Benfotiamine in Alzheimer's Disease: A Pilot Study (Benfotiamine)

• ClinicalTrials.gov Identifier: NCT02292238
• Recruitment Status: Completed
• First Posted: November 17, 2014
• Results First Posted: June 28, 2022
• Last Update Posted: June 28, 2022
• Sponsor: Burke Medical Research Institute
• Collaborators: Burke Rehabilitation Hospital; Columbia University; National Institute on Aging (NIA); Alzheimer's Drug Discovery Foundation; Montefiore Medical Center
• Information provided by (Responsible Party): Gary E. Gibson, Burke Medical Research Institute

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alzheimer's Disease
• Intervention: Drug: Benfotiamine
• Enrollment: 71

Participant Flow

Recruitment Details	All patients were recruited from the Memory Evaluation and Treatment Service at the Burke Rehabilitation Center.
Pre-assignment Details

Arm/Group Title	Benfotiamine	Placebo
Arm/Group Description	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.	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
Period Title: Overall Study
Started	34	37
Completed	30	33
Not Completed	4	4
Reason Not Completed
Protocol Violation	1	2
Withdrawal by Subject	2	1
Lost to Follow-up	1	0
Physician Decision	0	1

Baseline Characteristics

Arm/Group Title		Benfotiamine	Placebo	Total
Arm/Group Description		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.	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 of all reporting groups
Overall Number of Baseline Participants		34	36	70
Baseline Analysis Population Description		1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	34 participants	36 participants	70 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%
	>=65 years	34 100.0%	36 100.0%	70 100.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	34 participants	36 participants	70 participants
		75.74 (6.91)	75.81 (7.19)	75.77 (7.01)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	34 participants	36 participants	70 participants
	Female	23 67.6%	18 50.0%	41 58.6%
	Male	11 32.4%	18 50.0%	29 41.4%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	34 participants	36 participants	70 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 2.9%	1 2.8%	2 2.9%
	White	33 97.1%	35 97.2%	68 97.1%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment [1]; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	34 participants	36 participants	70 participants
		34 100.0%	36 100.0%	70 100.0%
		[1] Measure Description: All measures were made at patient interviews at the Burke Rehabilitation Hospital
MMSE Scores [1]; Mean (Standard Deviation); Unit of measure: Scores on a scale
	Number Analyzed	34 participants	36 participants	70 participants
		25.32 (2.78)	25.33 (2.52)	25.33 (2.63)
		[1] Measure Description: The Mini Mental State Examination (MMSE) is a set of standardized questions used to evaluate possible cognitive impairment and help stage the severity level of this impairment. Total scores on the MMSE range from 0 to 30. A total score of 0 indicates severe impairment, whereas a total score of 30 is normal. Scores of 20 to 25 are consistent with mild Alzheimer's Disease.

