Clinical Research Directory

PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)

Background: About 5 million adults in the United States have age-related brain disorders. These include Alzheimer disease (AD), mild cognitive impairment (MCI), and other dementias. The number of people with these disorders will likely increase as the population ages and life span increases. Inflammation is thought to play a role in AD and MCI. Researchers want to know if an enzyme called PDE4B increases inflammation in people with AD or MCI. Objective: To test whether medical imaging using a new radiotracer (\[18F\]PF-06445974) can measure PDE4B in the brains of people with AD or MCI. Eligibility: People aged 50 years and older with AD or MCI. Healthy volunteers are also needed. Design: Participants will have up to 5 clinic visits with 3 imaging scans of the brain. They will have be screened. They will have a physical exam with blood tests. This will include tests of their heart and nerve function, including memory. Participants will have 2 positron emission tomography (PET) scans. One will use a standard radiotracer. The other will use the study radiotracer. They will receive each tracer through a tube attached to a needle inserted into a vein. During the scan with the study tracer, participants will have a second tube inserted into a vein in the wrist; this tube will be used to draw blood during the scan. Participants will lie on a bed that slides into a doughnut-shaped machine. These visits will take about 6 hours each. Participants will have 1 magnetic resonance imaging (MRI) scan. They will lie on a bed that slides into a cylinder. This visit will take up to 2 hours....

Development, Validation and Normative Data of the Italian Battery for the Recognition of Famous Faces (FAME)

The I-FACE project aims to develop and validate a battery to assess famous-face recognition in people with neurodegenerative diseases and stroke. It will examine face naming, familiarity, and semantic knowledge, establish norms for the Italian population, and test how well the measures identify recognition difficulties in patients with frontotemporal dementia, Alzheimer's disease, and stroke.

An Open Label Dose Escalation Study of VY1706 in Participants With Early Alzheimer's Disease

VY1706 first in human study in early Alzheimer's Disease is a multicenter dose escalation study

MENA/Levant Epidemiological, Registry of Immunological & Clinical Traits (MERIT)

The primary objective of this multicenter observational registry is to characterize the clinical, epidemiological, and biological profiles of individuals of Middle Eastern, North African, and Levantine ancestry, including individuals with chronic medical conditions and healthy volunteers. The registry will collect standardized clinical and participant-reported data, along with biological samples, to support the investigation of disease patterns, health-related characteristics, and population-specific biological and immunological profiles in populations historically underrepresented in biomedical research. The resulting data and samples may support future research into disease-associated biomarkers and underlying biological mechanisms.

CommunityRx-Dementia + Peer Navigation (CRxDpeer)

The CRxDpeer intervention, delivered by a trained peer navigator, in practice called a "peer mentor", includes three evidence-based components: (a) focused education about common social (e.g., food and housing insecurity) and caregiving (e.g., respite and end of life care) needs, (b) activation of personalized community resource information for social and caregiving needs through delivery of a resource list (HealtheRx) at the baseline encounter and coaching on how to communicate with service providers, coordinate services and manage social support (e.g., connect with their peer navigator, reach out to friends or relatives for support, identify support groups, etc.) and (c) ongoing navigation-focused support meant to boost the baseline intervention, including a series of proactive text messages over 12 months. During this time, the subject can respond to and communicate with the peer navigator for ongoing support.

LiO-AD: Lithium Orotate in Alzheimers Disease Feasibility, Biomarker Engagement, and Clinical Response

