Repurposing Bromocriptine for Abeta Metabolism in Alzheimer's Disease (REBRAnD)

Kyoto University

Status and phase

Completed

Phase 2

Phase 1

Conditions

PSEN1 Mutation

Familial Alzheimer Disease (FAD)

Treatments

Drug: Placebos

Drug: Bromocriptine Mesilate

Study type

Interventional

Funder types

Other

Identifiers

NCT04413344

IACT19029

Details and patient eligibility

About

The goal of this clinical trial is to learn about safety and efficacy of bromocriptine in familial Alzheimer's disease with presenilin 1 mutations.

The main questions it aims to answer are: •safety of bromocriptine •efficacy of bromocriptine

Participants will answer questions, have blood exams, lumbar punctures and MRI/PET scans. Researchers will compare a participants group taking bromocriptine with a participants group taking placebo to see if there is any changes in cognitive function, and behavioral and psychiatric symptoms with dementia.

Full description

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.

Enrollment

8 patients

Sex

All

Ages

20+ years old

Volunteers

No Healthy Volunteers

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 <= 17 or >= 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