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REBRAnD: Repurposing Bromocriptine for Abeta Metabolism in Alzheimer's Disease

Sponsor
Kyoto University (Other)
Overall Status
Completed
CT.gov ID
NCT04413344
Collaborator
Mie University (Other), Osaka University (Other), Tokushima University (Other), Tokyo Metropolitan Geriatric Medical Center (Other), Asakayama Hospital (Other), Kawasaki Medical School Hospital (Other), Nagoya City University Hospital (Other), Time Therapeutics, Inc. (Other), Towa Pharmaceutical Co.,Ltd. (Other)
8
Enrollment
8
Locations
2
Arms
17.3
Actual Duration (Months)
1
Patient Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
8 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
[Double-blind phase] Multicenter, randomized, placebo-controlled, double-blind, parallel-group comparison clinical trial [Extension phase] Multicenter, open-label, extension trial[Double-blind phase] Multicenter, randomized, placebo-controlled, double-blind, parallel-group comparison clinical trial [Extension phase] Multicenter, open-label, extension trial
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 5, 2020
Actual Primary Completion Date :
Nov 15, 2021
Actual Study Completion Date :
Nov 15, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Active

Drug: Bromocriptine
TW-012R: Each tablet contains 2.87 mg of bromocriptine mesilate (JP) (2.5 mg of bromocriptine)
Placebo Comparator: Placebo

Drug: Placebos
Placebo: Identical tablets which contain no active ingredient

Outcome Measures

Primary Outcome Measures

  1. Safety (Incidence and severity of adverse events and adverse reactions) [Until Week 50 (end of trial)]

  2. Severe impairment battery-Japanese version (SIB-J) [Until Week 20 and 36]

  3. Neuropsychiatric Inventory (NPI) [Until Week 20 and 36]

Secondary Outcome Measures

  1. Mental Function Impairment Scale (MENFIS) [Until Week 20 and 36]

  2. Mini-Mental State Examination-Japanese (MMSE-J) [Until Week 20 and 36]

  3. Disability Assessment for Dementia (DAD) [Until Week 20 and 36]

  4. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III [Until Week 20 and 36]

  5. Apathy Scale [Until Week 20 and 36]

  6. Plasma Aβ protein concentration [Until Week 20 and 36]

  7. Plasma NfL protein concentration [Until Week 20 and 36]

  8. Plasma Total Tau, Plasma p-Tau concentration [Until Week 20 and 36]

  9. Cerebrospinal fluid (CSF) Aβ concentration [Until Week 36]

  10. CSF Total Tau, CSF p-Tau concentration [Until Week 36]

  11. Blood bromocriptine concentration [Until Week 20 and 36]

Other Outcome Measures

  1. Wearable physical activity meter [Until Week 20 and 36]

  2. Finger tapping sensor readout [Until Week 20 and 36]

  3. Brain amyloid PET image [Until Week 36]

  4. Brain tau PET image [Until Week 36]

  5. Upper motor neuron burden score [Until Week 20 and 36]

  6. Plasma Aβ-related peptides concentration [Until Week 20 and 36]

Eligibility Criteria

Criteria

Ages Eligible for Study:
20 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Nagoya City University Hospital Nagoya Aichi Japan 467-8602
2 Mie University Hospital Tsu Mie Japan 514-8507
3 Kawasaki Medical School Hospital Kurashiki Okayama Japan 701-0192
4 Asakayama Hospital Sakai Osaka Japan 590-0018
5 Osaka University Suita Osaka Japan 565-0871
6 Kyoto University Hospital Kyoto Japan 606-8507
7 Tokushima University Hospital Tokushima Japan 770-8503
8 Tokyo Metropolitan Geriatric Hospital Tokyo Japan 173-0015

Sponsors and Collaborators

  • Kyoto University
  • Mie University
  • Osaka University
  • Tokushima University
  • Tokyo Metropolitan Geriatric Medical Center
  • Asakayama Hospital
  • Kawasaki Medical School Hospital
  • Nagoya City University Hospital
  • Time Therapeutics, Inc.
  • Towa Pharmaceutical Co.,Ltd.

Investigators

  • Principal Investigator: Haruhisa Inoue, MD, PhD, Kyoto University
  • Study Director: Hidekazu Tomimoto, MD, PhD, Mie University Hospital
  • Study Director: Haruhiko Banno, MD, PhD, Kyoto University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Haruhisa Inoue, Professor, Kyoto University
ClinicalTrials.gov Identifier:
NCT04413344
Other Study ID Numbers:
  • IACT19029
First Posted:
Jun 2, 2020
Last Update Posted:
Apr 7, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Alzheimer Disease
Bromocriptine

Study Results

No Results Posted as of Apr 7, 2022