The goal of this clinical trial is to assess feasibility, safety, tolerability, and central nervous system target engagement of oral lithium orotate in adults with biomarker-confirmed early Alzheimer's disease. The main questions it aims to answer are: * Can participants be recruited, retained, and remain adherent (target ≥80%) over 9 weeks of treatment, and what is the frequency and severity of adverse events? * Does lithium orotate increase cerebrospinal fluid (CSF) lithium concentration from baseline to 9 weeks compared with placebo? Researchers will compare daily lithium orotate to matched placebo to see if lithium orotate demonstrates acceptable feasibility, safety, and tolerability and engages the central nervous system target (CSF lithium). Participants will: * Be randomized in a double-blind manner to receive lithium orotate or placebo for 9 weeks, with titration from week 1: 240 mg/day (10mg elemental lithium) to week 2: 480 mg/day (20mg elemental lithium) and week 3: 720 mg/day (30mg elemental lithium) if tolerated; dose reductions are permitted for side effects. * Attend study visits for safety monitoring, adherence support (caregiver pill logs/diaries), and review of concomitant medications and adverse events. * Provide blood samples and undergo lumbar punctures at baseline and post-treatment to measure CSF and serum lithium and Alzheimer's-related biomarkers; complete brief cognitive testing and neuropsychiatric symptom assessments.

Ultrasonic Debris Clearance to Promote Brain Resilience

This pilot study will evaluate the safety, tolerability, and feasibility of Ultrasonic Debris Clearance (UDC), a noninvasive low-intensity focused ultrasound intervention, in amyloid-positive adults who are asymptomatic but at risk for Alzheimer's disease, or who have mild cognitive impairment or mild dementia. The study is designed to test whether repeated UDC sessions can be delivered safely and feasibly in this population, while also exploring efficacy via biomarkers and clinical measures.

NON-INVASIVE BRAIN STIMULATION FOR MEMORY LOSS IN EARLY ALZHEIMER'S DISEASE

The goal of this clinical trial is to learn if repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, can improve short-term memory in people with early Alzheimer's disease (AD). The study will also evaluate the safety of this approach. The main questions it aims to answer are: * Does rTMS applied to the cerebellum improve short-term memory in people with early AD? * How does this stimulation affect brain activity and connectivity measured by MRI? Researchers will compare active rTMS to sham rTMS (a look-alike procedure that does not deliver brain stimulation) to see if rTMS works to improve memory. Participants will: * Complete a screening visit with medical and memory assessments * Be randomly assigned to receive either active rTMS or sham rTMS (neither participants nor researchers will know the assignment during treatment) * Receive 20 rTMS sessions over 4 weeks (about 20 to 30 minutes per session) * Undergo two MRI scans, one before and one after treatment * Complete memory and thinking tests and questionnaires at baseline, immediately after treatment, and at 3- and 6-month follow-up visits Participation in the study will last about 6 months. The rTMS is generally well tolerated. The most common side effects include mild headache and scalp discomfort during treatment, which are usually short-lasting. MRI is non-invasive and safe for most people. Study procedures will be reviewed to ensure participant safety. Participants may or may not benefit directly from this study. People who receive active rTMS may experience improvement in memory. This research may help improve understanding of memory function in AD and support development of new treatments.

Neuroprotective Effects of Oleanolic Acid and Erythrodiol in Prodromal Alzheimer's Disease

Alzheimer's disease begins many years before memory problems become obvious. People in the early ("prodromal") stage have memory complaints but are still independent in daily life. At present there is no treatment that prevents this stage from progressing to dementia. Olive oil contains two natural compounds, oleanolic acid and erythrodiol. Earlier work by this research team suggests that these compounds may reduce inflammation and oxidative stress and may improve the way the body handles sugars and fats, processes that are also altered in Alzheimer's disease. This study will test whether consuming olive oils that contain these compounds delays the progression from prodromal Alzheimer's disease to dementia. A total of 120 adults aged 50 to 80 years with prodromal Alzheimer's disease will take part at three public hospitals in southern Spain. Participants will be assigned by chance to one of three groups and will consume 55 mL per day of one of three oils for 12 months: olive oil enriched with oleanolic acid, pomace olive oil (which naturally contains both compounds), or a standard commercial olive oil with very low levels of these compounds. Neither the participants nor the staff assessing them will know which oil each person is receiving. Participants will attend study visits at the start of the study and after 6 and 12 months. At these visits they will complete memory and thinking tests, a physical and nutritional assessment, and blood and urine tests.

