Alzheimer's Disease clinical trials at UCSF

The reason for this study is to see how safe and effective the study drug donanemab is in participants with early Alzheimer's disease. Additional participants will be enrolled to an addendum safety cohort. The participants will be administered open-label donanemab.

This study will be conducted to evaluate the efficacy of lecanemab in participants with early Alzheimer's disease (EAD) by determining the superiority of lecanemab compared with placebo on the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months of treatment in the Core Study. This study will also evaluate the long-term safety and tolerability of lecanemab in participants with EAD in the Extension Phase and whether the long-term effects of lecanemab as measured by the CDR-SB at the end of the Core Study is maintained over time in the Extension Phase.

In this study, researchers will learn more about a study drug called BIIB080. The study will focus on participants with mild cognitive impairment or mild dementia due to AD. The main question researchers are trying to answer is if BIIB080 can slow the worsening of AD more than placebo. It will focus on what dose of BIIB080 slows worsening of AD the most. To help answer this question, researchers will use the Clinical Dementia Rating-Sum of Boxes, also known as the CDR-SB. - Clinicians use the CDR-SB to measure several categories of dementia symptoms. - The results for each category are added together for a total score. Lower scores are better. Researchers will also learn more about the safety of BIIB080. The study will be split into 2 parts. The 1st part is the Placebo-Controlled Period. The 2nd part is the Long-Term Extension (LTE) Period. The 2nd part of the study will help researchers learn about the long-term safety of BIIB080, and how it affects the participant's daily life, thinking, and memory abilities in the longer term. A description of how the study will be done is given below. - After screening, participants will first receive either a low dose or high dose of BIIB080, or a placebo, as an injection into the fluid around the spinal cord (cerebrospinal fluid). A placebo looks like the study drug but contains no real medicine. - Participants will receive BIIB080 or placebo once every 12 weeks or 24 weeks. - After 76 weeks of treatment in the Placebo-Controlled Period, eligible participants will move onto the Extension Treatment period, which will last 96 weeks. - In the extension period, participants who received placebo will be switched to high dose BIIB080 every 12 or 24 weeks. - Participants may be in the study for up to 201 weeks, or about 4 years. This includes the screening and follow-up periods. - Participants can continue to take certain medications for AD. Participants must be on the same dose of medication for at least 8 weeks before the screening period. - After the screening period, most participants will visit the clinic every 6 weeks.

The primary purpose of this study is to determine whether treatment with lecanemab is superior to placebo on change from baseline of the Preclinical Alzheimer Cognitive Composite 5 (PACC5) at 216 weeks of treatment (A45 Trial) and to determine whether treatment with lecanemab is superior to placebo in reducing brain amyloid accumulation as measured by amyloid positron emission tomography (PET) at 216 weeks of treatment (A3 Trial). This study will also evaluate the long-term safety and tolerability of lecanemab in participants enrolled in the Extension Phase.

The goal of the Alzheimer's Tau Platform (ATP) is to evaluate the safety and effectiveness of tau-directed therapies, alone or in combination with donanemab, in adults aged 50-80 with late preclinical or early prodromal Alzheimer's disease. This platform trial allows for the simultaneous testing of multiple tau therapies under a shared master protocol. This means that multiple investigational products will be tested simultaneously or sequentially. Each investigational product will be tested in a regimen. The main questions the platform trial aims to answer are: - Does any tau-directed therapy, alone or in combination with donanemab, reduce brain tau deposition more than donanemab alone? - Does any tau-directed therapy, alone or in combination with donanemab, slow disease progression based on fluid biomarkers, imaging, or clinical measures? Participants will: - Be randomized to a treatment regimens, each containing different tau therapies. The exact number of treatment regimens that will active at the time of screening will change over time. - Receive donanemab or placebo for 6 months, followed by 24 months of tau therapy alone or in combination with donanemab - Undergo regular cognitive testing, brain scans (MRI/PET), and biomarker assessments over 30 months Participants will have an equal chance to be randomized to all regimens that are active at the time of screening. Once randomized to a regimen, participants will be randomized to one of three arms: (1) tau therapy alone, (2) a combination of donanemab and tau therapy, or (3) donanemab alone. New regimens will be continuously added as new investigational products become available. The Alzheimer's Tau Platform Trial will enroll additional participants as each new regimen becomes available. ATP is expected to launch with two regimens: - Regimen A: Tau1 - Regimen B: Tau2

The Care Ecosystem is an accessible, remotely delivered team-based dementia care model, designed to add value for patients, providers and payers in complex organizational and reimbursement structures. Care is delivered via the phone and web by unlicensed Care Team Navigators, who are trained and supervised by a team of dementia specialists with nursing, social work, and pharmacy expertise. The evidence base to date suggests that the Care Ecosystem improves outcomes important to people with dementia, caregivers, and payers when delivered in a controlled research environment, including reduced emergency department visits, higher quality of life for patients, lower caregiver depression, and reduced potentially inappropriate medication use (Possin et al., 2019; Liu et al., 2022). The investigators propose a rapid pragmatic trial in 6 health systems currently offering the Care Ecosystem program in geographically and culturally diverse populations. The investigators will leverage technology, delivering care via the phone and web and using electronic health records to monitor quality improvements and evaluate outcomes while maximizing external validity. The investigators will evaluate the effectiveness of the Care Ecosystem on outcomes important to patients, caregivers, healthcare providers, and health systems during the pandemic. By evaluating the real-world effectiveness in diverse health systems that are already providing this model of care, this project will bridge the science-practice gap in dementia care during an unprecedented time of heightened strain on family caregivers, healthcare providers and health systems.

The purpose of this study is to better understand the experience of living alone in older age with cognitive impairment. We recruit adults 55+ living alone with cognitive impairment such as Alzheimer's disease or mild cognitive impairment. This study investigates the priorities and concerns of older adults living alone with cognitive impairment. Participants are interviewed 5 times for one hour in their homes within 3 months at a time that works for them.

There is a major unmet need for timely, non-invasive, and low-burden evaluation of patients presenting with mild cognitive impairment (MCI) and dementia. MCI impacts 12-18% of people in the United States over age 60 years (Alzheimer's Association. Mild Cognitive Impairment (MCI) available at https://www.alz.org/alzheimers-dementia/what-is-dementia/related_conditions/mild-cognitiv e-impairment. Accessed August 16, 2022). MCI does not substantially interfere with daily activities, although complex functional tasks may be performed less efficiently (Knopman DS, Petersen RC. Mild cognitive impairment and mild dementia: a clinical perspective. Mayo Clin Proc. 2014;89(10):1452-1459. doi:10.1016/j.mayocp.2014.06.019). Approximately 30% of MCI patients have Alzheimer's disease (AD) as a cause of their symptoms (Lopez,OL, Kuller LH, Becker JT, et al. Incidence of dementia in mild cognitive impairment in the cardiovascular health study cognition study. Arch Neurol. 2007;64(3):416-420.doi:10.1001/archneur.64.3.416)). In contrast, dementia is defined by chronic, acquired loss of two or more cognitive abilities caused by brain disease or injury, often associated with significant interference with the ability to function at work or at usual activities. (Knopman DS, Petersen RC. Mild cognitive impairment and mild dementia: a clinical perspective. Mayo Clin Proc. 2014;89(10):1452-1459. doi:10.1016/j.mayocp.2014.06.019). Approximately 60-80% of dementia patients have AD as a cause of their symptoms (Alzheimer's Association. Mild Cognitive Impairment (MCI) available at https://www.alz.org/alzheimers-dementia/what-is-dementia/related_conditions/mild-cognitiv e-impairment. Accessed August 16, 2022).