NCT04658654

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
81

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Nov 2021

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 31, 2020

Completed
3 months until next milestone

First Posted

Study publicly available on registry

December 8, 2020

Completed
12 months until next milestone

Study Start

First participant enrolled

November 19, 2021

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2023

Completed
Last Updated

April 21, 2022

Status Verified

April 1, 2022

Enrollment Period

1.9 years

First QC Date

August 31, 2020

Last Update Submit

April 13, 2022

Conditions

Keywords

MCI, amnestic MCI, mild dementia

Outcome Measures

Primary Outcomes (1)

  • Verbal Learning Test (VLT) (15 words)

    Change from baseline to 24 weeks of chronic intake

Secondary Outcomes (11)

  • 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

  • +6 more secondary outcomes

Other Outcomes (3)

  • Conversion to Alzheimer's disease (AD)

    24 weeks

  • Pharmacokinetic validation of roflumilast and its active metabolite roflumilast N-Oxide in plasma

    Acute, 12 weeks chronic intake and 24 weeks chronic intake

  • Tau in tears

    Change from baseline to 24 weeks of chronic intake

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo oral capsule, once daily for 24 weeks

Drug: Placebo oral tablet

Roflumilast 50ug

EXPERIMENTAL

Roflumilast (50 microgram) oral capsule, once daily for 24 weeks

Drug: Roflumilast

Roflumilast 100ug

EXPERIMENTAL

Roflumilast (100 microgram) oral capsule, once daily for 24 weeks

Drug: Roflumilast

Interventions

chronic intervention (24 weeks): roflumilast capsule

Also known as: EU: Daxas, US: Daliresp, PDE4 inhibitor
Roflumilast 100ugRoflumilast 50ug

Pill with inactive ingredients to mimic same appearance of roflumilast capsule

Also known as: Placebo
Placebo

Eligibility Criteria

Age50 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Maastricht, Faculty of Psychology and Neuropsychology

Maastricht, Netherlands

RECRUITING

Related Publications (1)

  • Possemis N, Verhey F, Prickaerts J, Blokland A, Ramakers I. A proof of concept phase II study with the PDE-4 inhibitor roflumilast in patients with mild cognitive impairment or mild Alzheimer's disease dementia (ROMEMA): study protocol of a double-blind, randomized, placebo-controlled, between-subjects trial. Trials. 2024 Mar 4;25(1):162. doi: 10.1186/s13063-024-08001-3.

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

RoflumilastPhosphodiesterase 4 Inhibitors

Condition Hierarchy (Ancestors)

Cognition DisordersNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Phosphodiesterase InhibitorsEnzyme InhibitorsMolecular Mechanisms of Pharmacological ActionPharmacologic ActionsChemical Actions and Uses

Study Officials

  • Inez Ramakers, Dr.

    Psychiatry and Neuropsychology, FHML, Maastricht University, the Netherlands.

    PRINCIPAL INVESTIGATOR
  • Frans Verhey, Prof. Dr.

    Psychiatry and Neuropsychology, FHML, Maastricht University, the Netherlands

    STUDY DIRECTOR
  • Arjan Blokland, Prof. Dr.

    Neuropsychology & Psychopharmacology, FPN, Maastricht University, The Netherlands

    PRINCIPAL INVESTIGATOR
  • Jos Prickaerts, Prof. Dr.

    Psychiatry and Neuropsychology, FHML, Maastricht University, the Netherlands.

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 31, 2020

First Posted

December 8, 2020

Study Start

November 19, 2021

Primary Completion

October 1, 2023

Study Completion

October 1, 2023

Last Updated

April 21, 2022

Record last verified: 2022-04

Data Sharing

IPD Sharing
Will not share

Locations