Efficacy and Safety of Dimethyl Fumarate Among Patients with Mild Cognitive Impairment and Dementia Due to Alzheimer's Disease

NCT06850597 | Recruiting Phase 2 DMC

• 2 other identifiers: 0106222022-002171-11
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to assess the degree of improvement in cognitive functions, including memory, attention, thinking, executive and language functions in diagnosed patients MCI and AD taking dimethyl fumarate 480 mg daily compared to patients taking placebo. Participant will be 55 to 90 years old, both genders. The main question it aims to answer is: Changing the degree of cognitive improvement based on the RBANS score among patients diagnosed with MCI and AD after completing dimethyl fumarate therapy test group compared to the placebo group.

Conditions

MCI; MCI-AD, Early Stage Alzheimer's Disease; Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Change in the degree of cognitive improvement based on the RBANS score among patients diagnosed with MCI and AD after completing dimethyl fumarate therapy test group compared to the placebo group.

  The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a neuropsychological measure used in the assessment of cognitive function in older adults, studies of mild cognitive impairment and Alzheimer's disease dementia, and studies evaluating the effectiveness of therapeutic interventions. The test generates index scores in five neurocognitive domains, as well as a Total Scale Index score. The RBANS is characterized by high sensitivity in detecting disease and assessing changes in scores during treatment in patients with MCI in the course of Alzheimer's disease. with MCI and AD after completing dimethyl fumarate therapy test group compared to the placebo group.

  15 months

Secondary Outcomes (6)

• Assessment of the safety of therapy

  15 months

• Assessment of the impact of therapy on the daily functioning of patients - Alzheimer's Disease Cooperative Study - Activity of Daily Living (ADCS-ADL) scale.

  15 months

• Assessment of the impact of therapy on the presence of neuropsychiatric symptoms/behavioral disorders in patients using the Neuropsychiatric Inventory (NPI) scale and the Geriatric Depression Scale (GDS).

  15 months

• Assessment of the impact of therapy on the quality of life of patients and their caregivers (EQ-5D scales; Zarit Burden Interview).

  12 months

• Assessment of the effect of therapy on the reduction of the degree of brain atrophy in patients from the active group compared to the control group (MRI study).

  6 months

Other Outcomes (3)

• Assessment of the effect of therapy on peripheral markers of oxidative stress and pro-inflammatory markers.

  6 months

• Assessment of the degree of reduction of the MCI progression rate to dementia after the end of the clinical phase of the study.

  12 months

• Assessment of the degree of improvement of cognitive functions using the MMSE and CDR scales.

  15 months

Study Arms (10)

Assessment of the degree of improvement in cognitive functions in diagnosed patients MCI and AD.

PLACEBO COMPARATOR

Assessment of the degree of improvement in cognitive functions, including memory, attention, thinking, executive and language functions in diagnosed patients MCI and AD taking dimethyl fumarate 480 mg daily compared to patients taking placebo.

Drug: dimethyl fumarate

Assessment of the safety of therapy

OTHER

Assessment of the safety of therapy

Drug: dimethyl fumarate

Assessment of the impact of therapy on patients' daily functioning

PLACEBO COMPARATOR

Assessment of the impact of therapy on patients' daily functioning - Scale Alzheimer's Disease Cooperative Study - Activity of Daily Living (ADCS-ADL).

Drug: dimethyl fumarate

Assessment of the impact of therapy on the presence of symptoms neuropsychiatric/behavioral disorder

PLACEBO COMPARATOR

Assessment of the impact of therapy on the presence of symptoms neuropsychiatric/behavioral disorders in patients scale Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS).

Drug: dimethyl fumarate

Assessment of the impact of therapy on the quality of life of patients and their caregivers

PLACEBO COMPARATOR

Assessment of the impact of therapy on the quality of life of patients and their caregivers (scales EQ-5D; Zarit Burden Interview).

reducing the degree of brain atrophy in patients - MRI examination

PLACEBO COMPARATOR

Assessment of the impact of therapy on reducing the degree of brain atrophy in patients from the active group compared to the control group (MRI examination)

Drug: dimethyl fumarate

impact of therapy on improvement in functional connections assessed in rs-fMRI rs-EEG

PLACEBO COMPARATOR

Assessment of the impact of therapy on improvement in functional connections assessed in rs-fMRI and rs-EEG

Drug: dimethyl fumarate

Effect of therapy on peripheral markers of oxidative stress and pro-inflammatory markers

