Repurposing Bromocriptine for Abeta Metabolism in Alzheimer's Disease

NCT ID: NCT04413344

Last Updated: 2025-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-05
• Study Completion Date: 2021-11-24

Brief Summary

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.

Detailed 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.

Conditions

Familial Alzheimer Disease (FAD); PSEN1 Mutation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active

Bromocriptine mesilate, 2.5 to 22.5 mg per day, divided three times a day, for 50 weeks.

Group Type: ACTIVE_COMPARATOR

Bromocriptine Mesilate

Intervention Type: DRUG

Each tablet contains 2.87 mg of bromocriptine mesilate (JP) (2.5 mg of bromocriptine)

Placebo

Placebo, divided three times a day, for 50 weeks.

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

Identical tablets which contain no active ingredient

Interventions

Bromocriptine Mesilate

Each tablet contains 2.87 mg of bromocriptine mesilate (JP) (2.5 mg of bromocriptine)

Intervention Type: DRUG

Placebos

Identical tablets which contain no active ingredient

Intervention Type: DRUG

Other Intervention Names

TW-012R; Placebo

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 <= 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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mie University

OTHER

Sponsor Role: collaborator

Osaka University

OTHER

Sponsor Role: collaborator

Tokushima University

UNKNOWN

Sponsor Role: collaborator

Tokyo Metropolitan Institute for Geriatrics and Gerontology

UNKNOWN

Sponsor Role: collaborator

Asakayama Hospital

UNKNOWN

Sponsor Role: collaborator

Kawasaki Medical School Hospital

UNKNOWN

Sponsor Role: collaborator

Nagoya City University Hospital

UNKNOWN

Sponsor Role: collaborator

Time Therapeutics, Inc.

UNKNOWN

Sponsor Role: collaborator

Towa Pharmaceutical Co.,Ltd.

UNKNOWN

Sponsor Role: collaborator

Kyoto University

OTHER

Sponsor Role: lead

Responsible Party

Haruhisa Inoue

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Haruhisa Inoue, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Kyoto University

Hidekazu Tomimoto, MD, PhD

Role: STUDY_DIRECTOR

Mie University Hospital

Haruhiko Banno, MD, PhD

Role: STUDY_DIRECTOR

Kyoto University Hospital

Locations

Nagoya City University Hospital

Nagoya, Aichi-ken, Japan

Kyoto University Hospital

Kyoto, Kyoto, Japan

Mie University Hospital

Tsu, Mie-ken, Japan

Kawasaki Medical School Hospital

Kurashiki, Okayama-ken, Japan

Asakayama Hospital

Sakai, Osaka, Japan

Osaka University

Suita, Osaka, Japan

Tokushima University Hospital

Tokushima, Tokushima, Japan

Tokyo Metropolitan Institute for Geriatrics and Gerontology

Tokyo, Tokyo, Japan

Countries

Japan

References

Kondo T, Banno H, Okunomiya T, Amino Y, Endo K, Nakakura A, Uozumi R, Kinoshita A, Tada H, Morita S, Ishikawa H, Shindo A, Yasuda K, Taruno Y, Maki T, Suehiro T, Mori K, Ikeda M, Fujita K, Izumi Y, Kanemaru K, Ishii K, Shigenobu K, Kutoku Y, Sunada Y, Kawakatsu S, Shiota S, Watanabe T, Uchikawa O, Takahashi R, Tomimoto H, Inoue H. Repurposing bromocriptine for Abeta metabolism in Alzheimer's disease (REBRAnD) study: randomised placebo-controlled double-blind comparative trial and open-label extension trial to investigate the safety and efficacy of bromocriptine in Alzheimer's disease with presenilin 1 (PSEN1) mutations. BMJ Open. 2021 Jun 30;11(6):e051343. doi: 10.1136/bmjopen-2021-051343.

Reference Type: DERIVED

PMID: 34193504 (View on PubMed)

Other Identifiers

IACT19029

Identifier Type: -

Identifier Source: org_study_id