Benfotiamine for Alzheimer's Disease

Recruiting at29 trial locations

Overseen by Howard Feldman, MDCM

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Alzheimer's Disease Cooperative Study (ADCS)

Must be taking: Acetylcholinesterase inhibitors, Memantine

Disqualifiers: Neurological disorders, Diabetes, Cancer, others

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

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.

What evidence supports the effectiveness of the drug Benfotiamine for Alzheimer's disease?

Research shows that long-term use of Benfotiamine improved cognitive abilities in patients with mild to moderate Alzheimer's disease, with an average increase of 3.2 points on a cognitive test after 18 months. This suggests potential benefits for brain function in Alzheimer's patients. ^{1 2 3 4 5}

How is the drug Benfotiamine unique in treating Alzheimer's disease?

Benfotiamine is unique in treating Alzheimer's disease because it is a derivative of vitamin B1 (thiamine) and may offer a novel approach by potentially addressing metabolic dysfunctions in the brain, unlike current treatments that primarily focus on neurotransmitter systems. ^{3 4 6 7 8}

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

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Benfotiamine (Anti-metabolites)

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.

Participant Groups

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 India, Japan for the following indications:

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+

Dr. Richard J. Hodes

National Institute on Aging (NIA)

Chief Executive Officer since 1993

MD from Harvard Medical School

Dr. Marie Bernard

National Institute on Aging (NIA)

Chief Medical Officer

MD from Harvard Medical School

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. Singapore pubmed.ncbi.nlm.nih.gov

Long-Term Cognitive Improvement After Benfotiamine Administration in Patients with Alzheimer's Disease. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Benfotiamine and Cognitive Decline in Alzheimer's Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial. [2021]

3. England pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Rivastigmine for Alzheimer's disease. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. Germany pubmed.ncbi.nlm.nih.gov

[From symptomatic to disease modifying therapy? Recent developments in the pharmacotherapy of Alzheimer's disease]. [2009]

8. Japan pubmed.ncbi.nlm.nih.gov

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