Benfotiamine for Alzheimer's Disease

Recruiting at 45 trial locations

Overseen By Bryce Truver, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alzheimer's Disease Cooperative Study (ADCS)

Must be taking: Acetylcholinesterase inhibitors, Memantine

Disqualifiers: Neurological disorders, Diabetes, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

406 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Benfotiamine to determine if it can safely slow the symptoms of early Alzheimer's disease. Participants will receive either a high dose, low dose, or a placebo (a pill with no active drug) to compare effects. The trial targets individuals diagnosed with mild cognitive impairment or mild dementia due to Alzheimer's who are already on stable medication. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that if you are taking FDA-approved medications for Alzheimer's, like acetylcholinesterase inhibitors or memantine, you must be on a stable dose for at least 3 months before joining. The protocol does not specify about other medications, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that benfotiamine is safe for use. In a previous study involving individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD), oral benfotiamine proved safe and well-tolerated, with participants reporting no major side effects.

Another study found that benfotiamine not only slowed memory and thinking problems but also reduced levels of harmful substances called AGEs, suggesting it might help protect brain health.

Overall, these findings indicate that benfotiamine is safe and well-tolerated, making it a promising option for those considering participation in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard Alzheimer's treatments that often focus on managing symptoms using medications like cholinesterase inhibitors and NMDA receptor antagonists, benfotiamine offers a novel approach by potentially targeting the underlying metabolic pathways involved in the disease. Benfotiamine, a derivative of vitamin B1, is thought to enhance glucose metabolism and reduce harmful substances in the brain, which may help in slowing the progression of Alzheimer's. Researchers are excited about this treatment because it taps into these metabolic processes, potentially offering a new way to combat the disease beyond traditional symptom management.

What evidence suggests that Benfotiamine might be an effective treatment for Alzheimer's?

Research has shown that benfotiamine might help with Alzheimer's disease. In an earlier study, people with mild memory problems and early Alzheimer's who took benfotiamine demonstrated better brain function. Specifically, their memory and thinking skills declined 43% less than those who did not take benfotiamine. The treatment proved safe and easy for participants to handle. These results suggest that benfotiamine could help slow down Alzheimer's symptoms. In this trial, participants will receive either a high dose or a low dose of benfotiamine, or a placebo, to further evaluate its effectiveness and safety. ^{1 3 5 6 7}

Who Is on the Research Team?

Howard Feldman, MDCM

Principal Investigator

Alzheimer's Disease Cooperative Study (ADCS)

Gary E. Gibson, PhD

Principal Investigator

Burke Neurological Institute

Jose A. Luchsinger, MD MPH

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for individuals aged 50-89 with early Alzheimer's, confirmed by specific biomarkers. They must be able to walk (with assistance if needed), have a certain level of cognitive function, and speak English or Spanish. Women should be post-menopausal or surgically sterile. Participants need a committed study partner and may take stable Alzheimer's medications.

Inclusion Criteria

I am between 50 and 89 years old.

Mini-Mental State Examination (MMSE) score 20-30 inclusive at screening

Fluent in English or Spanish to ensure compliance with cognitive testing and study visit procedures

Exclusion Criteria

My diabetes is not well-controlled, with an HbA1C level of 8 or higher.

Contraindication to MRI

Meeting Diagnostic Criteria for Possible AD according to workgroups of the Diagnostic Guidelines of the NIA-AA

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 2A Treatment

Participants are randomized to receive either 1200 mg/day benfotiamine, 600 mg/day benfotiamine, or placebo to determine the highest safe and well-tolerated dose

Up to 72 weeks

Phase 2B Treatment

Participants receive the selected phase 2B dose of benfotiamine to assess efficacy on global function and cognition

72 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Benfotiamine

Trial Overview

The BenfoTeam trial is testing the safety and effectiveness of Benfotiamine in slowing down early Alzheimer's symptoms. It involves comparing a placebo with low and high doses of Benfotiamine to see which works better at delaying symptom progression.

How Is the Trial Designed?

Group I: Low Dose Benfotiamine Experimental Treatment 1 Intervention

Participants will take 300mg benfotiamine capsules twice a day (BID; once in the morning and once in the evening).

Group II: High Dose Benfotiamine Experimental Treatment 1 Intervention

Participants will take 600mg benfotiamine capsules twice a day (BID; once in the morning and once in the evening).

Group III: Placebo Placebo Group 1 Intervention

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.

Benfotiamine is already approved in European Union, United States, India, Japan for the following indications:

Approved in European Union as Benfotiamine for:

• Dietary Supplementation
• Diabetic Neuropathy

Approved in United States as Benfotiamine for:

• Dietary Supplementation

Approved in India as Benfotiamine for:

• Dietary Supplementation
• Diabetic Neuropathy
• Neuropathic Pain

Approved in Japan as Benfotiamine for:

• Dietary Supplementation
• Diabetic Neuropathy

Who Is Running the Clinical Trial?

Alzheimer's Disease Cooperative Study (ADCS)

Lead Sponsor

Trials

25

Recruited

6,400+

Burke Medical Research Institute

Collaborator

Trials

24

Recruited

1,500+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

Anticholinesterase drugs, such as donepezil and rivastigmine, provide significant cognitive benefits for patients with mild-to-moderate Alzheimer's disease, although they can cause side effects in 5% to 15% of cases, including nausea and dizziness.

Memantine, an NMDA receptor antagonist, offers an alternative treatment for moderately severe to severe Alzheimer's disease by protecting neurons from harmful glutamate activity while supporting normal neurotransmitter function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of cognitive impairment in Alzheimer's disease. Burns, A.[2021]

Donepezil, rivastigmine, and galantamine are new cholinesterase inhibitors that work by inhibiting the enzyme AChE, which is important for treating Alzheimer's disease.

