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297 active trials for Mild Cognitive Impairment

Trial of CORT108297 to Attenuate the Effects of Acute Stress in the Allocortex (CORT-X)

CORT-X will examine if mitigation of stress-mediated pathogenesis of Alzheimer's disease (AD) is a feasible target for intervention in individuals at risk for this disease. This single-site (Baltimore, Maryland) phase II clinical trial is a 2-week, randomized, placebo-controlled crossover study of the effects of the selective glucocorticoid receptor antagonist, CORT108297, on cognitive test performance in 26 individuals with mild cognitive impairment (MCI) due to AD and in 26 cognitively normal individuals with an increased risk for AD due to family history, genetics, and/or subjective memory complaints. All subjects will participate in a brief stressor (public speaking and mental arithmetic) and provide saliva samples so investigators can measure stress hormone response. Then, following 2 weeks of treatment with placebo or CORT108297, in counterbalanced order, participants will complete cognitive tests assessing memory and executive function. All study participants will receive CORT108297 and placebo over the course of this 10-week trial that requires 6 in-person study visits. The primary aims will compare the effects of CORT108297 to placebo on cognitive test performance in individuals with MCI due to AD and in individuals at risk for AD, and describe the side effects of CORT108297 in study participants. Secondary aims will identify subject characteristics that predict positive response to study drug.

Start: June 2021
Virtual Chair Yoga for Older Adults and Caregivers: Randomized Controlled Trial

Over 700,000 Canadians are affected by dementia costing the health care system approximately $10 billion/year. Due to COVID-19, the government has urged individuals over the age of 70 to stay home, putting this population at risk of social isolation. Older adults with mild cognitive impairments (MCIs), dementia, and their caregivers are at an even higher risk of becoming stressed, anxious, and agitated while in lockdown. Unsurprisingly, caregiver burden is extremely common, and often precedes institutionalization of the patient, as the demands of the illness begin to exceed that which the caregiver can sustainably provide. Since social distancing measures have shut down activities and support groups for these individuals, there is an urgent need for scalable, cost-effective, non-pharmacological interventions that can be delivered remotely to improve stress and loneliness. Yoga may be a viable therapeutic modality to address the psychological challenges associated with dementia in patients and caregivers, as it has been shown to decrease stress and improve anxiety and depressive symptoms in various populations. For this reason, the investigators are conducting a randomized controlled trial (RCT) to assess the efficacy of an 8-week virtual chair yoga program to improve stress, psychological symptoms, and caregiver burden. This virtual chair yoga study will engage both older adults with dementia/MCI and caregivers (n=40-60 participants) during COVID-19, which is consistent with the need for decreasing costs and increasing accessibility of novel health interventions during and beyond the pandemic. The investigators will evaluate the effect of this program on stress, loneliness, and mental health related outcomes such as fear of COVID-19, depression, anxiety, and caregiver burden compared to a waitlist control group. There will also be a qualitative component in the form of semi-structured interviews. All quantitative outcomes will be assessed before the program starts and post-intervention and qualitative outcomes will be assessed post-intervention. Participants will be randomly assigned to the treatment group (virtual chair yoga 1 hour per week on Zoom) or the waitlist control group. The investigators hypothesize that after the 8-week yoga program, older adults and caregivers will report lower stress, loneliness, depression, anxiety, fear of COVID-19, and caregiver burden. Results will be available late-2021.

Start: July 2021
CogT BEEM Study (a tDCS Study)

