Clinical Research Directory

A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease

The purpose of this study is to evaluate the efficacy and safety of KarXT + KarX-EC in adult participants with agitation related to Alzheimer's Disease.

Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin

Background: Normal aging, as well as dementias such as Alzheimer s disease, can cause changes in the brain that affect memory, attention, and thinking. Researchers want to know if regular mental tasks (cognitive training) can improve brain function in older adults. They also want to know if psilocybin, a compound found in certain mushrooms, can further support improved brain function. Objective: To learn how regular cognitive training, with or without psilocybin, can improve brain health in older adults. Eligibility: People aged 65 years and older with mild cognitive impairment or early-stage Alzheimer s disease. Healthy older adults with normal cognition are also needed. Design: Participants will be screened. They will have a test of their heart function and an imaging scan. They will have mental health screening and tests of their thinking and memory. They will practice brain-training tasks on a tablet. Participants will be divided into 2 groups: 1 will have cognitive training plus psilocybin; 1 will have cognitive training only. Those having cognitive training only will have 5 or 6 clinic visits. They will take the tablet home to practice brain training daily. They will wear a device to measure brain waves as they sleep; they may have 1 overnight stay in the clinic, or they may wear the device at home. Imaging scans and other tests will be repeated at each visit. Those taking psilocybin will have up to 9 clinic visits. In addition to the visits for cognitive training, they will take 1 psilocybin capsule by mouth 2 weeks apart (the second dose is optional). They will remain in the clinic for 24 hours after each dose.

PET Imaging of Cyclooxygenases in Neurodegenerative Brain Disease

Background: About 5 million adults in the U.S. have Alzheimer s disease or another adult-onset neurodegenerative disorder. Many studies have found that inflammation in the brain contributes to these diseases. Researchers want to find a better way to measure this inflammation. Objective: To learn whether COX-1 and/or COX-2 is elevated in the brains of individuals with neurodegenerative brain disease compared to healthy volunteers. Eligibility: Adults age 18 years and older in good general health who have an adult-onset neurodegenerative dementia, such as AD, FTD, corticobasal syndrome, Huntington s disease, or MCI, ALS and healthy adult volunteers enrolled in protocols 01-M-0254 or 17-M-0181. Design: Participants will be screened with medical history, physical exam with vital signs, and lab tests. They will have a neuropsychological testing. Their heart function will be measured. Participants will have a magnetic resonance imaging (MRI) scan. The MRI scanner is a metal tube surrounded by a strong magnetic field. Participants will lie on a table that slides in and out of the tube. The machine makes noise. Participants will get earplugs. Participants will have 2 PET scans. They will be injected with the study drugs through an intravenous catheter placed in an arm vein. The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of the scanner. A plastic mask will be molded to their head to keep them from moving. A thin plastic tube will be put into an artery at the wrist or elbow crease area. This will be used to draw blood during the scan. Participants will have 2-5 study visits. Participation lasts 1 week to 4 months, depending on scheduling.

Ultra-high-performance Positron Emission Tomography (PET) of Synaptic Density, Reactive Astrogliosis and Tau in Alzheimer's Disease

AIM: to investigate the relationship between synaptic density, tau and reactive astrogliosis in Alzheimer's disease (AD) versus healthy controls and centenarians. DESIGN: this cross-sectional study will recruit patients with biomarker-proven AD, age- and sex-matched healthy controls as well as centenarians. All subjects will undergo a neuropsychological evaluation and ultra-high-performance PET imaging sessions with 18F-SynVesT-1 (synaptic density), 18F-MK6240 (tau) and 18F-SMBT-1 (reactive astrogliosis) as well as structural and diffusion MRI. Blood samples will be taken for the evaluation of blood-based biomarkers.

A Community-Based Screening Program to Identify Participants at High Risk for Amyloid Pathology

The primary purpose of this study is to identify participants with or without symptoms of Alzheimer's Disease (AD) that are at high risk for brain amyloid pathology using blood-based biomarkers.

