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A Trial to Evaluate the Safety and Efficacy of Benfotiamine in Patients With Early Alzheimer's Disease (BenfoTeam)
NCT06223360 · Alzheimer's Disease Cooperative Study (ADCS)
In plain English
Click the button to translate this study into plain language — what it is, who qualifies, and what participation looks like.
Official title
A Seamless Phase 2A-Phase 2B Randomized Double-Blind Placebo- Controlled Trial to Evaluate the Safety and Efficacy of Benfotiamine in Patients With Early Alzheimer's Disease (BenfoTeam)
About this study
This is a randomized, double-blind, placebo-controlled 18-month clinical trial of benfotiamine in early AD. This trial will include a seamless phase 2A-2B design with a randomized total sample of 406 participants. Participants who are randomized but drop out prior to study drug exposure will be replaced.
Phase 2A of the trial will randomize approximately 150 participants total, in a 1:1:1 to treatment with 1200 mg/day benfotiamine, 600 mg/day benfotiamine or placebo. The primary objective of phase 2A is to determine the highest safe and well tolerated dose of benfotiamine (600 mg or 1200 mg), as evaluated by the rate of tolerability events (TEs), for advancement to long-term 72 week exposure. The highest tolerated dose of benfotiamine will be carried forward from phase 2A to phase 2B.
At the start of phase 2B, all participants enrolled in the two phase 2A active dose arms will receive a new supply of benfotiamine at the selected phase 2B dose. All phase 2A participants will be included in the phase 2 intent-to-treat efficacy population, as assigned to active or placebo treatment. The primary objective of phase 2B is to assess efficacy of benfotiamine on global function and cognition over 72 weeks. In phase 2B, a composite cognitive and functional measure as well as PD biomarkers will be used to evaluate efficacy during the extended treatment period. Phase 2B will also evaluate longer-term safety and tolerability of benfotiamine treatment over 72 weeks.
Eligibility criteria
Key Inclusion Criteria:
* Aged 50 to 89 (inclusive) at screening
* Mild Cognitive Impairment (MCI) due to AD or Mild dementia due to AD according to workgroups of the Diagnostic Guidelines of the National Institute on Aging and Alzheimer's Association (NIA-AA)
* Mini-Mental State Examination (MMSE) score 20-30 inclusive at screening-. Montreal Cognitive Assessment score (MoCA) \< 26 at screening
* Clinical Dementia Rating (CDR) global score of 0.5 or 1 with memory score of greater or equal to 0.5 at screening
* Positive plasma AD biomarker signature
* Participants who are treated with FDA-approved acetylcholinesterase inhibitors (AchEI)and/or memantine will have to be on a stable dosage regimen for at least 3 months prior to screening.
* Participants must have a study partner who has frequent interaction with them (approximately \>3-4 times per week), will be available for all clinic visits in person or remotely, and can assist in compliance with study procedures.
* Female participants must be post-menopausal for at least one year or surgically sterile(bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 6 months prior to screening.
* Fluent in English or Spanish to ensure compliance with cognitive testing and study visit procedures.
* Ambulatory, or able to walk with an assistive device.
* Provision of informed consent from the participant (or the participant's legally authorized representative (LAR) if unable to provide consent) and the study partner.
Key Exclusion Criteria:
* Significant neurological disorder other than AD (e.g. hypoxia, stroke, traumatic brain injury
* Significant neurodegenerative diseases, other than AD, and causes of dementias, Parkinson's disease and Huntington's disease, vascular dementia, CJD (Creutzfeldt-Jakob disease), LBD (Lewy Body dementia), PSP (Progressive Supranuclear Palsy), AIDS (Acquired Immunodeficiency Syndrome), or NPH (normal pressure hydrocephalus).
* Meeting Diagnostic Criteria for Possible AD according to workgroups of the Diagnostic Guidelines of the NIA-AA.
* A current diagnosis of uncontrolled Type I or Type II diabetes mellitus, as defined by Hemoglobin A1C (Hb A1C ≥ 8).
* A current active, uncontrolled seizure disorder.
* Diagnosis of cancer, except for those participants who have undergone potentially curative therapy with no evidence of recurrence for \> 5 years.
* History of alcoholism or substance abuse, current or within past 5 years.
* Previous exposure to Benfotiamine within past 3 months.
* Contraindication to MRI.
* Participation in another clinical trial for an investigational agent and having taken at least one dose of study drug, unless confirmed as having been on placebo, within 4 weeks prior to the baseline visit. The end of a previous investigational trial is defined as the date of the last dose of an investigational agent.
* Initiation of a monoclonal antibody treatment targeting brain amyloid within 6 months prior to the baseline visit.
* A disability that may prevent the patient from completing all study requirements e.g.,blindness, deafness, severe language difficulty).