Co-existing neuropsychiatric symptoms (NPS) in patients with mild cognitive impairment (MCI), especially those worsening over time, are associated with more rapid cognitive and functional decline and a greater risk of Alzheimer's disease (AD). Optimal NPS management, meaning effectively managing multiple NPS simultaneously, requires a solid understanding of the shared neural mechanism across NPS. The goal of this proof-of-concept mechanistic intervention study is to validate the causal relationship between a NPS-shared neural circuit the investigators previously discovered and various NPS. The investigators will modify a key region within the NPS-shared neural circuit [i.e. left precentral gyrus (LPG), critical for regulating visual attention] with anodal transcranial direct current stimulation (tDCS). Our central hypothesis is that an activation of LPG and a reorganization of NPS-shared neural circuit will link to improvement in multiple NPS. Using a Stage 0 pilot randomized control trial design the investigators will recruit n = 40 older adults with informant-rated NPS that has worsened in the past 2 years, which is considered the most detrimental type of NPS in MCI. The investigators will assign participants to 4-week active anodal vs. sham LPG online tDCS group. The investigators will assess resting-state and visual attention task-related functional MRI and informant-rated NPS at baseline, and the end of week 4 and week 8, and diffusion MRI at baseline. The two primary aims are to determine the effect of tDCS on NPS-shared neural circuit (Aim 1), as well as the relationship between NPS-shared neural circuit and informant-report NPS (Aim 2). The exploratory aim will be to examine the relationship between NPS and the coherence between structural and functional aspects of the NPS-shared neural circuit. Probing the LPG via anodal tDCS provides a way to experimentally test the causal relationship between our previously discovered NPS-shared neural circuit and informant-rated NPS. The proposed research is highly innovative, while scientifically grounded, for targeting one brain region that may affect multiple NPS. Validating the hypotheses has the potential for future R01 study that directly conducts a Stage 2 trial addressing NPS in MCI, and thus ultimately improves patient's quality of life and reducing caregiving burden.

Start: December 2019
SHARE(D) Stage II: Alzheimer's Risk Disclosure Protocol Piloting

The goal of this study is to test efficacy and safety of person-centered, culturally-informed protocols for disclosure of different combinations of Alzheimer's dementia risk factors. Building on the results from a federally-funded assessment of preferences and needs of racially diverse participants and their respective friends/family members, in regard to Dementia - Alzheimer's Type, we have produced protocols for communication of DAT risk, with attention to specific adaptations in style or content based on individual factors and preferences. These protocols allow for communication of risk based on clinical history and diagnosis, structural neuroimaging, apolipoprotein-E status, and amyloid and tau burden on positron emission tomography. In particular, protocols specify (a) effective methods of communicating risk conferred by each data source, (b) information designed for patients versus informants, (c) psychoeducation needs, and (d) resource/support needs. We will recruit a randomly-selected subset of 10 dyads (including 5 participants who are Non-Hispanic African-American, 5 participants who are Non-Hispanic White) from the Stage I sample to whom we will develop and implement personalized DAT risk disclosure protocols. We will provide preliminary information on the effectiveness of these protocols in terms of patient/co-participant comprehension and recall of feedback provided, satisfaction with the content and format of feedback, and initial changes in mood or behavior immediately following and shortly after risk disclosure sessions.

Start: May 2021
Metformin in Alzheimer's Dementia Prevention

MAP will be a multisite phase II/III 1:1 randomized controlled trial (RCT) of long acting metformin (reduced mass Glucophage XR) vs. matching placebo in 370 men and women with early and late aMCI, without diabetes, not treated with metformin, overweight or obese, aged 55 years to 90 years. The RCT will last 24 months and have 5 visits: baseline, 6-months, 12-months, 18-months, and 24-months. The RCT will be preceded by a screening phase followed by randomization and a titration period in which drug/placebo will be titrated from 500 mg a day (one tablet) to 2,000 mg a day (4 tablets), in increments of 500 mg (one tablet) every 10 days. Participants will remain in the RCT on the tolerated dose, and included in analyses on an intent to treat basis. We expect the attrition rate to be 10%/year. Neuropsychological battery, clinical interviews, physical exam, and phlebotomy will be conducted at baseline and every 6 months. Brain MRI will be conducted in approximately half of the participants (186) twice, at baseline, and after the last study visit at month 24. We will also conduct brain amyloid Positron Emission Tomography (PET) using 18F-Florbetaben, and tau PET using 18F-MK6240 in half of the participants at baseline and end of the RCT. The primary clinical outcome of the study will be changes in the Free and Cued Selective Reminding Test. The secondary clinical outcome will be changes in the Alzheimer's Disease Cooperative Study Preclinical Alzheimer's Cognitive Composite. Secondary subclinical outcomes will be changes in cortical thickness AD signature areas, changes in white matter hyperintensity volume, changes in brain amyloid burden, changes in brain tau burden, and changes in plasma biomarkers of amyloid, tau, and neurodegeneration. The data coordinating center and Imaging Core is located at John Hopkins University. The PET coordinating center is located at UC-Berkeley. The Clinical Coordinating and Monitoring Center and the central laboratory will be located at Columbia. The Research pharmacy function will be shared by the University of Rochester, which will dispense randomization kits, and the University of Iowa, which will receive bulk metformin and identical matching placebo from EMD Serono.

Start: April 2021