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in ADAS-Cog Score
Description	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.
Time Frame	Baseline, 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Benfotiamine	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	34	36
Mean (Standard Deviation); Unit of Measure: score on a scale
	1.39 (5.63)	3.26 (5.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benfotiamine, Placebo
	Comments	Power was calculated based on expected difference in change on the ADAS-Cog of 3 points between the treatment and control groups. Estimates based on using a two-sided alpha of 0.05 and a standard deviation of 4, enrolling 29 patients per group, (N = 58) suggest 80% power to detect a mean change of 3 between treatment and placebo.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.125
	Comments	Univariable (unadjusted) and a priori threshold for statistical significance is 0.05.
	Method	t-test, 2 sided
	Comments	Equal variance t-test.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.8691
	Parameter Dispersion	Type: Standard Deviation; Value: 5.5727
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Change From Baseline in Brain Glucose Utilization
Description	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.
Time Frame	Baseline, 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Benfotiamine	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	34	36
Mean (Standard Error); Unit of Measure: ratio
	-0.02 (0.02)	-0.01 (0.002)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benfotiamine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Univariable (unadjusted) and a priori threshold for statistical significance is 0.05.
Statistical Test of Hypothesis	P-Value	0.7529
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	Equal variance t-test.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.00184
	Parameter Dispersion	Type: Standard Deviation; Value: 0.0225
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score
Description	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.
Time Frame	Baseline, 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Benfotiamine	Placebo
Arm/Group Description:	Patients were treated with 600 mg/day of benfotiamine	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.
Overall Number of Participants Analyzed	34	36
Mean (Standard Deviation); Unit of Measure: score on a scale
	-1.931 (0.9028)	-3.16129 (0.9816)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benfotiamine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Univariable (unadjusted) and a priori threshold for statistical significance is 0.05.
Statistical Test of Hypothesis	P-Value	0.3687
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	Equal variance t-test.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.0636
	Parameter Dispersion	Type: Standard Deviation; Value: 4.8176
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Change From Baseline in Neuropsychiatric Inventory (NPI) Score
Description	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.
Time Frame	Baseline, 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Benfotiamine	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	34	36
Mean (Standard Deviation); Unit of Measure: score on a scale
	6.69 (2.29)	9.23 (3.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benfotiamine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4850
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	Equal variance t-test.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.8203
	Parameter Dispersion	Type: Standard Deviation; Value: 13.8988
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Change From Baseline in Clinical Dementia Rating (CDR) Score
Description	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.
Time Frame	Baseline, 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Benfotiamine	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	34	36
Mean (Standard Deviation); Unit of Measure: score on a scale
	0.05 (0.08)	0.22 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benfotiamine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0337
	Comments	The a priori threshold for statistical significance is 0.05.
	Method	t-test, 2 sided
	Comments	Equal variance t-test.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.1907
	Parameter Dispersion	Type: Standard Deviation; Value: 0.3097
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Change From Baseline in Buschke Selective Reminding Test (SRT) Score
Description	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.
Time Frame	Baseline, 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Benfotiamine	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	34	36
Mean (Standard Deviation); Unit of Measure: score on a scale
	0.86 (1.1)	-1.12 (1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benfotiamine, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Univariable (unadjusted) and a priori threshold for statistical significance is 0.05.
Statistical Test of Hypothesis	P-Value	0.315
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	Equal variance t-test.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.6161
	Parameter Dispersion	Type: Standard Deviation; Value: 5.6812
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	1 subject on the placebo arm was excluded from analysis due to taking benfotiamine from a commercial vendor.
Arm/Group Title	Benfotiamine	Placebo
Arm/Group Description	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	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
All-Cause Mortality
	Benfotiamine	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/34 (0.00%)	0/36 (0.00%)
Serious Adverse Events
	Benfotiamine	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/34 (8.82%)	3/36 (8.33%)
General disorders
Surgery †	1/34 (2.94%)	3/36 (8.33%)
Stroke †	2/34 (5.88%)	0/36 (0.00%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Benfotiamine	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	25/34 (73.53%)	23/36 (63.89%)
Cardiac disorders
Heart Arrhythmia †	1/34 (2.94%)	2/36 (5.56%)
Ear and labyrinth disorders
Dizziness †	3/34 (8.82%)	3/36 (8.33%)
General disorders
Allergy †	0/34 (0.00%)	2/36 (5.56%)
Injury, poisoning and procedural complications
Fall †	6/34 (17.65%)	12/36 (33.33%)
Head Injury †	0/34 (0.00%)	2/36 (5.56%)
Sprain †	0/34 (0.00%)	2/36 (5.56%)
Nervous system disorders
Pain †	5/34 (14.71%)	4/36 (11.11%)
Psychiatric disorders
Anxiety †	5/34 (14.71%)	4/36 (11.11%)
Depression †	1/34 (2.94%)	2/36 (5.56%)
Respiratory, thoracic and mediastinal disorders
Cold Symptoms †	3/34 (8.82%)	3/36 (8.33%)
Pneumonia †	0/34 (0.00%)	3/36 (8.33%)
Skin and subcutaneous tissue disorders
Bruise †	2/34 (5.88%)	5/36 (13.89%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Gary E Gibson, Professor of Neuroscience
• Organization: Weill Cornell Med/ Burke Neurological Institute
• Phone: 9145972291
• EMail: ggibson@med.cornell.edu

Publications of Results:

Gibson GE, Luchsinger JA, Cirio R, Chen H, Franchino-Elder J, Hirsch JA, Bettendorff L, Chen Z, Flowers SA, Gerber LM, Grandville T, Schupf N, Xu H, Stern Y, Habeck C, Jordan B, Fonzetti P. Benfotiamine and Cognitive Decline in Alzheimer's Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial. J Alzheimers Dis. 2020;78(3):989-1010. doi: 10.3233/JAD-200896.

• Responsible Party: Gary E. Gibson, Burke Medical Research Institute
• ClinicalTrials.gov Identifier: NCT02292238
• Other Study ID Numbers: BRC-451; 1R01AG043679-01A1 ( U.S. NIH Grant/Contract )
• First Submitted: November 10, 2014
• First Posted: November 17, 2014
• Results First Submitted: March 8, 2022
• Results First Posted: June 28, 2022
• Last Update Posted: June 28, 2022