Precuneus Mapping With Sinaptistim® (an Investigational TMS-EEG System) in Mild to Moderate AD Patients

Transcranial magnetic stimulation (TMS), electroencephalography (EEG), and combined TMS-EEG approaches have been used in human research to characterize cortical excitability and network-level neurophysiologic responses. The SinaptiStim System is an investigational integrated TMS-EEG platform designed to synchronize TMS delivery, EEG acquisition, and is intended to support standardized characterization of neurophysiologic responses and individualized mapping of stimulation parameters relevant to later therapeutic use. The rationale for this early single-site, non-treatment study is to obtain initial clinical evidence that the investigational device can be used safely and as intended in participants with mild to moderate Alzheimer's disease (AD), can acquire EEG data of sufficient quality for the planned application, and can be implemented operationally at the clinical site with appropriate training and usability prior to launch of a larger treatment trial. The study involves two visits, a screening visit with magnetic resonance imaging (MRI) followed by a TMS-EEG mapping visit. Participants who complete this study successfully may be invited to provide informed consent for screening and potential enrollment in a future treatment protocol. This study does not include randomization or a sham control group or therapeutic treatment.

Near-infrared Light Therapy Device for Mild-Moderate Alzheimer's Disease (NirsCure-03A)

This study is a multicenter, randomized, double-blind, sham-device-controlled clinical trial. A total of 320 patients with mild to moderate Alzheimer's disease (AD) are planned to be enrolled. Central stratified block randomization will be applied, with stratification based on disease severity (mild vs. moderate) and Aβ-PET subgroup center status (yes vs. no). Participants will be randomly assigned to either the treatment group or control group in a 1:1 ratio. After enrollment, participants will complete the treatment at home during a 52-week double-blind period. The treatment group will receive therapy using a near-infrared light therapy device, while the control group will use sham device. Both investigators and participants will remain blinded to treatment allocation throughout the double-blind period. Participants who complete the 52-week double-blind treatment period may choose to enter an open-label extension and receive an additional 26 weeks of active near-infrared light therapy.

Adaptation of the Mini-Mental State Examination (MMSE) for the Reunion Island Population

The Mini-Mental State Examination (MMSE) is the most widely used cognitive screening and monitoring test for neurocognitive disorders in current clinical practice. Its French version was published in 1998 by the GRECO group (MMSE-GRECO). However, some items of this French version are not adapted to local Reunionese particularities. The main objective is to propose and validate the psychometric properties of an adapted version of the MMSE, to the Reunionese culture (MMSE-RUN) in a healthy population and in a sick population (Alzheimer's Disease and Vascular Cognitive Disorder), and to compare its performance with the MMSE-GRECO.

[18F]NIDF PET Imaging in Tau-related Diseases

In the field of diagnosing brain neurodegenerative diseases, it is now a well-established practice to inject positron-emitting tracers into the human body. These tracers bind to specific target proteins, allowing their distribution to be visualized via PET imaging. Currently, several research groups worldwide are engaged in developing and clinically validating their own tau imaging agents. This clinical research project aims to visualize abnormal tau pathology in the living human brain using \[18F\]NIDF PET imaging. \[18F\]NIDF is a 2-arene-azaindole-based tracer that offers stronger binding affinity to tau neurofibrillary tangles and reduced non-specific/off-target binding compared to existing tau-PET imaging agents. The study primarily focuses on evaluating the safety and diagnostic efficacy of \[18F\]NIDF PET imaging in human subjects.

Terazosin And Metabolic Engagement in Alzheimer's Disease

The TAME-AD trial will be a randomized, double-blind, placebo-controlled Phase IIa clinical trial to evaluate the metabolic target engagement of terazosin for the treatment of Alzheimer's disease.

Efficacy and Safety of Transcranial Magnetic Stimulation in Treatment of Alzheimer's Disease

This study is grounded in the regulatory mechanisms of the glymphatic system and applies repetitive transcranial magnetic stimulation (rTMS) to the treatment of Alzheimer's disease (AD). The clinical efficacy and safety of rTMS will be systematically evaluated. Furthermore, transcranial magnetic stimulation-evoked potentials (TMS-EEG) and functional near-infrared spectroscopy (fNIRS) will be employed to investigate, from the perspectives of synaptic plasticity and neurovascular coupling, the mechanisms by which rTMS influences glymphatic function. Collectively, this work aims to provide new insights into both the therapeutic effectiveness and the underlying mechanisms of rTMS in AD.

The Role of METhanogens in the PROgression Of Parkinson's Disease and Related Neurological Conditions

Gut problems, such as constipation, can have an important impact on quality of life of people who have them, and have been associated with higher risk of developing neurological diseases such as Parkinson's or Alzheimer's disease. Recent studies suggest that gut problems may also have implications for the progression of these diseases, as constipation is a risk factor for faster Parkinson's and Alzheimer's progression. However, how constipation and brain diseases are linked is unknown. Previous research has suggested that gut changes may lead to inflammation, which could play a role in accelerating the progression of both movement and memory problems in Parkinson's and memory and thinking problems in people with cognitive impairment. Methane is a gas that is naturally produced by microorganisms in the gut. Levels of methane can be measured using a simple breath test. Higher methane levels in the breath are thought to be more common in people with Parkinson's disease (PwP) when compared to people without Parkinson's (healthy controls) and have been associated with gut symptoms, particularly constipation, as well as worse movement problems in PwP, although they are less understood in conditions that affect memory and thinking (like dementia or mild cognitive impairment). The investigators want to better understand the changes in the gut of PwP and people with cognitive impairment (e.g. mild cognitive impairment or dementia). They will compare breath methane levels in PwP, people with cognitive impairment, people with REM Sleep Behaviour Disorder (a sleep condition linked to a higher risk of developing Parkinson's) and healthy participants. Participants will be followed-up over time to assess how methane levels are linked to changes in the blood and the stools, gut function, and clinical symptoms. This study has 2 components: Component 1: observational study, where the study investigators will follow 200 participants over 2 visits, 18 months apart. The study will recruit 4 groups of people: 50 people with Parkinson's disease, 50 people at high risk of developing Parkinson's disease (people with REM Sleep behaviour disorder), 50 people with other conditions affecting cognition (e.g. dementia, mild cognitive impairment), and 50 healthy controls. Component 2: study with 15 people with Parkinson's, who produce high methane levels, to test whether a probiotic (Lactobacillus reuteri) affects how much methane is produced.

Fisetin in Mild Alzheimer's Disease

This pilot study will evaluate the safety and tolerability of the natural health product, fisetin, in older adults with mild cognitive impairment or mild Alzheimer's disease dementia.

Multisensory Environment-Based Occupational Therapy for Alzheimer's Patients

This study aims to examine the effects of a multisensory environment-based occupational therapy intervention on sensory processing, cognitive functions, behavioral and psychological symptoms, and caregiver burden in individuals diagnosed with Alzheimer's disease. Non-pharmacological approaches to Alzheimer's disease management have been shown to slow functional decline, reduce behavioral symptoms, and improve caregivers' well-being. Multisensory environments provide visual, auditory, tactile, proprioceptive, vestibular, olfactory, and gustatory stimuli to support sensory integration and enhance engagement, particularly among individuals with cognitive and communication difficulties. The study will be conducted using a randomized controlled design and will include individuals aged 65 years and older with moderate-stage Alzheimer's disease and their primary caregivers. The intervention will be implemented over eight weeks, with two sessions per week. Outcome measures will include the Adult Sensory Processing Scale, Mini-Mental State Examination, Loewenstein Occupational Therapy Cognitive Assessment-Geriatric, Neuropsychiatric Inventory, and Caregiver Burden Inventory. The study is expected to contribute to the evidence base supporting sensory-based occupational therapy interventions in dementia care.

