Clinical Research Directory

Cholinergic Deep Brain Stimulation for Alzheimer's Disease

This project will investigate the potential of Deep Brain Stimulation to improve cognitive abilities and counteract the effects of Alzheimer's disease. Deep Brain Stimulation electrodes targeting the Nucleus Basalis of Meynert (NB) will be implanted bilaterally in a cohort of patients. NB is the sole source of acetylcholine to the neocortex. Such stimulation may not only treat the cognitive symptoms but may have disease-modifying effects. Drawing from animal experiments in non-human primates that showed success of this approach, intermittent stimulation will be delivered at 60 pulses per second for 20 seconds of each minute for one hour per day. The study team will recruit patients, shortly after first being diagnosed with Alzheimer's disease. The study design will test the safety and efficacy of stimulation, potential benefits in cognitive function assessed with a battery of neurocognitive tests, cholinergic neurotransmission evaluated with Positron Emission Tomography, and ability to reverse Alzheimer's biomarkers, including beta amyloid and tau in the cerebrospinal fluid. Successful completion of this project will lead to a potential new intervention for the cognitive impairments of Alzheimer's disease.

Molecular and Structural Imaging in Alzheimer's Disease: A Longitudinal Study

This is a neuroimaging study designed to learn more about amyloid and tau burden in the brain of patients with typical and atypical Alzheimer's Disease and how burden may change over a one year period.

The Ketogenic Diet for Alzheimer's Disease

The ketogenic diet (KD) is a metabolic shift, which stimulates the liver oxidation of fatty acids to produce ketone bodies. These ketone bodies represent an alternative fuel source for the brain. The benefits of KD in epilepsia have been demonstrated for decades. This diet may also provide benefits in Alzheimer's disease (AD) where neuronal glucose utilization declines from the early stage. Besides, the KD could decrease neuroinflammation, oxidative stress and enhance mitochondrial biogenesis. In murin models of AD, KD or Medium Chain Triglycerides consumption were associated with lower neuroinflammation but also with a diminution of neuropathologic features of AD (amyloid and tau lesions in the brain). Moreover, behavioural effets and improvements in memory and motor function have been highlighted. In humans, recent studies suggest cognitive benefits (memory, executive function) in AD, including in the Mild Cognitive Impairment (MCI) stage. The feasibility and the adherence to the diet proved to be correct, in small samples, in particular in MCI individuals over a short follow-up period (3 to 6 months). This study aims at examining the feasibility of a KD followed-up for one year in participants with early AD (N=70). Change in brain metabolism will be assessed using PET scan after 12 months, comparing KD with control diet. The effects on cognition, quality of life and daily living functioning will be analysed. The safety, nutritional changes and adhesion to the diet will be monitored throughout the study.

Effects of Electrical Stimulation on Verbal Learning in Typical and Atypical Alzheimer's Disease

Alzheimer's disease (AD) is the leading neurodegenerative disease of aging characterized by multiple cognitive impairments. Given the recent failures of disease-modifying drugs, the current focus is on preventing or mitigating synaptic damage that correlates with cognitive decline in AD patients. Transcranial Direct Current Stimulation (tDCS) is a safe, non-invasive, non-painful electrical stimulation of the brain that is shown to act as a primer at the synaptic level when administered along with behavioral therapy, mostly involving language, learning and memory. Previous studies have shown that tDCS over the left angular gyrus (AG) improves language associative learning in the elderly through changes in functional connectivity between the AG and the hippocampus. The investigators' previous clinical trial on the effects of tDCS in neurodegenerative disorders has also shown augmented effects of lexical retrieval for tDCS. In the present study the investigators will compare the effects of active vs. sham tDCS over the AG-an area that is part of the default mode network but also a language area, particularly important for semantic integration and event processing-in two predominant AD variants: probable AD with amnesic phenotype (amnesic/typical AD) and probable AD with non-amnesic (language deficit) phenotype also described as logopenic variant PPA with AD pathology (aphasic/atypical AD). The investigators aim to: (1) determine whether active high-definition tDCS (HD-tDCS) targeting the left AG combined with a Word-List Learning Intervention (WordLLI) will improve verbal learning; (2) identify the changes in functional connectivity between the stimulated area (AG) and other structurally and functionally connected areas using resting-state functional magnetic resonance imaging; (3) identify changes in the inhibitory neurotransmitter GABA at the stimulation site using magnetic resonance spectroscopy. Furthermore, the investigators need to determine the characteristics of the people that may benefit from the new neuromodulatory approaches. For this reason, the investigators will evaluate neural and cognitive functions as well as physiological characteristics such as sleep, and will analyze the moderating effects on verbal learning outcomes. Study results can help provide treatment alternatives as well as a better understanding of the therapeutic and neuromodulatory effects of tDCS in AD, thus improving patients' and caregivers' quality of life.

