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

Mild Cognitive Impairment Clinical Trial

— ROMEMA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04658654
• Other study ID #: 72476
• Status: Recruiting
• Phase: Phase 2
• Start date: November 19, 2021
• Est. completion date: October 2023

Study information

• Verified date: April 2022
• Source: Maastricht University Medical Center
• Contact: Nina Possemis, MSc.
• Phone: +31 (0)43 388 1022
• Email: n.possemis[@]maastrichtuniversity.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 81
• Est. completion date: October 2023
• Est. primary completion date: October 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Cognition Disorders
• Cognitive Dysfunction
• Dementia
• Mild Cognitive Impairment
• Mild Dementia

Intervention

Drug:
• Roflumilast
chronic intervention (24 weeks): roflumilast capsule
• Placebo oral tablet
Pill with inactive ingredients to mimic same appearance of roflumilast capsule

Locations

Country	Name	City	State
Netherlands	University of Maastricht, Faculty of Psychology and Neuropsychology	Maastricht

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Conversion to Alzheimer's disease (AD)		24 weeks
Other	Pharmacokinetic validation of roflumilast and its active metabolite roflumilast N-Oxide in plasma		Acute, 12 weeks chronic intake and 24 weeks chronic intake
Other	Tau in tears		Change from baseline to 24 weeks of chronic intake
Primary	Verbal Learning Test (VLT) (15 words)		Change from baseline to 24 weeks of chronic intake
Secondary	Alzheimer's disease Assessment Scale- Cognitive Sub-scale (ADAS-Cog scale)		Change from baseline to 24 weeks of chronic intake
Secondary	Mini Mental State Examination (MMSE)		Change from baseline to 24 weeks of chronic intake
Secondary	Pattern Separation Task		Change from baseline to 24 weeks of chronic intake
Secondary	Trail-Making Test (TMT)		Change from baseline to 24 weeks of chronic intake
Secondary	Letter Digit Substitution Test (LDST)		Change from baseline to 24 weeks of chronic intake
Secondary	Hospital Anxiety and Depression Scale (HADS)		Change from baseline to 24 weeks of chronic intake
Secondary	Alzheimer's disease co-operative study activities of daily living (ADCS-ADL) scale		Change from baseline to 24 weeks of chronic intake
Secondary	Neuropsychiatric Inventory (NPI)		Change from baseline to 24 weeks of chronic intake
Secondary	QoL-AD		Change from baseline to 24 weeks of chronic intake
Secondary	EuroQol		Change from baseline to 24 weeks of chronic intake
Secondary	Boston Naming Task		Change from baseline to 24 weeks of chronic intake