Repurposing Bromocriptine for Abeta Metabolism in Alzheimer's Disease

NCT04413344 | Completed Phase 1 DMC

• 1 other identifier: IACT19029
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 8

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.

Conditions

Familial Alzheimer Disease (FAD); PSEN1 Mutation

Outcome Measures

Primary Outcomes (3)

• Safety (Incidence and severity of adverse events and adverse reactions)

  to assess safety

  Until Week 50 (end of trial)

• Severe impairment battery-Japanese version (SIB-J)

  to assess cognitive function

  Until Week 20 and 36

• Neuropsychiatric Inventory (NPI)

  to assess behavioral and psychiatric symptoms of dementia

  Until Week 20 and 36

Secondary Outcomes (11)

• Mental Function Impairment Scale (MENFIS)

  Until Week 20 and 36

• Mini-Mental State Examination-Japanese (MMSE-J)

  Until Week 20 and 36

• Disability Assessment for Dementia (DAD)

  Until Week 20 and 36

• Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III

  Until Week 20 and 36

• Apathy Scale

  Until Week 20 and 36

Other Outcomes (6)

• Wearable physical activity meter

  Until Week 20 and 36

• Finger tapping sensor readout

  Until Week 20 and 36

• Brain amyloid PET image

  Until Week 36

Study Arms (2)

Active

ACTIVE COMPARATOR

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

Drug: Bromocriptine Mesilate

Placebo

PLACEBO COMPARATOR

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

Drug: Placebos

Interventions

Bromocriptine Mesilate DRUG

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

Also known as: TW-012R

Active

Placebos DRUG

Identical tablets which contain no active ingredient

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kyoto University: lead
• Mie University: collaborator
• Osaka University: collaborator
• Tokushima University: collaborator
• Tokyo Metropolitan Institute for Geriatrics and Gerontology: collaborator
• Asakayama Hospital: collaborator
• Kawasaki Medical School Hospital: collaborator
• Nagoya City University Hospital: collaborator
• Time Therapeutics, Inc.: collaborator
• Towa Pharmaceutical Co.,Ltd.: collaborator

Study Sites (8)

Nagoya City University Hospital

Nagoya, Aichi-ken, 467-8602, Japan

Location

Kyoto University Hospital

Kyoto, Kyoto, 606-8507, Japan

Location

Mie University Hospital

Tsu, Mie-ken, 514-8507, Japan

Location

Kawasaki Medical School Hospital

Kurashiki, Okayama-ken, 701-0192, Japan

Location

Asakayama Hospital

Sakai, Osaka, 590-0018, Japan

Location

Osaka University

Suita, Osaka, 565-0871, Japan

Location

Tokushima University Hospital

Tokushima, Tokushima, 770-8503, Japan

Location

Tokyo Metropolitan Institute for Geriatrics and Gerontology

Tokyo, Tokyo, 173-0015, Japan

Location

Related Publications (1)

• 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.

  PMID: 34193504 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Bromocriptine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Ergotamines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Ergolines; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Study Officials

• Haruhisa Inoue, MD, PhD

  Kyoto University

  PRINCIPAL INVESTIGATOR

• Hidekazu Tomimoto, MD, PhD

  Mie University Hospital

  STUDY DIRECTOR

• Haruhiko Banno, MD, PhD

  Kyoto University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: \[Double-blind phase\] Multicenter, randomized, placebo-controlled, double-blind, parallel-group comparison clinical trial \[Extension phase\] Multicenter, open-label, extension trial

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 2, 2020
• Study Start: June 5, 2020
• Primary Completion: November 24, 2021
• Study Completion: November 24, 2021
• Last Updated: August 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After publication
• Access Criteria: Reasonable request

Locations

JP (8)