Familial Alzheimer Disease (FAD)Phase 1/2REBRAnDNCT04413344
Repurposing Bromocriptine for Abeta Metabolism in Alzheimer's Disease
A Phase 1/2 study testing Bromocriptine Mesilate in people with Familial Alzheimer Disease (FAD) and PSEN1 Mutation, run by Kyoto University at 8 sites in Japan.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Familial Alzheimer Disease (FAD), PSEN1 Mutation
- What is being tested?
- Bromocriptine Mesilate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 8 sitesJapan
- Study dates
- 5 Jun 2020to 24 Nov 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 28Show fewer
- 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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Japan8 sites
Kawasaki Medical School Hospital
Kurashiki, Okayama-ken, 701-0192
Kyoto University Hospital
Kyoto, Kyoto, 606-8507
Nagoya City University Hospital
Nagoya, Aichi-ken, 467-8602
Asakayama Hospital
Sakai, Osaka, 590-0018
Osaka University
Suita, Osaka, 565-0871
Tokushima University Hospital
Tokushima, Tokushima, 770-8503
Tokyo Metropolitan Institute for Geriatrics and Gerontology
Tokyo, Tokyo, 173-0015
Mie University Hospital
Tsu, Mie-ken, 514-8507
About this study
Official title: Double-Blind Comparative Trial and Open-Label Extension Trial to Investigate the Safety and Efficacy of TW-012R in Alzheimer's Disease With Presenilin 1 (PSEN1) Mutations
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.
Read the 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
- Being tested
- Bromocriptine Mesilate, Placebos
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bromocriptine MesilateDrug
Also called TW-012R
Each tablet contains 2.87 mg of bromocriptine mesilate (JP) (2.5 mg of bromocriptine)
PlacebosDrug
Also called Placebo
Identical tablets which contain no active ingredient
| Study group | Role | What they receive |
|---|---|---|
| Active | Active comparator | Bromocriptine mesilate, 2.5 to 22.5 mg per day, divided three times a day, for 50 weeks. Receives: Drug: Bromocriptine Mesilate |
| Placebo | Placebo comparator | Placebo, divided three times a day, for 50 weeks. Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (Incidence and severity of adverse events and adverse reactions)
to assess safety
Measured: Until Week 50 (end of trial)
Severe impairment battery-Japanese version (SIB-J)
to assess cognitive function
Measured: Until Week 20 and 36
Neuropsychiatric Inventory (NPI)
to assess behavioral and psychiatric symptoms of dementia
Measured: Until Week 20 and 36
Secondary outcomes (11)
Mental Function Impairment Scale (MENFIS)
to assess cognitive function
Measured: Until Week 20 and 36
Mini-Mental State Examination-Japanese (MMSE-J)
to assess cognitive function
Measured: Until Week 20 and 36
Disability Assessment for Dementia (DAD)
to assess activities of daily living
Measured: Until Week 20 and 36
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III
to assess motor symptoms and signs
Measured: Until Week 20 and 36
Apathy Scale
to assess apathy
Measured: Until Week 20 and 36
Plasma Aβ protein concentration
to assess Aβ protein metabolism
Measured: Until Week 20 and 36
Plasma NfL protein concentration
to assess neurodegeneration
Measured: Until Week 20 and 36
Plasma Total Tau, Plasma p-Tau concentration
to assess tau protein metabolism
Measured: Until Week 20 and 36
Cerebrospinal fluid (CSF) Aβ concentration
to assess Aβ protein metabolism
Measured: Until Week 36
CSF Total Tau, CSF p-Tau concentration
to assess tau protein metabolism
Measured: Until Week 36
Blood bromocriptine concentration
to assess safety
Measured: Until Week 20 and 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2020
- Study start5 Jun 2020
- Primary completion24 Nov 2021
- Study completion24 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Familial Alzheimer Disease (FAD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- \[Double-blind phase\] Multicenter, randomized, placebo-controlled, double-blind, parallel-group comparison clinical trial \[Extension phase\] Multicenter, open-label, extension trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kyoto University
- Sponsor type
- University, hospital or other
- Collaborators
- Mie University, Osaka University, Tokushima University, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Asakayama Hospital, Kawasaki Medical School Hospital, Nagoya City University Hospital, Time Therapeutics, Inc., Towa Pharmaceutical Co.,Ltd.
- Responsible party
- Principal investigator, Haruhisa Inoue, Kyoto University
- Investigators
- Haruhisa Inoue, MD, PhD, Principal investigator, Kyoto UniversityHidekazu Tomimoto, MD, PhD, Study director, Mie University HospitalHaruhiko Banno, MD, PhD, Study director, Kyoto University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04413344
- Sponsor's protocol ID
- IACT19029
- Acronym
- REBRAnD
- Status last verified
- Aug 2025
- First submitted
- 28 May 2020
- Last updated
- 29 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual data from all the participants are illustrated in the figures and in appendix of journal article. Any data shown will be available from the corresponding author on reasonable request.
