Cognitive Effects of Roflumilast in (a)MCI and Mild Dementia Patients

Study Overview
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Brief Summary
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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.

Official Title
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A Proof of Concept Phase II Study With the PDE4 Inhibitor Roflumilast in Patients With (Amnestic) Mild Cognitive Impairment (MCI) or Mild Dementia

Conditions
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Mild Cognitive Impairment, Mild Dementia, Amnestic Mild Cognitive Disorder

Intervention / Treatment
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* Drug: Roflumilast
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo oral capsule, once daily for 24 weeks | Drug: Placebo oral tablet<br>* Pill with inactive ingredients to mimic same appearance of roflumilast capsule<br>* Other names: Placebo;|
| Experimental: Roflumilast 50ug<br>Roflumilast (50 microgram) oral capsule, once daily for 24 weeks | Drug: Roflumilast<br>* chronic intervention (24 weeks): roflumilast capsule<br>* Other names: PDE4 inhibitor;|
| Experimental: Roflumilast 100ug<br>Roflumilast (100 microgram) oral capsule, once daily for 24 weeks | Drug: Roflumilast<br>* chronic intervention (24 weeks): roflumilast capsule<br>* Other names: PDE4 inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Verbal Learning Test (VLT) (15 words) |  | Change from baseline to 24 weeks of chronic intake | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's disease Assessment Scale- Cognitive Sub-scale (ADAS-Cog scale) |  | Change from baseline to 24 weeks of chronic intake | 
| Mini Mental State Examination (MMSE) |  | Change from baseline to 24 weeks of chronic intake | 
| Pattern Separation Task |  | Change from baseline to 24 weeks of chronic intake | 
| Trail-Making Test (TMT) |  | Change from baseline to 24 weeks of chronic intake | 
| Letter Digit Substitution Test (LDST) |  | Change from baseline to 24 weeks of chronic intake | 
| Hospital Anxiety and Depression Scale (HADS) |  | Change from baseline to 24 weeks of chronic intake | 
| Alzheimer's disease co-operative study activities of daily living (ADCS-ADL) scale |  | Change from baseline to 24 weeks of chronic intake | 
| Neuropsychiatric Inventory (NPI) |  | Change from baseline to 24 weeks of chronic intake | 
| QoL-AD |  | Change from baseline to 24 weeks of chronic intake | 
| EuroQol |  | Change from baseline to 24 weeks of chronic intake | 
| Boston Naming Task |  | Change from baseline to 24 weeks of chronic intake | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MCI, amnestic MCI, mild dementia