks of chronic intake
Secondary outcomes:
measure: Alzheimer's disease Assessment Scale- Cognitive Sub-scale (ADAS-Cog scale)
timeFrame: Change from baseline to 24 weeks of chronic intake
measure: Mini Mental State Examination (MMSE)
timeFrame: Change from baseline to 24 weeks of chronic intake
measure: Pattern Separation Task
timeFrame: Change from baseline to 24 weeks of chronic intake
measure: Trail-Making Test (TMT)
timeFrame: Change from baseline to 24 weeks of chronic intake
measure: Letter Digit Substitution Test (LDST)
timeFrame: Change from baseline to 24 weeks of chronic intake
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: Change from baseline to 24 weeks of chronic intake
measure: Alzheimer's disease co-operative study activities of daily living (ADCS-ADL) scale
timeFrame: Change from baseline to 24 weeks of chronic intake
measure: Neuropsychiatric Inventory (NPI)
timeFrame: Change from baseline to 24 weeks of chronic intake
measure: QoL-AD
timeFrame: Change from baseline to 24 weeks of chronic intake
measure: EuroQol
timeFrame: Change from baseline to 24 weeks of chronic intake
measure: Boston Naming Task
timeFrame: Change from baseline to 24 weeks of chronic intake
Other outcomes:
measure: Conversion to Alzheimer's disease (AD)
timeFrame: 24 weeks
measure: Pharmacokinetic validation of roflumilast and its active metabolite roflumilast N-Oxide in plasma
timeFrame: Acute, 12 weeks chronic intake and 24 weeks chronic intake
measure: Tau in tears
timeFrame: Change from baseline to 24 weeks of chronic intake
Locations:
city: Maastricht
country: Netherlands
facility: University of Maastricht, Faculty of Psychology and Neuropsychology
Study officials:
affiliation: Psychiatry and Neuropsychology, FHML, Maastricht University, the Netherlands.
name: Inez Ramakers, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Psychiatry and Neuropsychology, FHML, Maastricht University, the Netherlands
name: Frans Verhey, Prof. Dr.
role: STUDY_DIRECTOR
affiliation: Neuropsychology & Psychopharmacology, FPN, Maastricht University, The Netherlands
name: Arjan Blokland, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Psychiatry and Neuropsychology, FHML, Maastricht University, the Netherlands.
name: Jos Prickaerts, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: