Asian Cohort for Alzheimer Disease (ACAD) Pilot Study: Vietnamese Americans.

INTRODUCTION: The objective of this pilot study was to establish the feasibility of recruiting older Vietnamese Americans for research addressing genetic and nongenetic risk factors for Alzheimer disease (AD). METHODS: Twenty-six Vietnamese Americans were recruited from communities in San Diego. A Community Advisory Board provided cultural and linguistic advice. Bilingual/bicultural staff measured neuropsychological, neuropsychiatric, lifestyle, and medical/neurological functioning remotely. Saliva samples allowed DNA extraction. A consensus team reviewed clinical data to determine a diagnosis of normal control (NC), mild cognitive impairment (MCI), or dementia. Exploratory analyses addressed AD risk by measuring subjective cognitive complaints (SCC), depression, and vascular risk factors (VRFs). RESULTS: Twenty-five participants completed the study (mean age=73.8 y). Eighty percent chose to communicate in Vietnamese. Referrals came primarily from word of mouth within Vietnamese communities. Diagnoses included 18 NC, 3 MCI, and 4 dementia. Participants reporting SCC acknowledged more depressive symptoms and had greater objective cognitive difficulty than those without SCC. Eighty-eight percent of participants reported at least 1 VRF. DISCUSSION: This pilot study supports the feasibility of conducting community-based research in older Vietnamese Americans. Challenges included developing linguistically and culturally appropriate cognitive and neuropsychiatric assessment tools. Exploratory analyses addressing nongenetic AD risk factors suggest topics for future study

Protocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimers disease (BenfoTeam).

BACKGROUND: Benfotiamine provides an important novel therapeutic direction in Alzheimers disease (AD) with possible additive or synergistic effects to amyloid targeting therapeutic approaches. OBJECTIVE: To conduct a seamless phase 2A-2B proof of concept trial investigating tolerability, safety, and efficacy of benfotiamine, a prodrug of thiamine, as a first-in-class small molecule oral treatment for early AD. METHODS: This is the protocol for a randomized, double-blind, placebo-controlled 72-week clinical trial of benfotiamine in 406 participants with early AD. Phase 2A determines the highest safe and well-tolerated dose of benfotiamine to be carried forward to phase 2B. During phase 2A, real-time monitoring of pre-defined safety stopping criteria in the first approximately 150 enrollees will help determine which dose (600 mg or 1200 mg) will be carried forward into phase 2B. The phase 2A primary analysis will test whether the rate of tolerability events (TEs) is unacceptably high in the high-dose arm compared to placebo. The primary safety endpoint in phase 2A is the rate of TEs compared between active and placebo arms, at each dose. The completion of phase 2A will seamlessly transition to phase 2B without pausing or stopping the trial. Phase 2B will assess efficacy and longer-term safety of benfotiamine in a larger group of participants through 72 weeks of treatment, at the selected dose. The co-primary efficacy endpoints in phase 2B are CDR-Sum of Boxes and ADAS-Cog13. Secondary endpoints include safety and tolerability measures; pharmacokinetic measures of thiamine and its esters, erythrocyte transketolase activity as blood markers of efficacy of drug delivery; ADCS-ADL-MCI; and MoCA. CONCLUSION: The BenfoTeam trial utilizes an innovative seamless phase 2A-2B design to achieve proof of concept. It includes an adaptive dose decision rule, thus optimizing exposure to the highest and best-tolerated dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06223360, registered on January 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06223360

Protocol for a seamless phase 2A-phase 2B randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of benfotiamine in patients with early Alzheimer's disease (BenfoTeam).

