Trial Outcomes & Findings for Benfotiamine in Alzheimer's Disease: A Pilot Study (NCT NCT02292238)

NCT ID: NCT02292238

Last Updated: 2022-06-28

Results Overview

The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is a brief neuropsychological assessment used to assess the severity of cognitive symptoms of dementia. It is one of the most widely used cognitive scales in clinical trials and is considered to be the "gold standard" for assessing antidementia treatments. The ADAS-Cog range from 0 to 70, where higher scores indicate greater cognitive dysfunction.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 71 participants
• Primary outcome timeframe: Baseline, 1 year
• Results posted on: 2022-06-28

Participant Flow

All patients were recruited from the Memory Evaluation and Treatment Service at the Burke Rehabilitation Center.

Participant milestones

Measure	Benfotiamine The patients in this arm will be treated with benfotiamine Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.	Placebo The patients in this arm will be treated with placebo To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients. Placebo group received identical capsules without benfotiamine
Overall Study STARTED	34	37
Overall Study COMPLETED	30	33
Overall Study NOT COMPLETED	4	4

Reasons for withdrawal

Measure	Benfotiamine The patients in this arm will be treated with benfotiamine Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.	Placebo The patients in this arm will be treated with placebo To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients. Placebo group received identical capsules without benfotiamine
Overall Study Protocol Violation	1	2
Overall Study Withdrawal by Subject	2	1
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	0	1

Baseline Characteristics

Benfotiamine in Alzheimer's Disease: A Pilot Study

Baseline characteristics by cohort

Measure	Benfotiamine n=34 Participants The patients in this arm will be treated with benfotiamine Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.	Placebo n=36 Participants The patients in this arm will be treated with placebo Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.	Total n=70 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	34 Participants n=5 Participants	36 Participants n=7 Participants	70 Participants n=5 Participants
Age, Continuous	75.74 years STANDARD_DEVIATION 6.91 • n=5 Participants	75.81 years STANDARD_DEVIATION 7.19 • n=7 Participants	75.77 years STANDARD_DEVIATION 7.01 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	18 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	18 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	33 Participants n=5 Participants	35 Participants n=7 Participants	68 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	34 Participants n=5 Participants	36 Participants n=7 Participants	70 Participants n=5 Participants
MMSE Scores	25.32 scores on a scale STANDARD_DEVIATION 2.78 • n=5 Participants	25.33 scores on a scale STANDARD_DEVIATION 2.52 • n=7 Participants	25.33 scores on a scale STANDARD_DEVIATION 2.63 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 1 year

Population: 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.

The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is a brief neuropsychological assessment used to assess the severity of cognitive symptoms of dementia. It is one of the most widely used cognitive scales in clinical trials and is considered to be the "gold standard" for assessing antidementia treatments. The ADAS-Cog range from 0 to 70, where higher scores indicate greater cognitive dysfunction.

Outcome measures

Measure	Benfotiamine n=34 Participants The patients in this arm will be treated with benfotiamine Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.	Placebo n=36 Participants The patients in this arm will be treated with placebo Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.
Change From Baseline in ADAS-Cog Score	1.39 score on a scale Standard Deviation 5.63	3.26 score on a scale Standard Deviation 5.52

SECONDARY outcome

Timeframe: Baseline, 1 year

Population: 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.

The AAL (Automatic Anatomical Labeling) atlas provides the taxonomy for 116 regions of interest, 90 of which capture non-cerebellar cortical regions. Signal averages from 9 cerebellar regions from each hemisphere were further averaged into one composite cerebellar region for each hemisphere, 'Cerebellum_L' and 'Cerebellum_R', which were comprised of the respective laterality averages of the regions: 'Cerebellum_Crus1 ' 'Cerebellum_Crus2 'Cerebellum_3' 'Cerebellum_4_5' 'Cerebellum_6' 'Cerebellum_7b' 'Cerebellum_8' 'Cerebellum_9' 'Cerebellum_10 '. Subsequently, these two composite regions are further combined with the bilateral paracentral lobules to provide one final composite for reference scaling. Concretely, the values from 'Cerebellum_L', 'Cerebellum_R', 'Paracentral_Lobule_L', and 'Paracentra_Lobule_R' were averaged. This final composite will serve as the denominator for the scaling operation of any ROI value prior to group-level analysis.

Outcome measures

Measure	Benfotiamine n=34 Participants The patients in this arm will be treated with benfotiamine Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.	Placebo n=36 Participants The patients in this arm will be treated with placebo Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.
Change From Baseline in Brain Glucose Utilization	-0.02 ratio Standard Error 0.02	-0.01 ratio Standard Error 0.002

SECONDARY outcome

Timeframe: Baseline, 1 year

Population: 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.

Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) is a caregiver-based Activities of Daily Living (ADL) scale composed of 23 items developed for use in dementia clinical studies. It was designed to assess the patient's performance of both basic and instrumental activities of daily living such as those necessary for personal care, communicating and interacting with other people, maintaining a household, conducting hobbies and interests, as well as making judgments and decisions. The range for the total ADCS-ADL score is 0 to 78. Higher scores equate with higher functioning.

Outcome measures

Measure	Benfotiamine n=34 Participants The patients in this arm will be treated with benfotiamine Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.	Placebo n=36 Participants The patients in this arm will be treated with placebo Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.
Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score	-1.931 score on a scale Standard Deviation 0.9028	-3.16129 score on a scale Standard Deviation 0.9816

SECONDARY outcome

Timeframe: Baseline, 1 year

Population: 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.