A Study to Evaluate the Efficacy and Safety of KarXT + KarX-EC for Cognitive Impairment in Alzheimer's Disease

The purpose of this study is to evaluate the efficacy and safety of KarXT + KarX-EC for cognitive impairment in Alzheimer's Disease

The Feasibility, Safety and Tolerability of VR-based Audiovisual Stimulation

This single-session, within-subject, sham-controlled early feasibility study evaluated the safety, tolerability, and feasibility of delivering 40 Hz audiovisual (gamma sensory) stimulation through a virtual reality (VR) headset in cognitively unimpaired older adults and in people with mild cognitive impairment (MCI) due to Alzheimer's disease or mild Alzheimer's disease.

A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SHR 3201 Injection in Healthy Participants

This study is a randomized, double-blind, dose-escalation, placebo-controlled Phase I clinical trial in healthy participants to evaluate the safety, tolerability, and pharmacokinetics of single intravenous and subcutaneous administrations of SHR-3201.

A Study to Investigate the Safety and Effectiveness of SAR448851 in Participants With Early Alzheimer's Disease

This is a randomized, placebo-controlled Phase 2 study to evaluate the efficacy and safety of SAR448851 in early Alzheimer's disease (AD) participants. The purpose of this study is to measure efficacy and safety with once daily oral SAR448851 compared to placebo in participants with mild cognitive impairment due to AD or mild AD dementia and with evidence of cerebral amyloid pathology. This Phase 2 study has 2 parts: Part A is a randomized, double-blind, parallel-group, placebo-controlled study with SAR448851 oral once daily. Part B is an open-label extension. All participants who complete Part A may continue to Part B. An optional dose 2 cohort will be considered to evaluate the efficacy and safety of SAR448851 dose 2 oral once daily. The study duration will be up to 111 weeks for Part A and B, and up to 63 weeks for the dose 2 cohort. The treatment duration will be up to 96 weeks for Part A and B, and up to 48 weeks for the dose 2 cohort. Up to 160 participants will be included in this study.

Choose Myself (Before) Losing Myself

The purpose of this study is to see if an educational interactive booklet about how dementia progresses throughout a person's life can be a helpful tool for patients to think about future decisions that might need to be made regarding their medical care and helping patients discuss their diagnosis and possible future medical decisions with their family or future caregivers.

Use of Wearables for Identifying Factors Associated With Mild Cognitive Impairment and Early-Stage Alzheimer's Disease

Cognitive decline affects millions of older adults worldwide and has a profound impact on individuals, families, and healthcare systems. Mild Cognitive Impairment (MCI) is often an early stage of Alzheimer's disease (AD), a condition for which there is currently no cure. Identifying individuals at risk at the earliest possible stage remains a major challenge. Traditional diagnostic approaches, such as laboratory biomarkers, neuroimaging, and neuropsychological testing, are usually performed at a single point in time and may fail to detect subtle or early changes in brain function and daily behavior. Recent advances in wearable technology, such as smartwatches and smart rings, allow continuous and noninvasive monitoring of physiological and behavioral patterns in daily life. These devices can capture data related to physical activity, sleep, heart rate, and other parameters that may change before clear cognitive symptoms become evident. When combined with clinical, laboratory, neuropsychological, neuroimaging, and electroencephalographic (EEG) information, these data may help identify early signs of cognitive decline. The objective of this study is to develop and validate models capable of detecting early indicators of MCI and early-stage Alzheimer's disease by integrating multiple sources of data, including clinical assessments, blood tests, neuropsychological evaluations, brain imaging, EEG recordings, and continuous data obtained from wearable devices. This is an observational, analytical, single-center, prospective cohort study that will include 150 participants of both sexes, aged 65 years or older. Participants will be recruited from the Dementia Outpatient Clinic of Getúlio Vargas University Hospital (HUGV), through referrals from external neurologists, or via study dissemination on social media. To achieve the target sample size, up to 250 individuals may be approached using a non-probabilistic, convenience-based recruitment strategy. After providing informed consent, participants will undergo a comprehensive medical evaluation, standardized and validated neuropsychological testing, laboratory and imaging examinations, and EEG recording. Participants will also receive training to use wearable devices for continuous monitoring in their daily routines. A control group of older adults without cognitive impairment will be included for comparison. All collected data will be securely stored in a centralized database and used to develop and validate analytical models aimed at identifying patterns associated with cognitive decline. The results of this study may support earlier identification of individuals at risk for MCI and Alzheimer's disease, help guide timely interventions, and potentially delay disease progression and early institutionalization, contributing to improved quality of life for older adults and their families.

