Alzheimers disease patients with PSEN1 mutations Dementia, Alzheimers disease, familial, genetic, presenilin 1
Conditions
Interventions
[Double -blind phase]
1) Low-dose maintenance period (start of trial treatment--Week20)
Oral administration of the trial drug (TW-012R or placebo) will be started at 1 tablet once a day immediately af
Sponsors
Tomimoto Hidekazu
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Alzheimer's disease patients with PSEN1 mutations 2. Patients diagnosed with "probable AD" according to the diagnostic guideline of NIA-AA or "probable Alzheimer-type dementia" according to the diagnostic criteria for Alzheimer's disease specified in DSM-5 3. An MMSE-J score of =20 years at the time of giving informed consent 8. Written informed consent has been obtained from the patient or his/her legally acceptable representative to participate in this trial
Exclusion criteria
Exclusion criteria: 1. Difficulty with the oral intake of tablets 2. Patients receiving anti-dementia drugs who have changed the dosing regimen during the 2 months prior to giving informed consent 3. Patients with dementia due to pathology other than Alzheimer's disease (e.g., vascular dementia, frontotemporal dementia, Lewy body dementia, progressive supranuclear palsy, corticobasal degeneration, Huntington's disease, and prion disease) 4. Presence of clinically relevant or unstable mental disorders. Patients with major depression in remission can be enrolled. 5. Imminent risk of self-harm or harm to others 6. Body mass index (BMI) of = 35 7. Patients with a history of alcohol dependence, drug dependence, or drug abuse within the 5 years before providing informed consent 8. HBs antigen positive 9. Anti-HIV antibody positive 10. Anti-HTLV-1 antibody positive 11. Patients with an active infection, such as hepatitis C and syphilis (STS/TPHA) 12. Patients with the following liver function values on the test before enrollment - AST(GOT) > 4.0 x Upper limit of the institutional reference range or - ALT (GPT) > 4.0 x Upper limit of the institutional reference range 13. Patients who have uncontrolled, clinically significant medical conditions (e.g., diabetes melitus, hypertension, thyroid/endocrine disease, congestive cardiac failure, angina pectoris, cardiac/gastrointestinal disease, dialysis, and abnormal renal function with an estimated CLcr =470 msec, female: >= 480 msec), or patients with a history/complication of torsades de pointes 15. Patients with a history of malignancies within 5 years prior to providing informed consent. However, patients with the following diseases can be enrolled if they are treated appropriately: - Skin cancer (basal cell, squamous cell) - Cervical carcinoma in situ - Localized prostate cancer - Malignancies that have not recurred for at least 3 years since surgery and the patient's physician has determined that the risk of recurrence is low 16. Patients with clinically significant vitamin B1/B12 deficiency or folic acid deficiency within 6 months prior to giving informed consent 17. Patients who have participated in other clinical research/trials involving interventions within the 3 months prior to providing informed consent 18. Patients who have previously received bromocriptine or TW-012R 19. Patients with a history of hypersensitivity to bromocriptine or ergot alkaloids 20. Patients with current or a history of thickened heart valve cusps, restricted heart valve motion, and the associated heart valve lesions, such as stenosis, confirmed by echocardiography 21. Pregnant females, lactating females, females who may be pregnant (pregnancy test will be done to see if she is pregnant), or females who wish to become pregnant 22. Other patients who are considered inappropriate to participate in this trial at the discretion of the investigator or sub-investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1)Safety (incidence and severity of adverse events and adverse reactions) 2)Efficacy: SIB-J 3)Efficacy: NPI | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy 1) MENFIS 2) MMSE-J 3) DAD 4) UPDRS part III 5) Apathy Scale 6) Plasma Abeta protein 7) Plasma NfL protein 8) Plasma Total Tau, Plasma p-Tau 9) CSF Abeta 10) CSF Total Tau, CSF p-Tau 11) Blood bromocriptine concentration 1) Wearable physical activity meter 2) Finger tapping 3) Brain amyloid PET 4) Brain tau PET 5) Upper motor neuron burden 6) Plasma Abeta related peptides | — |
Contacts
Public ContactHaruhiko Banno
Kyoto University Hospital
Outcome results
None listed