Alzheimer's DiseasePhase 2BenfotiamineNCT02292238
Benfotiamine in Alzheimer's Disease: A Pilot Study
A Phase 2 study testing Benfotiamine in people with Alzheimer's Disease, run by Burke Medical Research Institute at 1 site in United States.
Trial summary
General Investigational Plan Study Objectives The goal of this proposal is to determine whether enhancing brain glucose utilization minimizes cognitive decline in patients with Amnestic Mild Cognitive Impairment (AMCI) or mild Alzheimer's disease (AD) dementia. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Benfotiamine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 71 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2015to 8 Sep 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 60 years of age or older
- Clinical diagnosis of AMCI by the Peterson criteria or probable AD dementia according to the National Institute of Neurological Disorders and stroke and the Alzheimer's Disease related Disorders Association (NINCDS/ADRDA)
- MMSE score > or equal to 21
- CDR score > or equal to 0.5 and < or equal to1
- Cornell Scale for Depression in Dementia(CSDD) score <10.
- Ambulatory or ambulatory with aide
Show all 12Show fewer
- Have a caregiver willing to accompany the patient to each visit, accept responsibility for supervising treatment and provided input to clinical outcome assessments
- Reside at home
- Speak English
- Amyloid positive PET-scan
- If they are on AD medications they must be stable on AD medications for at least three months prior to baseline
- Subjects ore willing/able to provide informed consent.
Who cannot join
- Patients with significant neurological disorder other than AD including hypoxia, stroke, traumatic brain injury
- A current psychiatric disorder according the DSM-IV diagnosis of major depression unless successfully treated on a stable dose of an antidepressant for at least 4 weeks and continues on stable dose throughout the study
- Any other DSM-IV Axis l diagnosis including other primary neurodegenerative dementia schizophrenia or bipolar depression
- A current diagnosis of uncontrolled diabetes mellitus (glucose values > 200 mg/ml).
- Patients with uncontrolled diabetes will be excluded because high glucose will alter the FDG-PET studies. The clinic that does PET (Columbia University Medical Center) excludes patients if glucose values exceed 200 mg/ml.
- A current diagnosis of active, uncontrolled seizure disorder
Show all 15Show fewer
- A current diagnosis of probable or possible vascular dementia according to NINDS-AIREN
- An investigational drug during the previous 4 weeks
- A current diagnosis of severe unstable cardiovascular disease
- A current diagnosis of acute severe, or unstable asthmatic condition (e.g., severe chronic obstructive pulmonary disease (COPD),
- A current diagnosis of cardiac, renal or hepatic disease
- History of alcoholism, current or within past 5 years
- A disability that may prevent the patient from completing all study requirements (e.g., blindness, deafness, severe language difficulty)
- A1C less than or equal to 8
- Current diagnosis of cancer/active treatments
Trial locations and contacts
1 site in 1 country.
About this study
General Investigational Plan
Study Objectives The goal of this proposal is to determine whether enhancing brain glucose utilization minimizes cognitive decline in patients with Amnestic Mild Cognitive Impairment (AMCI) or mild Alzheimer's disease (AD) dementia. We propose a proof of concept double-blind, placebo controlled pilot study to determine if increasing brain thiamine availability with the investigational new drug benfotiamine, will minimize the decline in glucose utilization and slow the cognitive decline associated with the progression AMCI/AD dementia.
Read more
Specifically, our objectives are two-fold:
- 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.
We will also carry out the following secondary objectives:
- Assess if there are differences in secondary clinical outcome measures (NPI, ADCSADL, CDR, Buschke) between benfotiamine and placebo groups and whether specific cognitive domains (ie: activities of daily living, learning and memory verbal memory, behavioral, etc.) are driving these changes.
- Compare ADAS-COG change scores in the benfotiamine and placebo groups within and between strata that were defined by initial cognitive impairment, to attempt to identified the population that most benefits from benfotiamine.
- Compare changes in glucose utilization between the benfotiamine and placebo groups in secondary Regions of Interest (ROIs) including the hippocampus, prefrontal regions and entorhinal cortex.
