A Trial to Evaluate the Safety and Efficacy of Benfotiamine in Patients With Early Alzheimer's Disease (BenfoTeam)

February 20, 2026 updated by: Alzheimer's Disease Cooperative Study (ADCS)

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)

The purpose of this study is to learn more about the safety, effectiveness and tolerability of the study drug called Benfotiamine which may delay or slow the progression of the symptoms of early Alzheimer's disease.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

406

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Recruiting
        • St. Joseph's Hospital and Medical Center/Barrow Neurological Institute
      • Scottsdale, Arizona, United States, 85253
        • Recruiting
        • Perseverance Research Center, LLC
      • Sun City, Arizona, United States, 85351
        • Recruiting
        • Banner Sun Health Research Institute
    • California
      • Chula Vista, California, United States, 91910
        • Recruiting
        • The Neuron Clinic
      • Irvine, California, United States, 92697
        • Recruiting
        • University of California, Irvine
      • Lemon Grove, California, United States, 91945
        • Terminated
        • Pacific Research Network
      • Los Angeles, California, United States, 90033
        • Recruiting
        • University of Southern California
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars Sinai, Los Angeles
      • Santa Ana, California, United States, 92705
        • Recruiting
        • Syrentis Clinical Research
    • Florida
      • Atlantis, Florida, United States, 33462
        • Recruiting
        • Jem Research Institute
      • Delray Beach, Florida, United States, 33445
        • Recruiting
        • Brain Matters Research
      • Fort Myers, Florida, United States, 33912
        • Recruiting
        • Neuropsychiatric Research Center of Southwest Florida
      • Miami, Florida, United States, 33133
        • Recruiting
        • CCM Clinical Research Group, LLC
      • Miami, Florida, United States, 33176
        • Recruiting
        • Brainstorm Research
      • Miami, Florida, United States, 33137
        • Recruiting
        • Miami Jewish Health
      • Miami, Florida, United States, 33135
        • Recruiting
        • Gonzalez MD & Aswad MD Health Services
      • Miami, Florida, United States, 33144
        • Recruiting
        • Blue Medical Research Inc.
      • Stuart, Florida, United States, 34997
        • Recruiting
        • Brain Matters Research (Kane Center)
      • Winter Park, Florida, United States, 32789
        • Recruiting
        • Conquest Research
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Recruiting
        • Emory University Goizueta Alzheimer's Disease Research Center(GADRC)
      • Decatur, Georgia, United States, 30030
        • Recruiting
        • Sandhill Research, LLC d/b/a Accel Research Sites
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University Feinberg School of Medicine
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Southern Illinois University
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa
    • Kentucky
      • Lexington, Kentucky, United States, 40504
        • Recruiting
        • University of Kentucky
    • Massachusetts
      • Waltham, Massachusetts, United States, 02451
        • Recruiting
        • MedVadis Research
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan, Ann Arbor
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Rutgers, Robert Wood Johnson Medical School
    • New York
      • Albany, New York, United States, 12208
        • Recruiting
        • Albany Medical College
      • Amherst, New York, United States, 14226
        • Recruiting
        • Dent Neurologic Institute
      • Brooklyn, New York, United States, 11229
        • Recruiting
        • Integrative Clinical Trials
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Irving Medical Center
      • New York, New York, United States, 10021
        • Recruiting
        • Weill Cornell Medical College
      • New York, New York, United States, 10029
        • Recruiting
        • Mount Sinai School of Medicine
      • New York, New York, United States, 10962
        • Recruiting
        • Nathan Kline Institute for Psychiatric Research
      • Syracuse, New York, United States, 13210
        • Recruiting
        • SUNY Upstate Medical University
    • North Carolina
      • Matthews, North Carolina, United States, 28105
        • Recruiting
        • AMC Research LLC, dba Flourish Research
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • Case Western Reserve University
      • Columbus, Ohio, United States, 43221
        • Recruiting
        • Ohio State University
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health & Science University (OHSU)
    • Pennsylvania
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Recruiting
        • Geisinger Memory and Cognition Center
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Rhode Island Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29401
        • Recruiting
        • Ralph H. Johnson VA Health Care System
    • Tennessee
      • Tennessee City, Tennessee, United States, 37067
        • Recruiting
        • KCA Neurology
    • Texas
      • Fort Worth, Texas, United States, 76107
        • Recruiting
        • University of North Texas Health Science Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Froedtert and Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low Dose Benfotiamine
Participants will take 300mg benfotiamine capsules twice a day (BID; once in the morning and once in the evening).
Drug: Low Dose Benfotiamine
300mg benfotiamine capsules (BID, twice a day)
Experimental: High Dose Benfotiamine
Participants will take 600mg benfotiamine capsules twice a day (BID; once in the morning and once in the evening).
Drug: High Dose Benfotiamine
600mg benfotiamine capsules (BID, twice a day)
Placebo Comparator: Placebo
Participants will take placebo capsules twice a day (BID; once in the morning and once in the evening). In the placebo group, capsules will be filled with inactive microcrystalline cellulose. The other capsule components, shape and color are identical between benfotiamine and placebo arms.
Drug: Placebo
Placebo capsules to mimic benfotiamine capsules (BID, twice a day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Time Frame: 72 weeks
ADAS-Cog13 is a structured psychometric scale that evaluates memory (immediate and delayed word recall; immediate word recognition), receptive and expressive language, orientation, ideational praxis (preparing a letter for mailing), constructional praxis (copying figures), and attention (number cancellation). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions also are obtained. ADAS-Cog13 total score has a range of 0-85; with higher scores indicating greater impairment.
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).
Time Frame: 72 weeks
