Mild Cognitive Impairment (MCI)
Conditions
Interventions
Trade Name: Daxas (EU)
Pharmaceutical Form: Capsule, soft
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use
Sponsors
ZonMw
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 50 to 90 years of age; - willingness (both the participant and informal caregiver) to sign an IC; - body mass index (BMI) between 18.5 and 30; - MMSE of 20 or higher; - MCI due to AD diagnosis which includes either increased cerebrospinal fluid (CSF) amyloid-beta marker and/or a positive biomarker of neuronal injury i.e. magnetic resonance imaging (MRI) scan including measurements of decreased hippocampal volume or medial temporal atrophy by volumetric measures or visual rating); - memory performance on the delayed recall in the 15 words VLT of 1-2 standard deviation(s) (SD) below the average. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 81 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 81
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participating in this study: receiving current irradiation, HIV positive, Hepatitis B/C, Normal Pressure Hydrocephalus (NPH), Morbus Huntington, Parkinson's disease, recent Transient Ischemic Attack (TIA) or Cerebrovascular Accident (CVA) (< 2 years), TIA/CVA followed by cognitive decline (within 3 months), COPD, 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) centrally acting beta-blockers, 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 and other similar 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. Lastly, if a participant does not have the possibility to be accompanied at every test session by the same informal caregiver they will be excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the proposed proof-of-concept phase II study is to validate the effect of roflumilast on episodic memory, namely the verbal learning test (VLT) immediate and delayed recall (15 words), in MCI patients after chronic roflumilast treatment of 24 weeks. ;Secondary Objective: Our secondary objective is multifaceted. Other cognitive domains will be measured using: -the Letter Digit Substitution test ; -the Trail-making test (TMT); -the Pattern Separation Task; -the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) (minus the word recall task and the word recognition task), -VLT recognition; -and the Mini-Mental State Examination (MMSE). Additionally, wellbeing and quality of life questionnaires regarding the participant, namely EuroQol, quality of life AD (QoLAD) and Hospital Anxiety and Depression Scale (HADS), and his/her informal caregiver, namely the Neuropsychiatric Inventory (NPI) and the Alzheimer’s Disease Cooperative Study Activities of Daily Living Scale (ADCS ADL-MCI), are included to gain more insight in the relation between (improved) cognition, quality of life, mood and emotion. We do take tau measurement from tears in to our measurements, as well as the conversion from MCI to AD (yes/no). ;Primary end point(s): Expected increase in verbal learning task (VLT) recall in words in the immediate and in the delayed condition (15 words) at 24 weeks. ;Timepoint(s) of evaluation of this end point: Baseline Acute at 12 weeks of chronic intake of Roflumilast at 24 weeks of chronic intake of Roflumilast 2 weeks follow up post 24 weeks of chronic intake of Roflumilast | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Expected increased recognition score on the VLT. In addition, a decrease in the reaction time (RT) in the Trail-making test, LDST, as well as a decrease in the amount of errors in the LDST is expected. We expect an improvement in scores in the MMSE and the ADAS-Cog, as well as an increase in score regarding the wellbeing, mood and quality of life questionnaires for both the patient and the informal caregiver.;Timepoint(s) of evaluation of this end point: Acute (except MMSE) at 12 weeks of chronic intake of Roflumilast at 24 weeks of chronic intake of Roflumilast 2 weeks follow up post 24 weeks of chronic intake of Roflumilast | — |
Countries
Netherlands
Contacts
Public ContactPrinicipal Investigator
Maastricht University
Outcome results
None listed