- Compare changes in whole brain glucose utilization between the benfotiamine and placebo groups using statistical parametric mapping (SPM).
- Assess the correlation between changes in glucose utilization with changes in ADAS Cog.
- Determine if ApoE4 genotype alters the response to benfotiamine.
Read the detailed description
Study Design
This study will be conducted at the Burke Rehabilitation Hospital under an IRB protocol. Wplan to accrue a total of 76 male and/or female patients (> 65 years) with a diagnosis of AMCI/AD dementia that are also amyloid positive by PET scan. Patients will be randomized and blinded to either a benfotiamine or placebo group. Because it is unknown whether there will be differential responses to treatment according to initial cognitive impairment, participants will be stratified according to the median MMSE cut-off score of our historical METS population who are > 65 years old and have an MMSE >21.
In this double-blind study, patients and their caregivers, as well as all physicians, clinicians, coordinators and investigators interacting with the patients, will be unaware of the treatment assignments. Treatment assignments will be available to the safety-monitoring physician, Dr. Michael Reding, who will have no unnecessary subject contact. If necessary, the code will be revealed to Dr. Reding by the pharmacist, Dr. Thomas Grandville.
Each patient will make six visits to the Memory Evaluation and Treatment Service (METS) clinic at Burke Rehabilitation Hospital. Information on medication use, vital signs, outcome measures, compliance and safety/tolerability will be collected at each time point. The screening visit (visit 1) will take place within 30 days prior to baseline visit (visit 2). Informed consent/assent will be obtained from each subject or his/her caregiver prior to conducting any study related procedures. During the screening visit a review of inclusion/exclusion criteria will be completed along with the collection of demographic data, disease history, and information about prior and concomitant medications. A complete medical history, physical examination, neurological examination, including the MMSE, CDR, CSDD and vital signs, will be collected. Blood will be drawn to assess blood glucose Patients that are diagnosed as likely Alzheimer patients that are not hyperglycemic will then have an amyloid PET scan. Only patients with a diagnosis of AD and a positive amyloid scan will be included. Prior to baseline (visit 2), FDGPET studies will be completed for each subject. At the baseline visit (visit 2) blood will be drawn to determine APOE and thiamine (vitamin B1 status). At visits 2-6, information on concomitant medications will be updated, vitals will be taken, medication compliance will be assessed and the following study measures will be administered: Alzheimer's Disease Assessment Scale (ADASCog), Buschke SRT, Neuropsychological Inventory (NPI), Clinical Dementia Rating Scale (CDR) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADLs). The final PET scan will be conducted approximately one week prior to the last visit. In addition to safety assessments at time of each visit, each patient will receive a call from the clinical coordinator at weeks 2 and 6 to assess for adverse events.
The benfotiamine and placebo will be dispensed by the pharmacy at Burke under the direction of Thomas Grandville, D. Pharm. The caregiver will administer the drug since patients with memory problems may forget to take it on a regular basis. In the placebo group, the active compound benfotiamine will be replaced with microcrystalline cellulose. The other components, shape and color are identical to the treatment. Caregivers will be instructed to oversee the administration of the study medication as prescribed to ensure compliance. A record of the number of capsules dispensed, number returned, and actual number taken will be recorded at scheduled visits. Each patient will be treated for 12 months.
The study cognitive measures include: the ADAS-Cog (our primary outcome measure), Alzheimer's Disease Cooperative Study-Activities of Daily Living, Neuropsychiatric Inventory, Clinical Dementia Rating Scale, Buschke Selective Reminding Test (SRT). is a standard diagnostic tool in the assessment of verbal memory. The Biological/Mechanistic Outcome Measures will be FDG-PET Scanning Procedures
Data Analysis Preliminary analyses will be conducted to describe the study sample and to confirm the relationship between level of glucose utilization and severity of cognitive impairment. For continuous variables (eg cognitive function, glucose utilization), we will first examine distributions to assess normality assumptions. We will perform transformations as needed to stabilize the variance, and to reduce skewness and kurtosis. We will use means (sd) and proportions n (%) to characterize the study sample. T-tests and Chi-square, or Wilcoxon rank sum test and Fisher, where appropriate, will be used to assess for any differences in patient characteristics according to treatment group. We will use spearman correlation coefficients and linear regression, unadjusted and adjusted for covariates, to assess the relationship between FDG-PET and MMSE in the whole population as well as in MMSE stratified groups to examine the relationship between initial MMSE score and glucose uptake.