Rivastigmine's ability to also inhibit BuChE may provide extra benefits for patients in late stages of Alzheimer's, although it could lead to more gastrointestinal side effects, while galantamine's role as an allosteric modulator of nicotinic receptors may enhance attention and other behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The new cholinesterase inhibitors for Alzheimer's disease, Part 1: their similarities are different. Stahl, SM.[2019]

Rivastigmine is a centrally-selective acetylcholinesterase inhibitor that has been shown to significantly improve cognition and daily living activities in Alzheimer's patients, with effective doses ranging from 6 to 12 mg/day.

The drug is generally well-tolerated, with common side effects like nausea and dizziness that can be managed through gradual dose increases, and it has minimal drug interactions due to its limited metabolism by the cytochrome P450 system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rivastigmine, a brain-region selective acetylcholinesterase inhibitor for treating Alzheimer's disease: review and current status. Gottwald, MD., Rozanski, RI.[2019]

In a 12-month trial involving 70 participants with amnestic mild cognitive impairment or mild Alzheimer's disease, benfotiamine was found to be safe and showed a trend towards less cognitive decline compared to placebo, with a 43% lower increase in cognitive impairment scores.

Benfotiamine significantly reduced the worsening of dementia ratings by 77% and decreased levels of advanced glycation end products, suggesting it may have a beneficial effect on cognitive function, especially in individuals who do not carry the APOEɛ4 gene associated with Alzheimer's risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benfotiamine and Cognitive Decline in Alzheimer's Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial. Gibson, GE., Luchsinger, JA., Cirio, R., et al.[2021]

Current pharmacological treatments for Alzheimer's disease primarily focus on providing temporary symptomatic relief, with options like acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine available for managing cognitive symptoms and neuropsychiatric issues.

Despite ongoing research into disease-modifying therapies targeting the amyloid pathway, no significant breakthroughs have been achieved yet, highlighting the challenges in developing effective long-term treatments for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[From symptomatic to disease modifying therapy? Recent developments in the pharmacotherapy of Alzheimer's disease]. Franke, AG., Lieb, K., Fellgiebel, A.[2009]

Galantamine, rivastigmine, and memantine are now covered by national health insurance in Japan for treating Alzheimer-type dementia, with galantamine and rivastigmine acting as choline esterase inhibitors and memantine as a glutamate NMDA receptor antagonist, providing a multi-faceted approach to treatment.

These medications not only target cognitive symptoms but also help manage behavioral and psychological symptoms of dementia (BPSD), with memantine specifically reducing aggressiveness and excitement, highlighting the importance of tailored treatment strategies based on individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness and limitation of newly approved drugs for Alzheimer's disease]. Hattori, H.[2015]

Long-term administration of benfotiamine (300 mg daily for 18 months) led to cognitive improvements in five patients with mild to moderate Alzheimer's disease, as measured by the Mini-Mental Status Examination (MMSE), with an average increase of 3.2 points.

The cognitive benefits observed with benfotiamine occurred independently of changes in brain amyloid levels, suggesting a potential new avenue for disease-modifying therapies in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Cognitive Improvement After Benfotiamine Administration in Patients with Alzheimer's Disease. Pan, X., Chen, Z., Fei, G., et al.[2018]

Rivastigmine is an effective treatment for mild-to-moderate Alzheimer's disease, showing significant improvements in cognition and global functioning in randomized trials lasting up to 6 months, with potential benefits lasting up to 5 years.

The most common side effects are gastrointestinal issues, which can be managed by adjusting the dosage schedule and taking the medication with food, allowing for safer and more effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rivastigmine for Alzheimer's disease. Desai, AK., Grossberg, GT.[2019]

Citations

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Benfotiamine and Cognitive Decline in Alzheimer's Disease

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goizuetabrainhealth.emory.edu

goizuetabrainhealth.emory.edu/news/early-alzheimers-clinical-trial.html

Recruiting people with early Alzheimer's Disease for a clinical ...

Previous research from a 12-month, single-site pilot trial in people with early AD demonstrated that benfotiamine was safe and well tolerated, ...

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news.uhhospitals.org

news.uhhospitals.org/news-releases/articles/2025/04/uh-recruiting-people-with-early-ad-for-a-clinical-trial-evaluating-benfotiamine

UH Cleveland Medical Center Currently Recruiting People ...

For example, the increase in the Alzheimer's Disease Assessment Scale-Cognitive Subscale was 43% lower in the benfotiamine group than in the ...

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clinicaltrials.gov/study/NCT06223360

NCT06223360 | A Trial to Evaluate the Safety and Efficacy ...

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 ...

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clinicaltrials.cedars-sinai.edu

clinicaltrials.cedars-sinai.edu/view/ADC-061-BENFO

Benfotiamine in Patients With Early Alzheimer's Disease

The purpose of this study is to evaluate the safety and effectiveness of an experimental drug called benfotiamine as a possible treatment for Alzheimer's.

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alzdiscovery.org/uploads/cognitive_vitality_media/Benfotiamine.pdf

Benfotiamine.pdf

Neuroprotective Benefit: Benfotiamine showed a trend for slowing cognitive decline in. MCI/AD while also decreasing levels of AGEs. Benefits may ...

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pubmed.ncbi.nlm.nih.gov

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Benfotiamine and Cognitive Decline in Alzheimer's Disease

Oral benfotiamine is safe and potentially efficacious in improving cognitive outcomes among persons with MCI and mild AD.