A Clinical Trial to Learn About the Effects of VHB937 in People With Early Alzheimer's Disease

This is a multicentre, randomized, double-blind, placebo-controlled, parallel group Phase II study to evaluate the efficacy and safety of VHB937 in participants with early AD followed by an Extension. The double-blind part is 72 weeks long, followed by an extension.

A Retrospective Database Study for the Development and Validation of Algorithms for Intracerebral Hemorrhage and Seizures in Alzheimer's Disease

The primary objective of this study is to develop and validate claims-based algorithms to identify intracerebral hemorrhage \>1 cm in diameter, ensuring differentiation from amyloid-related imaging abnormality-microhemorrhage and hemosiderin deposit (ARIA-H; microhemorrhage, superficial siderosis) in participants with Alzheimer's disease (AD) using claims data in the United States (US) with linkage to electronic health records (EHRs), and to estimate the positive predictive values (PPVs) of the algorithms. The secondary objective of the study is to validate claims-based algorithms to identify new-onset seizures in participants with AD using US claims data with linkage to EHRs and to estimate the PPVs of the algorithms.

Distinguishing Between Alzheimer's Disease, Lewy Body Dementia, and Parkinson's Disease

The study is designed to characterize the clinical, neuropsychological, polysomnographic, and neuroimaging findings among subjects with Alzheimer's disease, Lewy Body dementia, and Parkinsons' Disease.

Glucose Variability and Cognition in Prediabetes

This study examines the association of variability in glucose values over a 10-day period with cognitive function and AD risk markers among individuals with prediabetes, aged 50 or older.

Development of Eye-movement Based Biomarkers in Alzheimer's Disease

This study aims to develop and validate a sensitive and non-invasive eye-tracking software application. This study will obtain participant responses to brief cognitive tests designed to evaluate several key functions known to be affected by Alzheimer's Disease and non-invasive eye movement measurements in response to visually presented stimuli during specifically designed eye-tracking tests. The study data will be used to develop machine learning algorithms and validate a software application intended to track the progressive component of Alzheimer's Disease and associated cognitive changes.

Functionalized Point of Care and 3D Printed Dental Aligners as Devices for Early Detection of Neurodegenerative Diseases

The treatment of dementias of neurodegenerative origin is currently limited to symptomatic drugs that are unable to interfere with the underlying mechanisms of neurodegeneration, as the pathological processes leading to dementia begin decades before the onset of clinical symptoms. In this context, biomarkers for the diagnosis of Alzheimer's disease (AD), the most common form of dementia, are currently available but are either invasive, requiring lumbar puncture, or very expensive, such as PET imaging with amyloid and, potentially, tau tracers. Their widespread application across different clinical settings is therefore impractical. Accordingly, one of the major challenges in this field is the identification of peripheral screening biomarkers with a high negative predictive value (NPV), capable of identifying individuals who are negative for disease-associated biomarkers and can therefore be classified as healthy. Among the most promising biomarkers for neurodegenerative diseases are microRNAs (miRNAs), small non-coding RNA molecules. This study is part of the Italian National Recovery and Resilience Plan (PNRR) project on high-impact Non-Communicable Chronic Diseases (MCnT2), Project Code PNRR-POC-2023-12377354, funded by the Italian Ministry of Health/European Union - Next Generation EU - PNRR M6C2, Investment 2.1, "Enhancement and Strengthening of Biomedical Research within the Italian National Health Service." The participating institutions are Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano and Azienda Ospedaliero-Universitaria "Policlinico San Marco" di Catania. The main working hypotheses of the funded PNRR project are the identification of miRNAs that are dysregulated in patients with AD compared with age-matched healthy individuals and patients with non-AD conditions, and the development of a solution-based sensor for the simplified detection of the identified miRNAs. The sensor will exploit the biochemical methodology developed in Italian Patent No. IT102022000014740 (filed on July 13, 2022), which is capable of measuring the levels of specific enzymes in saliva. The project is structured into three Work Packages (WPs): WP1: Identification and validation of candidate miRNAs and calculation of their negative predictive value (NPV). WP2: Development and optimization of the solution-based sensor and assessment of its ability to detect the findings identified in WP1 using a simpler methodology. WP3: Testing of the sensor in a cohort of patients with AD and controls across different clinical settings, including neurological and dental clinics, in order to assess its applicability in real-world clinical practice. In this study, we aim to: identify the most significantly dysregulated miRNAs in the saliva of patients with AD (WP1); and develop and optimize a solution-based gold nanoparticle biosensor capable of detecting candidate miRNAs in saliva samples from both patients with AD and healthy individuals (WP2).