All analyses to test study hypotheses will be run as intention to treat (ITT). Missing observations will be addressed by using the method of last observation carried forward (LOCF).
- Conditions
- Alzheimer's Disease
- Being tested
- Benfotiamine
- Keywords
- Alzheimer's disease, benfotiamine, glucose, Amyloid
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BenfotiamineDrug
Also called S-[2-{[(4-amino-2- methylpyrimidin-5-yl)methyl] (formyl)amino}-5-(phosphonooxy)pent-2-en-3-yl] benzenecarbothioate
- 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.
| Study group | Role | What they receive |
|---|---|---|
| Benfotiamine | Experimental | The patients in this arm will be treated with benfotiamine Receives: Drug: Benfotiamine |
| Placebo | Placebo comparator | The patients in this arm will be treated with placebo Receives: Drug: Benfotiamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in ADAS-Cog Score
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.
Measured: Baseline, 1 year
Secondary outcomes (5)
Change From Baseline in Brain Glucose Utilization
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.
Measured: Baseline, 1 year
Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score
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.
Measured: Baseline, 1 year
Change From Baseline in Neuropsychiatric Inventory (NPI) Score
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.
Measured: Baseline, 1 year
Change From Baseline in Clinical Dementia Rating (CDR) Score
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.
Measured: Baseline, 1 year
Change From Baseline in Buschke Selective Reminding Test (SRT) Score
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.
Measured: Baseline, 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2014 (estimated)
- Study start15 Feb 2015
- Primary completion20 Jul 2020
- Study completion8 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Burke Medical Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Burke Rehabilitation Hospital, Columbia University, National Institute on Aging (NIA), Alzheimer's Drug Discovery Foundation, Montefiore Medical Center
- Responsible party
- Principal investigator, Gary E. Gibson, Burke Medical Research Institute
- Investigators
- Gary E Gibson, Ph.D., Principal investigator, Burke Medical Research InstitutePasquale Fonzetti, MD, PhD, Principal investigator, Burke Rehabilitation Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02292238
- Sponsor's protocol ID
- BRC-451
- Other IDs
- 1R01AG043679-01A1
- Acronym
- Benfotiamine
- Status last verified
- Jun 2022
- First submitted
- 10 Nov 2014
- Last updated
- 28 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 33074237
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Benfotiamine in Alzheimer's Disease: A Pilot Study
- ClinicalTrials.gov ID
- NCT02292238
- Acronym / sponsor ID
- Benfotiamine / BRC-451
- Conditions
- Alzheimer's Disease
- Keywords
- Alzheimer's disease, benfotiamine, glucose, Amyloid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Burke Medical Research InstituteUniversity, hospital or other
- Collaborators
- Burke Rehabilitation Hospital, Columbia University, National Institute on Aging (NIA), Alzheimer's Drug Discovery Foundation, Montefiore Medical Center
- Study start
- 15 Feb 2015 (actual)
- Primary completion
- 20 Jul 2020 (actual)
- Study completion
- 8 Sep 2020 (actual)
- First posted
- 17 Nov 2014 (estimated)
- Results
- Posted 28 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
General Investigational Plan
Study Objectives The goal of this proposal is to determine whether enhancing brain glucose utilization minimizes cognitive decline in patients with Amnestic Mild Cognitive Impairment (AMCI) or mild Alzheimer's disease (AD) dementia. We propose a proof of concept double-blind, placebo controlled pilot study to determine if increasing brain thiamine availability with the investigational new drug benfotiamine, will minimize the decline in glucose utilization and slow the cognitive decline associated with the progression AMCI/AD dementia.
Specifically, our objectives are two-fold:
- 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.