The NPI assesses a wide range of behaviors encountered in dementia patients to provide a means of distinguishing frequency and severity of behavioral changes. Ten behavioral and two neuro-vegetative domains are evaluated through an interview with the caregiver. The total score ranges from 0 to 144. Higher scores suggest greater psychiatric impairment.

Outcome measures

Measure	Benfotiamine n=34 Participants The patients in this arm will be treated with benfotiamine Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.	Placebo n=36 Participants The patients in this arm will be treated with placebo Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.
Change From Baseline in Neuropsychiatric Inventory (NPI) Score	6.69 score on a scale Standard Deviation 2.29	9.23 score on a scale Standard Deviation 3.8

SECONDARY outcome

Timeframe: Baseline, 1 year

Population: 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.

The CDR was developed primarily for use in persons with dementia of the Alzheimer type (the equivalent of probable Alzheimer's Disease) and can also be used to stage dementia in other illnesses as well. The scores for the multiple items are summarized in one score. The CDR examines 6 categories of cognitive functioning domains. Each domain is scored on a scale ranging from 0 to 3 (including 0.5). A CDR-SB was generated as the sum of the values in each of the 6 domains. The CDR-SB sum scores range from 0 to 18, with higher scores indicating greater cognitive impairment and a 1 point worsening is considered a clinically significant symptom change.

Outcome measures

Measure	Benfotiamine n=34 Participants The patients in this arm will be treated with benfotiamine Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.	Placebo n=36 Participants The patients in this arm will be treated with placebo Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.
Change From Baseline in Clinical Dementia Rating (CDR) Score	0.05 score on a scale Standard Deviation 0.08	0.22 score on a scale Standard Deviation 0.06

SECONDARY outcome

Timeframe: Baseline, 1 year

Population: 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.

The SRT is a standard diagnostic tool in the assessment of verbal memory. The Buschke SRT immediate total scores are compared between treated (benfotiamine) and control (placebo) groups. The immediate total score is the sum of correct responses over the 6 learning trials with scores ranging from 0 to 72. A score of 0 means severe impairment in memory. A score of 72 means there is no impairment in memory. For the purpose of determining effect over several trials between groups, the fractional change from the baseline of each group is compared.

Outcome measures

Measure	Benfotiamine n=34 Participants The patients in this arm will be treated with benfotiamine Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.	Placebo n=36 Participants The patients in this arm will be treated with placebo Benfotiamine: • To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients as measured with Fluorodeoxyglucose Positron Emission Tomography(FGPET) in the posterior cingulate.
Change From Baseline in Buschke Selective Reminding Test (SRT) Score	0.86 score on a scale Standard Deviation 1.1	-1.12 score on a scale Standard Deviation 1

Adverse Events

Benfotiamine

Serious events: 3 serious events

Other events: 25 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Measure	Benfotiamine n=34 participants at risk To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients. Placebo group received identical capsules without benfotiamine	Placebo n=36 participants at risk The patients in this arm will be treated with placebo To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients. Placebo group received identical capsules without benfotiamine
General disorders Surgery	2.9% 1/34 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.	8.3% 3/36 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.
General disorders Stroke	5.9% 2/34 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.	0.00% 0/36 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.

Other adverse events

Measure	Benfotiamine n=34 participants at risk To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients. Placebo group received identical capsules without benfotiamine	Placebo n=36 participants at risk The patients in this arm will be treated with placebo To test whether increasing brain thiamine by administering 600 mg per day (300 mg/morning and 300 mg/evening) of benfotiamine for one year can slow cognitive decline in these patients as measured with the Alzheimer's Disease Assessment Scale (ADAS-COG). • To determine whether increasing brain thiamine availability with 600 mg (300 mg/morning and 300 mg/evening) per day of benfotiamine for one year can slow the decline in brain glucose metabolism in these patients. Placebo group received identical capsules without benfotiamine
Psychiatric disorders Anxiety	14.7% 5/34 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.	11.1% 4/36 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.
Skin and subcutaneous tissue disorders Bruise	5.9% 2/34 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.	13.9% 5/36 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.
Respiratory, thoracic and mediastinal disorders Cold Symptoms	8.8% 3/34 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.	8.3% 3/36 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.
Psychiatric disorders Depression	2.9% 1/34 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.	5.6% 2/36 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.
Ear and labyrinth disorders Dizziness	8.8% 3/34 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.	8.3% 3/36 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.
Injury, poisoning and procedural complications Fall	17.6% 6/34 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.	33.3% 12/36 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.
Injury, poisoning and procedural complications Head Injury	0.00% 0/34 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.	5.6% 2/36 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.
Cardiac disorders Heart Arrhythmia	2.9% 1/34 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.	5.6% 2/36 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.
Nervous system disorders Pain	14.7% 5/34 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.	11.1% 4/36 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/34 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.	8.3% 3/36 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.
Injury, poisoning and procedural complications Sprain	0.00% 0/34 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.	5.6% 2/36 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.
General disorders Allergy	0.00% 0/34 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.	5.6% 2/36 • 1 year 1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.

Additional Information

Gary E Gibson, Professor of Neuroscience

Weill Cornell Med/ Burke Neurological Institute

Phone: 9145972291

Email: ggibson@med.cornell.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place