Publications
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.
PubMed 34193504
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-Blind Comparative Trial and Open-Label Extension Trial to Investigate the Safety and Efficacy of TW-012R in Alzheimer's Disease With Presenilin 1 (PSEN1) Mutations
- ClinicalTrials.gov ID
- NCT04413344
- Acronym / sponsor ID
- REBRAnD / IACT19029
- Conditions
- Familial Alzheimer Disease (FAD), PSEN1 Mutation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Kyoto UniversityUniversity, hospital or other
- Collaborators
- Mie University, Osaka University, Tokushima University, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Asakayama Hospital, Kawasaki Medical School Hospital, Nagoya City University Hospital, Time Therapeutics, Inc., Towa Pharmaceutical Co.,Ltd.
- Study start
- 5 Jun 2020 (actual)
- Primary completion
- 24 Nov 2021 (actual)
- Study completion
- 24 Nov 2021 (actual)
- First posted
- 2 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- [Double-blind phase] Multicenter, randomized, placebo-controlled, double-blind, parallel-group comparison clinical trial [Extension phase] Multicenter, open-label, extension trial
| Arm | Type | Receives |
|---|---|---|
| Active | Active comparator | Drug: Bromocriptine MesilateBromocriptine mesilate, 2.5 to 22.5 mg per day, divided three times a day, for 50 weeks. |
| Placebo | Placebo comparator | Drug: PlacebosPlacebo, divided three times a day, for 50 weeks. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bromocriptine MesilateAlso: TW-012REach tablet contains 2.87 mg of bromocriptine mesilate (JP) (2.5 mg of bromocriptine) | Drug | Active |
| PlacebosAlso: PlaceboIdentical tablets which contain no active ingredient | Drug | Placebo |
Primary outcome
Safety (Incidence and severity of adverse events and adverse reactions)
Time frame: Until Week 50 (end of trial)
to assess safety
Severe impairment battery-Japanese version (SIB-J)
Time frame: Until Week 20 and 36
to assess cognitive function
Neuropsychiatric Inventory (NPI)
Time frame: Until Week 20 and 36
to assess behavioral and psychiatric symptoms of dementia
11 secondary outcomes
Mental Function Impairment Scale (MENFIS)
Time frame: Until Week 20 and 36
Mini-Mental State Examination-Japanese (MMSE-J)
Time frame: Until Week 20 and 36
Disability Assessment for Dementia (DAD)
Time frame: Until Week 20 and 36
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III
Time frame: Until Week 20 and 36
Apathy Scale
Time frame: Until Week 20 and 36
Plasma Aβ protein concentration
Time frame: Until Week 20 and 36
Plasma NfL protein concentration
Time frame: Until Week 20 and 36
Plasma Total Tau, Plasma p-Tau concentration
Time frame: Until Week 20 and 36
Cerebrospinal fluid (CSF) Aβ concentration
Time frame: Until Week 36
CSF Total Tau, CSF p-Tau concentration
Time frame: Until Week 36
Blood bromocriptine concentration
Time frame: Until Week 20 and 36
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2025.
- Derived from this study: PubMed 34193504Kondo 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.
- Individual participant dataSharing planned: Yes. Individual data from all the participants are illustrated in the figures and in appendix of journal article. Any data shown will be available from the corresponding author on reasonable request.
Related trials for Familial Alzheimer Disease (FAD)
RecruitingObservational study
China HEalthy Aging and Dementia Study (HEAD)
Alzheimer Disease (AD), Mild Cognitive Impairment (MCI)
RecruitingPhase 2/3
A Study of Donanemab, RG6289, or the Combination of Donanemab and RG6289 in Presenilin 1 (PSEN1) E280A Mutation Carriers for the Treatment of Autosomal-Dominant Alzheimer's Disease
Autosomal Dominant Alzheimers Disease, Early Onset Alzheimer Disease
RecruitingObservational study
The Chinese Familial Alzheimer's Network
Alzheimer Disease, Familial Alzheimer Disease (FAD)
RecruitingObservational study
China Cognition and Aging Study
Mild Cognitive Impairment(MCI), Alzheimer Disease, Late Onset
RecruitingPhase 1
A Trial Evaluating the Effect of NIO752 on Tau Synthesis Measured by a Process Known as SILK
Alzheimer Disease, Autosomal Dominant Alzheimer Disease Due to Mutation of Presenilin 1 (Disorder)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Haruhisa Inoue, MD, PhD principal investigator
Kyoto University
Hidekazu Tomimoto, MD, PhD study director
Mie University Hospital
Haruhiko Banno, MD, PhD study director
Kyoto University Hospital
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bromocriptine Mesilate in people with Familial Alzheimer Disease (FAD) and PSEN1 Mutation, run by Kyoto University at 8 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (Incidence and severity of adverse events and adverse reactions) (time frame: Until Week 50 (end of trial)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04413344, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2025.