We will also carry out the following secondary objectives:
- Assess if there are differences in secondary clinical outcome measures (NPI, ADCSADL, CDR, Buschke) between benfotiamine and placebo groups and whether specific cognitive domains (ie: activities of daily living, learning and memory verbal memory, behavioral, etc.) are driving these changes.
- Compare ADAS-COG change scores in the benfotiamine and placebo groups within and between strata that were defined by initial cognitive impairment, to attempt to identified the population that most benefits from benfotiamine.
- Compare changes in glucose utilization between the benfotiamine and placebo groups in secondary Regions of Interest (ROIs) including the hippocampus, prefrontal regions and entorhinal cortex.
- Compare changes in whole brain glucose utilization between the benfotiamine and placebo groups using statistical parametric mapping (SPM).
- Assess the correlation between changes in glucose utilization with changes in ADAS Cog.
- Determine if ApoE4 genotype alters the response to benfotiamine.
Detailed description
Study Design
This study will be conducted at the Burke Rehabilitation Hospital under an IRB protocol. Wplan to accrue a total of 76 male and/or female patients (> 65 years) with a diagnosis of AMCI/AD dementia that are also amyloid positive by PET scan. Patients will be randomized and blinded to either a benfotiamine or placebo group. Because it is unknown whether there will be differential responses to treatment according to initial cognitive impairment, participants will be stratified according to the median MMSE cut-off score of our historical METS population who are > 65 years old and have an MMSE >21.
In this double-blind study, patients and their caregivers, as well as all physicians, clinicians, coordinators and investigators interacting with the patients, will be unaware of the treatment assignments. Treatment assignments will be available to the safety-monitoring physician, Dr. Michael Reding, who will have no unnecessary subject contact. If necessary, the code will be revealed to Dr. Reding by the pharmacist, Dr. Thomas Grandville.
Each patient will make six visits to the Memory Evaluation and Treatment Service (METS) clinic at Burke Rehabilitation Hospital. Information on medication use, vital signs, outcome measures, compliance and safety/tolerability will be collected at each time point. The screening visit (visit 1) will take place within 30 days prior to baseline visit (visit 2). Informed consent/assent will be obtained from each subject or his/her caregiver prior to conducting any study related procedures. During the screening visit a review of inclusion/exclusion criteria will be completed along with the collection of demographic data, disease history, and information about prior and concomitant medications. A complete medical history, physical examination, neurological examination, including the MMSE, CDR, CSDD and vital signs, will be collected. Blood will be drawn to assess blood glucose Patients that are diagnosed as likely Alzheimer patients that are not hyperglycemic will then have an amyloid PET scan. Only patients with a diagnosis of AD and a positive amyloid scan will be included. Prior to baseline (visit 2), FDGPET studies will be completed for each subject. At the baseline visit (visit 2) blood will be drawn to determine APOE and thiamine (vitamin B1 status). At visits 2-6, information on concomitant medications will be updated, vitals will be taken, medication compliance will be assessed and the following study measures will be administered: Alzheimer's Disease Assessment Scale (ADASCog), Buschke SRT, Neuropsychological Inventory (NPI), Clinical Dementia Rating Scale (CDR) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADLs). The final PET scan will be conducted approximately one week prior to the last visit. In addition to safety assessments at time of each visit, each patient will receive a call from the clinical coordinator at weeks 2 and 6 to assess for adverse events.
The benfotiamine and placebo will be dispensed by the pharmacy at Burke under the direction of Thomas Grandville, D. Pharm. The caregiver will administer the drug since patients with memory problems may forget to take it on a regular basis. In the placebo group, the active compound benfotiamine will be replaced with microcrystalline cellulose. The other components, shape and color are identical to the treatment. Caregivers will be instructed to oversee the administration of the study medication as prescribed to ensure compliance. A record of the number of capsules dispensed, number returned, and actual number taken will be recorded at scheduled visits. Each patient will be treated for 12 months.
