repurposing bromocriptine for abeta metabolism in alzheimer's disease

Conditions: Familial Alzheimer Disease (FAD); PSEN1 Mutation

Summary: to investigate the safety and efficacy of an orally administered dose of tw-012r in patients with alzheimer's disease bearing psen1 (presenilin 1) mutations (psen1-ad), using a placebo group as a control. in addition, long-term safety will be examined in an open-label extension trial.


Eligibility criteria:
inclusion criteria: * alzheimer's disease patients with psen1 mutations * 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 * an mmse-j score of \<= 25 * patients whose cognitive function and everyday function are obviously impaired based on their medical record or information provided by a person who knows the patient well * patients for whom intellectual disability and mental disorders other than dementia can be ruled out based on their academic background, work history, and life history. * patients with a reliable and close relationship with a partner/caregiver * age\>=20 years at the time of giving informed consent * written informed consent has been obtained from the patient or his/her legally acceptable representative to participate in this trial exclusion criteria: * difficulty with the oral intake of tablets * patients receiving anti-dementia drugs who have changed the dosing regimen during the 2 months prior to giving informed consent * 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) * presence of clinically relevant or unstable mental disorders. patients with major depression in remission can be enrolled. * imminent risk of self-harm or harm to others * body mass index (bmi) of \ = 35 * patients with a history of alcohol dependence, drug dependence, or drug abuse within the 5 years before providing informed consent * hbs antigen positive * anti-hiv antibody positive * anti-htlv-1 antibody positive * patients with an active infection, such as hepatitis c and syphilis (sts/tpha) * 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 * 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 \< 30 ml/min)within 3 months prior to giving informed consent in addition to the underlying disease to be investigated in the trial and for whom the investigator or sub-investigator considers that there is a significant medical risk in the patient's participation in the trial * patients with long qt syndrome or tendency toward prolonged qtc interval (male: \>=470 msec, female: \>= 480 msec), or patients with a history/complication of torsades de pointes * 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 * patients with clinically significant vitamin b1/b12 deficiency or folic acid deficiency within 6 months prior to giving informed consent * patients who have participated in other clinical research/trials involving interventions within the 3 months prior to providing informed consent * patients who have previously received bromocriptine or tw-012r * patients with a history of hypersensitivity to bromocriptine or ergot alkaloids * 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 * pregnant females, lactating females, females who may be pregnant, and females who wish to become pregnant * other patients who are considered inappropriate to participate in this trial at the discretion of the investigator or sub-investigator