CDR-SB is a composite rating of cognition and everyday function which incorporates both informant input and direct assessment of performance. It assesses through semi-structured interview three cognitive domains (memory, orientation, and judgement/problem solving) and three everyday functional domains (community affairs, home and hobbies, personal care). Level of impairment in each of the six domains is rated from none (score=0) to severe (score=3). The six domain scores are then summed to create the CDR-SB. Range 0-18; higher scores indicate greater impairment.
72 weeks
Phase 2A: The rate of tolerability events (TEs).
Time Frame: Up to 72 weeks
The primary safety outcome in phase 2A is the rate of tolerability events (TEs) compared between active arms (benfotiamine) and placebo arms, at each dose. A TE is counted when either a participant discontinues study drug due to intolerability or experiences a moderate or severe adverse event (AE) that is determined to be possibly, probably or definitely related to study drug.
Up to 72 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 2B: within-participant change from baseline to 72 weeks compared between active (benfotiamine) arms and placebo arm on The Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale for use in Mild Cognitive Impairment (ADCS-ADL-MCI).
Time Frame: 72 weeks
The ADCS-ADL-MCI is a structured questionnaire completed with the informant to assess the participant's ability to perform basic and instrumental activities of daily living. Activities assessed include dressing; social and occupational functioning; household chores and use of tools; interest in and ability to carry out hobbies; shopping and meal preparation; managing appointments; using a phone and computer/tablet.
72 weeks
Phase 2B: within-participant change from baseline to 72 weeks compared between active arms (benfotiamine) and placebo arm on the Montreal Cognitive Assessment (MoCA).
Time Frame: 72 weeks
The MoCA is a brief mental status exam, which assesses numerous cognitive domains, including attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Range: 0-30; lower scores indicate more cognitive impairment.
72 weeks
Number of Participants With Adverse Events (AEs) and Serious AEs.
Time Frame: 72 weeks
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in participants or clinical investigation participants administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is defined as any event that met any of the following criteria at any dose: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received study drug; other important medical events that may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the other serious outcomes. An AE is considered "Related" for causality designations of possible, probable and definite. The number of AEs and SAEs will be compared between active arms (benfotiamine) and placebo arm.
72 weeks
Number of Participant Withdrawals from the study.
Time Frame: 72 weeks
Number of participant withdrawals from the study for all reasons during the study period (baseline to 72 weeks). Number of participant withdrawals will be compared between active arms (benfotiamine) and placebo arm.
72 weeks
Number of Participant Drug Discontinuations.
Time Frame: 72 weeks
Number of participant drug discontinuations during the study period (baseline to 72 weeks). Number of participant drug discontinuations will be compared between active arms (benfotiamine) and placebo arm.
72 weeks
Mean and Median Thiamine levels (nmol/L).
Time Frame: Baseline, week 72
Measures of thiamine will be provided as blood markers of efficacy of drug delivery. These measurements will be conducted on whole blood and red blood cells. Blood samples to measure mean and median thiamine levels (nmol/L) will be collected on all participants and results compared between active arms (benfotiamine) and placebo arm at baseline and week 72.
Baseline, week 72
Mean and Median Thiamine Diphosphate (ThDP) levels (nmol/L).
Time Frame: Baseline, week 72
Measures of thiamine diphosphate (ThDP) will be provided as blood markers of efficacy of drug delivery. These measurements will be conducted on whole blood and red blood cells. Blood samples to measure mean and median Thiamine Diphosphate (ThDP) levels (nmol/L) will be collected on all participants and results compared between active arms (benfotiamine) and placebo arm at baseline and week 72.
Baseline, week 72
Mean and Median Thiamine Monophosphate (ThMP) levels (nmol/L).
Time Frame: Baseline, week 72
Measures of thiamine monophosphate (ThMP) will be provided as blood markers of efficacy of drug delivery. These measurements will be conducted on whole blood and red blood cells. Blood samples to measure mean and median Thiamine Monophosphate (ThMP) levels (nmol/L) will be collected on all participants and results compared between active arms (benfotiamine) and placebo arm at baseline and week 72.
Baseline, week 72
Mean and Median levels of ThDP Activation of Transketolase (U/g haemoglobin (U/gHb)).
Time Frame: Baseline, week 72
Measures of ThDP activation of transketolase will be provided as blood markers of efficacy of drug delivery. These measurements will be conducted on whole blood and red blood cells. Blood samples to measure mean and median hDP Activation of Transketolase (U/g haemoglobin (U/gHb)) will be collected on all participants and results compared between active arms (benfotiamine) and placebo arm at baseline and week 72.
Baseline, week 72

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alzheimer's Disease Cooperative Study (ADCS)

Collaborators

National Institute on Aging (NIA)
Burke Medical Research Institute

Investigators

  • Principal Investigator: Howard Feldman, MDCM, Alzheimer's Disease Cooperative Study (ADCS)
  • Study Director: Gary E. Gibson, PhD, Burke Neurological Institute
  • Study Director: Jose A. Luchsinger, MD MPH, Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 28, 2024

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

December 20, 2023

First Submitted That Met QC Criteria

January 16, 2024

First Posted (Actual)

January 25, 2024

Study Record Updates

Last Update Posted (Actual)

February 23, 2026

Last Update Submitted That Met QC Criteria

February 20, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ADC-061-BENFO
  • 1R01AG076634-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data sharing is integral to the ADCS's mission to develop and execute innovative clinical trials focused on interventions that may prevent, delay, or treat the expression of Alzheimer's disease and related dementias. The ADCS is committed to sharing resources and tools, including data, biospecimens, trial designs, outcome and analysis measures following NIH guidelines.

IPD Sharing Time Frame

6 months after publication.

IPD Sharing Access Criteria

Data requestors must complete an ADCS data and sample sharing request form. Upon approval, requestors must complete a data use agreement prior to accessing the data.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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