A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease

This study will evaluate the efficacy and safety of trontinemab in participants with biomarker evidence of Alzheimer's Disease (AD) pathology but with no cognitive or functional impairment, who are at risk for progression to mild cognitive impairment (MCI) due to AD or dementia due to AD.

Transcranial Photobiomodulation (tPBM) in Alzheimer's Disease Study

The purpose of this study is to see if a special light treatment, called photobiomodulation, can help people with memory problems such as Mild Cognitive Impairment or Mild Dementia due to Alzheimer's disease. The light is given to the forehead using an FDA-cleared medical device. This device is cleared to provide topical heating to elevate tissue temperature for temporary relief of muscle and joint pain, muscle spasm and stiffness associated with arthritis. It also increases blood circulation and relaxes muscle tissue. This device is being used "off-label," meaning it will be used in a way that is different than its cleared use. We want to learn whether this light treatment can improve executive function, and whether it changes certain inflammatory and neurodegeneration related signals in the blood. To do this, we will apply the photobiomodulation device to your forehead. We will also ask you questions and give you cognitive tests before and after light treatment. We will also collect blood samples before and after treatment.

Pilot Clinical Trial to Assess the Safety of NMS-01 in Patients With Mild to Moderate Alzheimer's Disease

A single-center, single-arm, prospective, open-label, pilot clinical trial to evaluate the safety and efficacy of the Focused ultrasound stimulator system (NMS-01) for transient Blood-Brain Barrier (BBB) opening in patients with mild to moderate Alzheimer's disease

An Observational Study of LEQEMBI in Routine Clinical Practice in Taiwan

The primary purpose of this study is to describe the incidence and severity of known adverse events, including amyloid-related imaging abnormalities (ARIA)-oedema/effusion (ARIA-E), ARIA-microhemorrhage and haemosiderin deposit (ARIA-H), intracerebral hemorrhage greater than 1 cm, and anaphylaxis (stratified by apolipoprotein E4 variant \[APOE4\] genotype, concomitant antithrombotic therapy, and comorbid cerebral amyloid angiopathy \[CAA\]), in participants treated with LEQEMBI in routine clinical practice in Taiwan. To describe previously unknown adverse events related to long-term safety of LEQEMBI in routine clinical practice, which were not identified in clinical development, as assessed by serious suspected adverse reactions and adverse reactions leading to discontinuation of LEQEMBI treatment. To describe progression to the next stage of Alzheimer's Disease (AD) in routine clinical practice. To describe drug utilization of LEQEMBI and effectiveness of risk minimization measures in routine clinical practice.

A Study to Evaluate ALN-5288 in Patients With Alzheimer's Disease

The purpose of this study is to: * Evaluate the safety and tolerability of intrathecal (IT) ALN-5288 in patients with Alzheimer's Disease (AD) * Evaluate the pharmacodynamic (PD) and pharmacokinetic (PK) effects of ALN-5288 after dose administration

A Study to Evaluate the Efficacy and Safety of KarXT + KarX-EC for Cognitive Impairment in Alzheimer's Disease (MINDSET 2)

The purpose of this study is to evaluate the efficacy and safety of KarXT + KarX-EC for cognitive impairment in Alzheimer's Disease

A Study of Remternetug (LY3372993) in Early Alzheimer's Disease (TRAILRUNNER-ALZ 3)

The purpose of this study is to measure the difference in time to developing or worsening memory, thinking, or functional problems due to Alzheimer's disease occurring in participants receiving study drug compared to placebo. Participation could last up to 255 weeks including screening, a double-blind treatment period, and a double-blind observation period. In addition, eligible participants who receive placebo during the double-blind treatment period may choose to extend their study participation to receive open-label remternetug in an extension period.