A nationwide Phase 2A-2B clinical trial, named Benfoteam, is now enrolling participants to investigate benfotiamine as a novel treatment for early Alzheimer's disease. The trial, spurred by decades of research led by neuroscientist Dr. Gary Gibson, aims to evaluate whether benfotiamine, a synthetic form of vitamin B1, can slow the progression of Alzheimer's by targeting thiamine deficiency and improving glucose metabolism in brain cells.
The Benfoteam study seeks to enroll 406 patients aged 50 to 89 with mild cognitive impairment or mild dementia due to Alzheimer's across 50 sites. Participants will be monitored over 18 months to determine the highest safe and well-tolerated dose of benfotiamine and whether it improves global function and cognition. The trial began enrolling patients in April 2024.
Thiamine Deficiency and Alzheimer's: A New Target
Dr. Gibson's research posits that thiamine deficiency alters glucose metabolism in brain cells, leading to the formation of amyloid plaques and tau tangles, which are hallmarks of Alzheimer's. "Our approach is just the opposite: We think thiamine deficiency alters glucose metabolism in brain cells, and that's what leads to the formation of plaques and tangles," said Dr. Gibson. "Therefore, treating brain thiamine deficiency may be a better treatment target."
Preclinical and Pilot Study Evidence
Preclinical studies demonstrated that benfotiamine addressed key clinical and biological characteristics of Alzheimer's, including impaired cognition, amyloid plaques, abnormal tau protein accumulation, lower glucose metabolism, oxidative stress, and inflammation. A pilot clinical trial in 2015, involving 70 patients with mild cognitive impairment or early Alzheimer's, showed encouraging results. The increase in the Alzheimer's Disease Assessment Scale-Cognitive Subscale was 43% lower in the benfotiamine group than in the placebo group, suggesting reduced cognitive decline. The pilot study also indicated potential for improving cognitive and functional outcomes.
Trial Design and Biomarker Analysis
The Benfoteam trial will utilize advanced blood biomarker technologies in collaboration with international research groups. These include assessing thiamine levels with the University of Cambridge, evaluating abnormal glucose use with the University of Virginia, assessing tau tangles, neuron loss, and inflammation with the University of Gothenburg, Sweden, and evaluating amyloid plaques with C2N Diagnostics. The primary objectives of the trial are to determine the highest safe and well-tolerated dose of benfotiamine and whether it can improve global function and cognition over 18 months.
Benfotiamine vs. Existing Treatments
Dr. Gibson highlighted the potential advantages of benfotiamine over recently approved Alzheimer's drugs like lecanemab and donanemab, which are administered intravenously and target amyloid plaques. "As an oral medication, benfotiamine is much more convenient, less expensive and, we believe, may do a much better job of targeting the root cause of the disease," he stated.
Dr. Gibson cautioned against using over-the-counter vitamin B1 supplements as a substitute for participating in the trial, emphasizing that the study drug is manufactured to specific standards and unregulated benfotiamine products may not be safe or effective.
