Clinical Trials & Studies
Observational Studies
NT-ADRC Study (Enrolling)
An observational study to understand the roles and mechanisms of hypertension and other cardiometabolic factors in the earliest phases of Alzheimer's disease and related dementias (AD/ADRD), with the goal of developing innovative biomarkers for early detection and identifying novel therapeutic targets. By integrating clinical, imaging, fluid biomarker, neuropathological, and population-based research approaches, the NT-ADRC aims to generate new insights that will support earlier diagnosis, more precise risk stratification, and the development of effective preventive and therapeutic strategies for AD/ADRD.
CLARiTI Study
The CLARiTI Study is a national longitudinal research initiative designed to identify and validate biomarkers associated with the earliest stages of Alzheimer's disease. Participation in the ADRC / CLARiTI provides NT-ADRC participants access to advanced biomarker assessments, including amyloid and tau positron emission tomography (PET) imaging, and positions the Center within a collaborative network dedicated to accelerating the development of preventive and disease-modifying therapies.
Through CLARiTI, NT-ADRC participants will undergo advanced molecular imaging assessments using the second-generation tau PET tracer MK-6240 and the amyloid PET tracer NAV4694, two of the most sensitive imaging agents currently available for detecting Alzheimer's disease pathology in vivo.
ADNI 4 – The Alzheimer's Disease Neuroimaging Initiative (Enrolling)
ADNI 4 (Alzheimer's Disease Neuroimaging Initiative 4) evaluates people across the United States aged 55-90 in a five-year observational study tracking brain imaging relevant to Alzheimer's disease. This will help to improve clinical trials and initiatives that aim to prevent dementia. In addition to brain magnetic resonance imaging (MRI) measurements, ADNI 4 also incorporates advanced biomarkers like specialized brain PET scans and blood tests. This study builds on the success of previous ADNI studies and seeks to understand Alzheimer's disease brain changes in people representing the entire populace of the United States.
Local PI: Trung Nguyen, M.D.
Ongoing, Enrolling
IPAT - Impact of Intensive Treatment of Systolic Blood Pressure on Brain Perfusion, Amyloid and Tau in Older Adults
The IPAT study is a two-arm open-label randomized controlled trial to assess the effects of intensive pharmacological reduction of high blood pressure (SBP) on brain amyloid and tau protein deposition (Alzheimer's disease pathology) in older adults who are at high risk for AD and related dementias, that is, those who have high blood pressure, family history of dementia, or subjective memory complaints. Participants in this study have state-of-the-art PET imaging, which is able to measure levels of amyloid and tau deposited in the brain.
Local PI: Rong Zhang, Ph.D.
Trial Ready Cohort Down Syndrome (TRC-DS)
As they age, almost 9 out of 10 adults with Down syndrome (DS) will develop Alzheimer's disease. Despite this fact, there have been no clinical trials evaluating treatments to prevent Alzheimer's disease in people with DS. The newly approved anti-amyloid therapies did not include adults with DS in their cohorts, and biological differences related to DS may help to identify specific treatment strategies that would be effective in people with Down syndrome. TRC-DS is part of a larger movement working with people with Down syndrome to advance Alzheimer's disease therapies and potential cures for this population. TRC-DS represents an international effort, coordinated through the Alzheimer's Clinical Trial Consortium (ACTC), through which 16 academic medical centers across the United States seek to develop and test interventions to cure and prevent Alzheimer's disease in people having Down syndrome. TRC-DS is an observational study that enrolls people with Down syndrome between ages 25-55 as a first step toward participating in new clinical trials. TRC-DS is part of the Alzheimer's Clinical Trials Consortium-Down Syndrome (ACTC-DS), a large collaboration of researchers conducting clinical trials for Alzheimer's disease in people with Down syndrome.
Local PI: Brendan Kelley, M.D.
Multi-parametric MR imaging of Alzheimer's disease
Currently, brain MRI is not able to measure or characterize changes in the brain specific to Alzheimer's disease. Although MRI provides detailed information about the structure of the brain, there is a need for advanced techniques that may permit us to track accumulation of proteins related to Alzheimer's disease and may be able to identify people at higher risk for adverse effects of the newly approved treatments that target amyloid protein in the brain. In this study, we investigate a brain imaging protocol that incorporates several advanced MRI techniques that may have greater sensitivity and specificity for AD-related changes than conventional MR methods to detect the presence of accumulated Alzheimer's disease proteins.
Upcoming
RESIST-AD (not yet enrolling)
This study aims to identify new, rare protective mutations that protect the brain from Alzheimer's disease. This approach is fundamentally distinct from the typical paradigm where risk factors are identified and treatments are employed to try to block or reduce them. Here, genetic changes that have already demonstrated safety and efficacy in humans by conferring resistance to AD offer a unique and potentially transformative path to safe, mechanism-driven therapies.
Local PI: Brendan Kelley, M.D. & Laurent Calvier, Ph.D.
Basic Science Studies
Assays for AD and PD
We will develop and test highly sensitive blood-based tests (assays) that are able to detect pathological protein aggregates derived from tau in Alzheimer's disease (AD) patients and α synuclein (α-syn) in Parkinson's disease (PD) patients.
Tau and α-syn accumulation in the brain underlies a number of conditions, including Alzheimer's and Parkinson's disease. In many cases, co-occurrence of tau and α-syn has been observed in AD, indicating that a single therapy against amyloid or tau may not be sufficient to stop or prevent Alzheimer's. Tau and α-syn selectively target vulnerable cell populations within the brain and spinal cord. Multiple lines of evidence suggest that once formed in a vulnerable cell, a tau or α-syn aggregate is able to spread to nearby or connected cells. This is an important mechanism in how Alzheimer's disease spreads throughout the brain once it has started.