Validation of a Remediation Method for Memory Impairments Through Motor Encoding in Patients With Alzheimer's Disease

In France, over 1.5 million people suffer from mild cognitive impairment, often a precursor to Alzheimer's disease (AD), whose global prevalence could reach 153 million by 2050. With no curative treatment available, maintaining patients' autonomy at home is essential to mitigate the negative effects of institutionalization and reduce economic costs. Non-pharmacological approaches, such as cognitive training, have shown potential in stabilizing cognitive functions. Research suggests that motor networks and procedural memory remain relatively preserved in early AD, and bodily engagement during encoding enhances memory. For patients with motor impairments, motor imagery (MI) activates these networks without actual movement. Additionally, dynamic visual cues, like videos, reduce cognitive load compared to static images. This project aims to combine real action, MI, and dynamic visual supports to optimize memory. By validating 120 videos of daily activities, it will assess the impact of action on recall, evaluate MI's effectiveness for patients with mobility limitations, and confirm the superiority of videos over static images. The results could support the development of digital tools, such as serious games, to enhance patients' autonomy and address aging-related challenges.

Efficacy of Lymphatic-Venous Anastomosis Plus Donepezil Versus Donepezil Alone for Alzheimer's Disease

This study employed a multicenter, randomized controlled trial (RCT) design to evaluate the efficacy and safety of deep cervical lymphatic/lymph node-venous anastomosis combined with oral donepezil compared to donepezil monotherapy in patients with Alzheimer's disease and moderate dementia. Participants were randomized using a central randomization system with stratified block design, with the study center and age group (50-64 years, 65-80 years) as stratification factors. While study participants and surgical investigators could not be blinded due to the nature of the intervention, efficacy assessors and imaging specialists remained blinded to ensure the objectivity and reliability of the findings. The intervention group received deep cervical lymphatic/lymph node-venous anastomosis (detailed surgical procedure is specified in the protocol) in combination with oral donepezil (5-10 mg/day), while the control group received oral donepezil alone. The total treatment and follow-up period was 18 months, with assessments conducted at baseline, 1 week, 1, 3, 6, 12, and 18 months post-operation. These included neuropsychological evaluations (MMSE, MoCA, CDR, BADL, IADL, NPI, AES), neuroimaging (MRI, PET, ultrasound), fluid biomarker analyses (CSF and blood levels of Aβ, Tau, neuroinflammatory factors, etc.), and safety monitoring. The primary efficacy endpoint was the change in CDR-SB score at 12 months post-treatment. Secondary endpoints included changes in multiple cognitive scales, neuroimaging metrics, and biomarkers at 18 months. Safety indicators encompassed adverse event recording, vital signs, and laboratory tests.

Development of a Home Test for Measuring Blood P-tau217 in Alzheimer's Disease Using the Tasso Lancet Device

This study compares p-tau217 concentrations in blood collected via the Tasso device versus standard venipuncture in subjects with and without Alzheimer's disease, including a subset with confirmed amyloid pathology.

Low-Dose Radiotherapy for Alzheimer's Disease

To evaluate the safety and tolerability of low-dose whole brain radiotherapy (WBRT) delivered as an induction course of 0.3 Gy × 10 fractions (3.0 Gy total) followed by 12 months of monthly maintenance LDRT (0.3 Gy × 10 fractions; 3.0 Gy total) in patients with Alzheimer's disease or dementia with inflammatory components

SAD Study of CGB3002 in Healthy Participants

This is a randomized, double-blind, placebo-controlled phase I clinical study to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of single ascending IV doses of CGB3002 in healthy participants. CGB3002 is being developed to treat Alzheimer's Disease.

Brain Wave Informed Non-invasive Brain Stimulation: Improving Neural Networks of Working Memory in Dementia: a Proof-of-concept Study

Working memory helps us hold information for a short time so one can think and make decisions. It keeps thoughts on track. As one gets older, working memory gets weaker. In people with dementia, it gets much worse, making it harder to talk with others, follow directions, or remember things like shopping lists. This may happen because brain waves that support working memory fall out of sync. Researchers can see these brain waves using a test called EEG. In this study, the investigators will try to get these brain waves back in sync using a safe, non-invasive form of brain stimulation called transcranial magnetic stimulation (TMS), and will time it to each person's brain waves to make it more effective. The goal is to improve working memory in people with dementia. If successful, dementia patients may be able to be more independent taking pressure off their families.