The study cognitive measures include: the ADAS-Cog (our primary outcome measure), Alzheimer's Disease Cooperative Study-Activities of Daily Living, Neuropsychiatric Inventory, Clinical Dementia Rating Scale, Buschke Selective Reminding Test (SRT). is a standard diagnostic tool in the assessment of verbal memory. The Biological/Mechanistic Outcome Measures will be FDG-PET Scanning Procedures
Data Analysis Preliminary analyses will be conducted to describe the study sample and to confirm the relationship between level of glucose utilization and severity of cognitive impairment. For continuous variables (eg cognitive function, glucose utilization), we will first examine distributions to assess normality assumptions. We will perform transformations as needed to stabilize the variance, and to reduce skewness and kurtosis. We will use means (sd) and proportions n (%) to characterize the study sample. T-tests and Chi-square, or Wilcoxon rank sum test and Fisher, where appropriate, will be used to assess for any differences in patient characteristics according to treatment group. We will use spearman correlation coefficients and linear regression, unadjusted and adjusted for covariates, to assess the relationship between FDG-PET and MMSE in the whole population as well as in MMSE stratified groups to examine the relationship between initial MMSE score and glucose uptake.
All analyses to test study hypotheses will be run as intention to treat (ITT). Missing observations will be addressed by using the method of last observation carried forward (LOCF).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Benfotiamine | Experimental | Drug: BenfotiamineThe patients in this arm will be treated with benfotiamine |
| Placebo | Placebo comparator | Drug: BenfotiamineThe patients in this arm will be treated with placebo |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 60 years of age or older
- Clinical diagnosis of AMCI by the Peterson criteria or probable AD dementia according to the National Institute of Neurological Disorders and stroke and the Alzheimer's Disease related Disorders Association (NINCDS/ADRDA)
- MMSE score > or equal to 21
- CDR score > or equal to 0.5 and < or equal to1
- Cornell Scale for Depression in Dementia(CSDD) score <10.
Key exclusion criteria (15 listed)
- Patients with significant neurological disorder other than AD including hypoxia, stroke, traumatic brain injury
- A current psychiatric disorder according the DSM-IV diagnosis of major depression unless successfully treated on a stable dose of an antidepressant for at least 4 weeks and continues on stable dose throughout the study
- Any other DSM-IV Axis l diagnosis including other primary neurodegenerative dementia schizophrenia or bipolar depression
- A current diagnosis of uncontrolled diabetes mellitus (glucose values > 200 mg/ml).
- Patients with uncontrolled diabetes will be excluded because high glucose will alter the FDG-PET studies. The clinic that does PET (Columbia University Medical Center) excludes patients if glucose values exceed 200 mg/ml.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BenfotiamineAlso: S-[2-{[(4-amino-2- methylpyrimidin-5-yl)methyl] (formyl)amino}-5-(phosphonooxy)pent-2-en-3-yl] benzenecarbothioate* 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. | Drug | Benfotiamine, Placebo |
Primary outcome
Change From Baseline in ADAS-Cog Score
Time frame: Baseline, 1 year
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.
5 secondary outcomes
Change From Baseline in Brain Glucose Utilization
Time frame: Baseline, 1 year
Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score
Time frame: Baseline, 1 year
Change From Baseline in Neuropsychiatric Inventory (NPI) Score
Time frame: Baseline, 1 year
Change From Baseline in Clinical Dementia Rating (CDR) Score
Time frame: Baseline, 1 year
Change From Baseline in Buschke Selective Reminding Test (SRT) Score
Time frame: Baseline, 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 33074237Gibson 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.
Related trials for Alzheimer's Disease
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
RecruitingObservational study
Effectiveness and Safety of Disease-Modifying Therapy for Alzheimer's Disease: A Multicenter Retrospective Study
Alzheimer's Disease (AD)
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingPhase 3
A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease
Alzheimer's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary E Gibson, Ph.D. principal investigator
Burke Medical Research Institute
Pasquale Fonzetti, MD, PhD principal investigator
Burke Rehabilitation Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Benfotiamine in people with Alzheimer's Disease, run by Burke Medical Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in ADAS-Cog Score (time frame: Baseline, 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02292238, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2022.