Study design
Enrollment target: 406 participants
Allocation: randomized
Masking: triple
Age groups: adult, older_adult
Timeline
Starts: 2024-03-28
Estimated completion: 2027-12-01
Last updated: 2026-02-23
Interventions
Drug: Low Dose BenfotiamineDrug: High Dose BenfotiamineDrug: Placebo
Primary outcomes
- • Phase 2A: The rate of tolerability events (TEs). (Up to 72 weeks)
- • Phase 2B: The primary cognitive endpoint is the within-participant change from baseline to 72 weeks compared between active arms (benfotiamine) and placebo on the Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-Cog13). (72 weeks)
- • Phase 2B: The primary functional endpoint is the within-participant change from baseline to 72 weeks compared between active arm (benfotiamine) and placebo on the Clinical Dementia Rating - Sum of Boxes (CDR-SB). (72 weeks)
Sponsor
Alzheimer's Disease Cooperative Study (ADCS) · other
With: Burke Medical Research Institute, National Institute on Aging (NIA)
Contacts & investigators
ContactADCS Recruitment Team · contact · adcs-recruitment@health.ucsd.edu · 877-807-1290
ContactBryce Truver, MS · contact · btruver@health.ucsd.edu · 619-818-3769
InvestigatorHoward Feldman, MDCM · principal_investigator, Alzheimer's Disease Cooperative Study (ADCS)
InvestigatorGary E. Gibson, PhD · study_director, Burke Neurological Institute
InvestigatorJose A. Luchsinger, MD MPH · study_director, Columbia University
All locations (47)
St. Joseph's Hospital and Medical Center/Barrow Neurological InstituteRecruiting
Phoenix, Arizona, United States
Perseverance Research Center, LLCRecruiting
Scottsdale, Arizona, United States
Banner Sun Health Research InstituteRecruiting
Sun City, Arizona, United States
The Neuron ClinicRecruiting
Chula Vista, California, United States
University of California, IrvineRecruiting
Irvine, California, United States
Pacific Research NetworkTerminated
Lemon Grove, California, United States
University of Southern CaliforniaRecruiting
Los Angeles, California, United States
Cedars Sinai, Los AngelesRecruiting
Los Angeles, California, United States
Syrentis Clinical ResearchRecruiting
Santa Ana, California, United States
JEM Research InstituteRecruiting
Atlantis, Florida, United States
Brain Matters ResearchRecruiting
Delray Beach, Florida, United States
Neuropsychiatric Research Center of Southwest FloridaRecruiting
Fort Myers, Florida, United States
CCM Clinical Research Group, LLCRecruiting
Miami, Florida, United States
Gonzalez MD & Aswad MD Health ServicesRecruiting
Miami, Florida, United States
Miami Jewish HealthRecruiting
Miami, Florida, United States
Blue Medical Research Inc.Recruiting
Miami, Florida, United States
Brainstorm ResearchRecruiting
Miami, Florida, United States
Brain Matters Research (Kane Center)Recruiting
Stuart, Florida, United States
Conquest ResearchRecruiting
Winter Park, Florida, United States
Emory University Goizueta Alzheimer's Disease Research Center(GADRC)Recruiting
Atlanta, Georgia, United States
Sandhill Research, LLC d/b/a Accel Research SitesRecruiting
Decatur, Georgia, United States
Northwestern University Feinberg School of MedicineRecruiting
Chicago, Illinois, United States
Rush University Medical CenterRecruiting
Chicago, Illinois, United States
Southern Illinois UniversityRecruiting
Springfield, Illinois, United States
University of IowaRecruiting
Iowa City, Iowa, United States
University of KentuckyRecruiting
Lexington, Kentucky, United States
MedVadis ResearchRecruiting
Waltham, Massachusetts, United States
University of Michigan, Ann ArborRecruiting
Ann Arbor, Michigan, United States
Rutgers, Robert Wood Johnson Medical SchoolRecruiting
New Brunswick, New Jersey, United States
Albany Medical CollegeRecruiting
Albany, New York, United States
Dent Neurologic InstituteRecruiting
Amherst, New York, United States
Integrative Clinical TrialsRecruiting
Brooklyn, New York, United States
Weill Cornell Medical CollegeRecruiting
New York, New York, United States
Mount Sinai School of MedicineRecruiting
New York, New York, United States
Columbia University Irving Medical CenterRecruiting
New York, New York, United States
Nathan Kline Institute for Psychiatric ResearchRecruiting
New York, New York, United States
SUNY Upstate Medical UniversityRecruiting
Syracuse, New York, United States
AMC Research LLC, dba Flourish ResearchRecruiting
Matthews, North Carolina, United States
Case Western Reserve UniversityRecruiting
Cleveland, Ohio, United States
Ohio State UniversityRecruiting
Columbus, Ohio, United States
Oregon Health & Science University (OHSU)Recruiting
Portland, Oregon, United States
Geisinger Memory and Cognition CenterRecruiting
Wilkes-Barre, Pennsylvania, United States
Rhode Island HospitalRecruiting
Providence, Rhode Island, United States
Ralph H. Johnson VA Health Care SystemRecruiting
Charleston, South Carolina, United States
KCA NeurologyRecruiting
Tennessee City, Tennessee, United States
University of North Texas Health Science CenterRecruiting
Fort Worth, Texas, United States
Froedtert and Medical College of WisconsinRecruiting
Milwaukee, Wisconsin, United States