BACKGROUND: Benfotiamine provides an important novel therapeutic direction in Alzheimer's disease (AD) with possible additive or synergistic effects to amyloid targeting therapeutic approaches. OBJECTIVE: To conduct a seamless phase 2A-2B proof of concept trial investigating tolerability, safety, and efficacy of benfotiamine, a prodrug of thiamine, as a first-in-class small molecule oral treatment for early AD. METHODS: This is the protocol for a randomized, double-blind, placebo-controlled 72-week clinical trial of benfotiamine in 406 participants with early AD. Phase 2A determines the highest safe and well-tolerated dose of benfotiamine to be carried forward to phase 2B. During phase 2A, real-time monitoring of pre-defined safety stopping criteria in the first approximately 150 enrollees will help determine which dose (600 mg or 1200 mg) will be carried forward into phase 2B. The phase 2A primary analysis will test whether the rate of tolerability events (TEs) is unacceptably high in the high-dose arm compared to placebo. The primary safety endpoint in phase 2A is the rate of TEs compared between active and placebo arms, at each dose. The completion of phase 2A will seamlessly transition to phase 2B without pausing or stopping the trial. Phase 2B will assess efficacy and longer-term safety of benfotiamine in a larger group of participants through 72 weeks of treatment, at the selected dose. The co-primary efficacy endpoints in phase 2B are CDR-Sum of Boxes and ADAS-Cog13. Secondary endpoints include safety and tolerability measures; pharmacokinetic measures of thiamine and its esters, erythrocyte transketolase activity as blood markers of efficacy of drug delivery; ADCS-ADL-MCI; and MoCA. CONCLUSION: The BenfoTeam trial utilizes an innovative seamless phase 2A-2B design to achieve proof of concept. It includes an adaptive dose decision rule, thus optimizing exposure to the highest and best-tolerated dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06223360, registered on January 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06223360

Protocol for SYNchronising Exercises, Remedies in GaIt and Cognition at Home (SYNERGIC@Home): feasibility of a home-based double-blind randomised controlled trial to improve gait and cognition in individuals at risk for dementia

IntroductionPhysical exercise and cognitive training have the potential to enhance cognitive function and mobility in older adults at risk of Alzheimer's disease and related dementia (ADRD), but little is known about the feasibility of delivering multidomain interventions in home settings of older adults at risk of ADRD. This study aims to assess the feasibility of home-based delivery of exercise and cognitive interventions, and to evaluate the relationship between participants' intervention preferences and their subsequent adherence. Secondary objectives include the effect of the interventions on ADRD risk factors, including frailty, mobility, sleep, diet and psychological health.Methods and analysisThe SYNchronising Exercises, Remedies in GaIt and Cognition at Home (SYNERGIC@Home) feasibility trial is a randomised control trial that follows a 2×2 factorial design, with a 16-week home-based intervention programme (3 sessions per week) of physical exercises and cognitive training. Participants will be randomised in blocks of four to one of the following four arms: (1) combined exercise (aerobic and resistance)+cognitive training (NEUROPEAK); (2) combined exercise+control cognitive training (web searching); (3) control exercise (balance and toning)+cognitive training; and (4) control exercise+control cognitive training. SYNERGIC@Home will be implemented through video conferencing. Baseline and post-intervention assessments at 4-month and 10-month follow-up will include measures of cognition, frailty, mobility, sleep, diet and psychological health. Primary feasibility outcome is adherence to the interventions. Primary analytic outcome is the relationship between pre-allocation preference for a given intervention and subsequent adherence to the allocated intervention. A series of secondary analytic outcomes examining the potential effect of the individual and combined interventions on cognitive, mobility and general well-being will be measured at baseline and follow-up.Ethics and disseminationEthics approval was granted by the relevant research ethics boards. Findings of the study will be presented to stakeholders and published in peer-reviewed journals and at provincial, national and international conferences.Trial registration numberNCT04997681, Pre-results

Asian Cohort for Alzheimer's Disease (ACAD) pilot study on genetic and non‐genetic risk factors for Alzheimer's disease among Asian Americans and Canadians

IntroductionClinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population.MethodsThe ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites. We developed a comprehensive study protocol for outreach and recruitment, an extensive data collection packet, and a centralized data management system, in English, Chinese, Korean, and Vietnamese.ResultsACAD has recruited 606 participants with an additional 900 expressing interest in enrollment since program inception.DiscussionACAD's traction indicates the feasibility of recruiting Asians for clinical research to enhance understanding of AD risk factors. ACAD will recruit > 5000 participants to identify genetic and non-genetic/lifestyle AD risk factors, establish blood biomarker levels for AD diagnosis, and facilitate clinical trial readiness.HighlightsThe Asian Cohort for Alzheimer's Disease (ACAD) promotes awareness of under-investment in clinical research for Asians. We are recruiting Asian Americans and Canadians for novel insights into Alzheimer's disease. We describe culturally appropriate recruitment strategies and data collection protocol. ACAD addresses challenges of recruitment from heterogeneous Asian subcommunities. We aim to implement a successful recruitment program that enrolls across three Asian subcommunities