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

Medical University of Lodz

Status and phase: Enrolling; Phase 2

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

Treatments: Drug: dimethyl fumarate

Study type: Interventional

Funder types: Other

Identifiers

NCT06850597

010622

2022-002171-11 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 55 to 90 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Men and women aged 55-90 years.
2. 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.
3. MMSE score from 17 to 30 points.
4. CDR score from 0.5 to 2.
5. The patient signs an informed, voluntary consent to participate in the study.
6. The patient has a close person/de facto guardian who agrees to help the patient during participation in the study.
7. At least 6 years of education.
8. 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.

Exclusion criteria

1. Lack of informed voluntary consent to participate in the study.
2. Patients who cannot read or write.
3. Pregnant, breastfeeding or childbearing women who do not use effective contraception (hormonal contraception, surgical sterilization, intrauterine device, condom in combination with vaginal spermicide).
4. Participation in another clinical trial, currently or within 3 months prior to the screening visit.
5. Liver failure (i.e. cirrhosis or active liver disease), diagnosed acute or chronic hepatitis regardless of cause.
6. Chronic kidney disease with GFR below < 60 ml/min/m2
7. Abnormal liver parameters: ALAT exceeding > 2 times the upper limit of normal
8. Leukopenia (<4000/mm3), granulocytopenia (<1500/mm3) or lymphopenia (<1000/mm3) regardless of the cause.
9. Severe agitation.
10. Mental retardation.
11. Delirium diagnosed according to DSM-5 criteria.
12. Diagnosis of neurological and neurodegenerative diseases other than Alzheimer's disease (multiple sclerosis, Parkinson's disease, Huntington's disease, previous stroke).
13. 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.
14. 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).
15. Use of benzodiazepines or barbiturates within 1 week prior to screening.
16. Pharmacological immunosuppression.
17. Patients with bipolar disorder or psychotic disorders or any other psychiatric condition (current or past) that the Investigator believes interferes with the study.
18. Alcoholism or drug addiction as defined by DSM-5 within the past 5 years (dependent for more than 1 year and or in remission for less than 3 years).
19. Patients with any medical condition that, in the Investigator's judgment, is an exclusion criterion.
20. Thyroid hormone therapy initiated, discontinued, or modified within 3 months prior to screening visit.
21. Menopausal hormone replacement therapy initiated, discontinued, or modified within 3 months prior to screening visit.
22. Use of prohibited drugs in the study: Antineoplastic drugs (no studies). Immunosuppressive drugs (no studies). Corticosteroids (impact on project results). Live attenuated vaccines (no studies). Inactivated vaccines may be used. Benzodiazepines (impact on assessed endpoints). Other ethyl esters used orally or topically.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

30 participants in 10 patient groups, including a placebo group

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

Placebo Comparator group

Description:

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.

Treatment:

Drug: dimethyl fumarate

Assessment of the safety of therapy

Other group

Description:

Assessment of the safety of therapy

Treatment:

Drug: dimethyl fumarate

Assessment of the impact of therapy on patients' daily functioning

Placebo Comparator group

Description:

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

Treatment:

Drug: dimethyl fumarate

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

Placebo Comparator group

Description:

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

Treatment:

Drug: dimethyl fumarate

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

Placebo Comparator group

Description:

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 group

Description:

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)

Treatment:

Drug: dimethyl fumarate

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

Placebo Comparator group

Description:

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

Treatment:

Drug: dimethyl fumarate

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

Placebo Comparator group

Description:

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

Treatment:

Drug: dimethyl fumarate

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

Placebo Comparator group

Description:

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

Treatment:

Drug: dimethyl fumarate

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

Placebo Comparator group

Description:

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

Treatment:

Drug: dimethyl fumarate