The Diamond lab has pioneered development of very selective and sensitive assays (tests) that are capable of detecting the conformation (version) of protein that mediates this spread. These agents have enormous potential as diagnostic tools, because they can potentially be used to detect those protein assemblies in blood – an advance critical to developing and testing new treatment and prevention strategies.
Local PIs: Marc Diamond, M.D., Brendan Kelley, M.D., Vibhash Sharma, M.D.
Ongoing, Not Enrolling
National Institute of Aging Funded Biomarker Study
This study is currently enrolling adults with amnestic mild cognitive impairment to better understand if a concussion might influence the brain circuitry and levels of proteins found within blood to learn about the potential long-term effects of concussion. Participants enrolled into the study will complete a total of 10 visits over a one-to-three-month period, consisting of a blood draw, brief cognitive testing, and multiple sessions of different low-level noninvasive brain stimulation applications.
Local PI: Christian Lobue, M.D.
AHEAD
The newly approved anti-amyloid therapies (lecanemab and donanemab) have demonstrated an ability to impact the biological changes and clinical progression in people having early symptomatic Alzheimer's disease. Advances in biomarkers of Alzheimer's disease have identified accumulation of amyloid plaques in the brain as the earliest detectable signal of Alzheimer's disease. Together, these findings provide a strong rationale to investigate a preventive strategy to address Alzheimer's disease, as embodied by the AHEAD A3-45 Study.
This landmark study tests a secondary prevention strategy. Participants were amyloid positive (as determined by CSF or amyloid PET) and cognitively unimpaired at enrollment. This blinded, randomized, controlled study will determine whether removal of amyloid is feasible, safe, and whether this will prevent or delay symptoms of cognitive decline. It is coordinated through the Alzheimer's Clinical Trial Consortium, an NIA-funded initiative with which UTSW has worked for over a decade.
The trial has been ongoing since 2020 and participants have been having twice-monthly infusions for three-plus years.
Local PI: Brendan Kelley, M.D.
Alzheimer's Plasma Extension Study (APEX)
The Alzheimer's Plasma Extension Study (APEX) is a multicenter, observational study of Alzheimer's disease-related brain changes. In this study, we hope to learn about factors that may preserve memory and thinking in older individuals who do not develop elevated amyloid levels in the brain, which are one of the earliest measurable changes in Alzheimer's disease. Participants in this four-year study are evaluated annually with blood tests, questionnaires, and cognitive testing.
Building on this study, participants in APEX have been invited to also participate in two optional online studies. One investigates how habits and social factors impact future risk of Alzheimer's disease. The second study is exploring the ability of a short online assessment of memory, learning, and thinking skills to identify very subtle cognitive changes that may signal early indications of Alzheimer's disease.
Local PI: Brendan Kelley, M.D.
Preventing Cognitive Decline by Reducing BP Target Trial (PCOT)
Growing evidence suggests that intensive lowering of systolic blood pressure (BP) may prevent mild cognitive impairment (MCI) and dementia. However, current guidelines provide inconsistent recommendations regarding optimal BP targets, citing safety concerns of excessive BP lowering in the diverse population of older adults. The Preventing Cognitive Decline by Reducing BP Target Trial (PCOT) is a pragmatic clinical trial that studies whether lowering BP to less than 130/80 reduces the incidence of cognitive decline. This study employs a collaboratory model that combines clinical decision support applied to home BPs and team-based care delivered in primary care practices, which will have better blood pressure control and a lower incidence of mild cognitive impairment and dementia than patients receiving usual medical care. Will compare the effects of intensive BP control between the intervention and usual care arm on the rate of cognitive decline. We will also investigate the effects of intensive lowering of home BP below 130/80 mmHg with usual care on overall health, including cardiovascular events, death, syncope, falls, fractures, hypotension, and kidney health. This trial is pragmatic, with broad inclusion criteria and delivered in primary care settings by the clinical teams in health systems serving the ethnically and socioeconomically diverse population of North Texas. Lessons from this trial will be valuable to guide clinical practices in BP control and cognitive assessments in real-world settings, as well as design and implementation of future pragmatic trials.
Local PI: Brendan Kelley, M.D.
MARKVCID II
Small vessel diseases (SVD) is common and represents an important age-related brain injury that accounts for substantial vascular contributions to cognitive impairment and dementia (VCID). Although this is known, we do not currently have accurate or valid biological markers that can predict VCID, or that could be used to test strategies to prevent VCID. The purpose of this consortium study is to collect information (biomarkers) that measure the influence of small vessel diseases on cognitive impairment. The biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID) is an NIH-funded study dedicated to identifying and testing promising predictive, diagnostic, and progression biomarkers of the brain small-vessel diseases involved in the vascular contribution to cognitive impairment and dementia (VCID). UT Southwestern is one of the 18 MarkVCID sites located across the United States, all of which work together to deliver high-quality biomarkers ready for use in clinical trials aimed at generating scientific breakthroughs in our understanding and treatment of vascular contributions to cognitive impairment and dementia.
Local PI: Brendan Kelley, M.D.
More details about MARKVCID II
Synaptic Therapy Alzheimer's Research Trial (START)
The Synaptic Therapy Alzheimer's Research Trial (START) is a two-year study that is testing whether an investigational compound (CT-1812) can help to slow memory loss and cognitive decline caused by Alzheimer's disease.
Local PI: Brendan Kelley, M.D.