PLACEBO COMPARATOR

Assessment of the effect of therapy on peripheral markers of oxidative stress and pro-inflammatory markers

Drug: dimethyl fumarate

degree of reduction in the rate of progression from MCI to dementia after completion

PLACEBO COMPARATOR

Assesment of the degree of reduction in the rate of progression from MCI to dementia after completion of the clinical phase of the study

Drug: dimethyl fumarate

degree of improvement in cognitive functions using the MMSE and CDR scales

PLACEBO COMPARATOR

Assessment of the degree of improvement in cognitive functions using the MMSE and CDR scales

Drug: dimethyl fumarate

Interventions

dimethyl fumarate DRUG

480 mg per day

Assessment of the degree of improvement in cognitive functions in diagnosed patients MCI and AD.; Assessment of the impact of therapy on patients' daily functioning; Assessment of the impact of therapy on the presence of symptoms neuropsychiatric/behavioral disorder; Assessment of the safety of therapy; Effect of therapy on peripheral markers of oxidative stress and pro-inflammatory markers; degree of improvement in cognitive functions using the MMSE and CDR scales; degree of reduction in the rate of progression from MCI to dementia after completion; impact of therapy on improvement in functional connections assessed in rs-fMRI rs-EEG; reducing the degree of brain atrophy in patients - MRI examination

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 55-90 years.
• Patients diagnosed with mild cognitive impairment in Alzheimer's disease and mild to moderate Alzheimer's dementia (MMSE \>16) diagnosed based on NIA-AA criteria.
• MMSE score from 17 to 30 points.
• CDR score from 0.5 to 2.
• The patient signs an informed, voluntary consent to participate in the study.
• The patient has a close person/de facto guardian who agrees to help the patient during participation in the study.
• At least 6 years of education.
• In the case of anti-Alzheimer's drugs, the use of cholinesterase inhibitors is permitted provided that they are included at least 3 months before entering the study and used at a stable dose for at least 60 days before entering the study. In the case of memantine, its use is permitted provided that it is included at least 4 months before entering the study and used at a stable dose for at least 3 months before entering the study.

You may not qualify if:

• Lack of informed voluntary consent to participate in the study.
• Patients who cannot read or write.
• Pregnant, breastfeeding or childbearing women who do not use effective contraception (hormonal contraception, surgical sterilization, intrauterine device, condom in combination with vaginal spermicide).
• Participation in another clinical trial, currently or within 3 months prior to the screening visit.
• Liver failure (i.e. cirrhosis or active liver disease), diagnosed acute or chronic hepatitis regardless of cause.
• Chronic kidney disease with GFR below \< 60 ml/min/m2
• Abnormal liver parameters: ALAT exceeding \> 2 times the upper limit of normal
• Leukopenia (\<4000/mm3), granulocytopenia (\<1500/mm3) or lymphopenia (\<1000/mm3) regardless of the cause.
• Severe agitation.
• Mental retardation.
• Delirium diagnosed according to DSM-5 criteria.
• Diagnosis of neurological and neurodegenerative diseases other than Alzheimer's disease (multiple sclerosis, Parkinson's disease, Huntington's disease, previous stroke).
• Presence of hemorrhagic foci in magnetic resonance imaging with a diameter of ≥ 2 cm3, more than three (3) ischemic stroke foci with a diameter of ≥ 1.5 cm3 or a single ischemic foci with a diameter of ≥ 2 cm3, presence of vascular malformations, aneurysms, subdural hematoma, normal pressure hydrocephalus, final decision at the discretion of the investigator.
• Severe or uncontrolled somatic disease that could affect the course of the study (e.g. neoplastic, cardiovascular, respiratory, metabolic or digestive, severe renal failure, unstable type I or II diabetes, untreated or uncontrolled clinically significant hypertension).
• Use of benzodiazepines or barbiturates within 1 week prior to screening.

Sponsors & Collaborators

• Medical University of Lodz: lead

Study Sites (1)

Department of Old Age Psychiatry and Psychotic Disorders Medical University of Lodz

Lodz, Łódź Voivodeship, 92-213, Poland

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Central Study Contacts

Medical University of Lodz Medical University of Lodz

CONTACT

+48 422725239; cwbk@umed.lodz.pl

Jakub Kazmierski, PhD

CONTACT

+48 426757372; jakub.kazmierski@umed.lodz.pl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Professor

Study Record Dates

• First Submitted: December 9, 2024
• First Posted: February 27, 2025
• Study Start: October 28, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 27, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)