Senolytic Therapy to Modulate the Progression of Alzheimer's Disease (SToMP-AD) Study

The objective of the study is to determine the safety, feasibility, and efficacy of senolytics in older adults with amnestic mild cognitive impairment (MCI) or early-stage AD (Clinical Dementia Rating (CDR)=0.5 or 1) who are tau PET positive

MIMA Pilot Study: MIcrostructure of the Medial Temporal Lobe in Early Alzheimer's Disease

Patients with Mild Cognitive Impairment (MCI) or Subjective Cognitive Decline (SCD) may or may not develop Alzheimer's disease (AD) dementia. Yet identifying patients at risk is crucial: delaying the onset of the disease by 5 years could reduce prevalence by 50%. To achieve this, we need affordable biomarkers combined with clinically meaningful assessment tools. Current approaches (cognition, imaging or Tau and Amyloid peptide assays) lack precision or specificity (e.g., age-related memory deficits) and involve invasive and costly procedures, sometimes inaccessible in France (e.g., the "AT(N)" framework). Recently, quantitative diffusion MRI (dMRI) has identified in-vivo gray matter microstructural changes linked to hyperphosphorylated Tau protein, which are of great diagnostic value. Still, we ignore whether and how these changes are responsible for early memory impairment in AD. The MIMA-P project will combine multi-compartment models of the high-resolution diffusion signal with a cognitive assessment of memory based on recent models of medial temporal lobe function to assess the relevance of a new affordable, rapid and non-invasive early marker of the disease.

Chronic Treatment of Alzheimer's Disease by Gamma Light and Sound Therapy

Alzheimer's disease (AD) is characterized by significant memory loss, toxic protein deposits amyloid and tau) in the brain, and changes in the gamma frequency band on EEG. The investigator's lab found that boosting gamma waves in AD mouse models using light and sound stimulation at 40Hz not only reduced amyloid and tau in the brain, but also improved memory. The investigators developed a light and sound device for humans that stimulates the brain at 40Hz that can be used safely at home. For the present study, 60 participants with mild Alzheimer's disease will be enrolled and will use this light and sound device at-home daily for 6-months. Investigators will measure changes in brain waves with EEG, blood biomarkers, the microbiome via fecal samples, functional and structural MRI scans, memory and cognitive testing, and questionnaires at 3 in-person visits throughout the study. After the 6-month time point, participants will have the option of continuing in the study for at least one year and completing yearly study visits. This study will provide critical insight into extended therapy involving non-invasive 40Hz sensory stimulation as a possible therapeutic strategy for mild to moderate Alzheimer's disease.

Theta-burst Stimulation on Cognitive Function in the Patients With Young-onset Alzheimer's Disease Dementia

Young-onset dementia (YOD) is a devastating condition, and it produces substantial psychosocial impacts on individual's functioning and family's care burden. Alzheimer's disease (AD) dementia is the most common type in YOD. Medication treatment Response was limited and unsatisfactory. In recent years, repetitive transcranial magnetic stimulation (rTMS) has been considered an alternative for the improvement of cognition in older patients with cognitive impairment. This study aims to examine the effects and potential mechanisms of theta-burst stimulation (TBS) on cognitive function in individuals with young-onset AD.

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL628 in Participants With Early Alzheimer's Disease

This is a Phase 1b, multicenter, randomized, placebo-controlled, double-blind, multiple ascending dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL628 in participants with early Alzheimer's disease (AD), defined as mild cognitive impairment, or mild AD with biomarker evidence of amyloid positivity.

Donepezil Versus Non-drug Treatment in Alzheimer's Disease.

Donepezil, as well as the other symptomatic drugs of Alzheimer's disease, is not any more reimbursed by the French healthcare system, due to a controversy about its efficiency. French health authorities currently preconize a non-rug approach based on cognitive remediation or stimulation. The aim of this study is to compare the efficiency of the 2 approaches (non-drug versus donepezil) on the symptoms of Alzheimer's disease after 6 months of treatment.

A Pivotal Study of Sensory Stimulation in Alzheimer's Disease (Hope Study, CA-0011)

This is a randomized, double-blind, sham-controlled, adaptive-design pivotal study of sensory stimulation in subjects with mild to moderate Alzheimer's disease. Up to approximately 670 subjects will be randomized to 12 months of daily treatment with either Active or Sham Sensory Stimulation Systems. Efficacy will be measured using the Alzheimer's Disease Cooperative Study- Activities of Daily Living (ADCS-ADL) assessment and a combined statistical test (CST) of the ADCS-ADL and the Mini-Mental State Exam (MMSE).

Network-based biOmarker Discovery of Neurodegenerative Diseases Using Multimodal Connectivity

The aim of the NODAL clinical trial is to demonstrate the feasibility of new, low-cost, non-invasive biomarkers of neurodegenerative pathologies as early Alzheimer and Parkinson, based on the estimation of the multimodal connectome.

PMN310 in Patients With Early Alzheimer's Disease (PRECISE-AD)

This Phase 1b study aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of multiple IV infusions of PMN310 in patients with early Alzheimer's disease.

Study of ARO-MAPT-SC in Healthy Subjects and Subjects With Early Alzheimer's Disease

Study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of ARO-MAPT-SC compared to placebo in adult healthy volunteers and in participants with early Alzheimer's disease (AD), defined as mild cognitive impairment due to AD and mild AD dementia.

Lifestyle Interventions for the Treatment of Early Onset Alzheimer's Disease Study

The purpose of this study is to generate preliminary data on the benefit of computerized cognitive training and Tai Chi- Qi Gong training in participants with Early-Onset Alzheimer's Disease. It is hypothesized that participants in the experimental training condition will perform better on outcomes related to cognition, functioning, and mood at follow-up compared to participants assigned to the active control condition.

A Study to Assess THN391 in Subjects With Alzheimer's Disease

This is a Phase 1b study to evaluate different doses of the drug and see whether a drug is safe and how it behaves in the body. THN391 has already been assessed in healthy people without Alzheimer's disease. This is the first study of THN391 in patients with Early Alzheimer's disease. Later studies will evaluate THN391 to see if it is effective for the treatment of Alzheimer's disease. In this study, THN391 will be compared with a placebo (a look-alike substance that contains no drug). The study duration is approximately 6 months in which the participants will visit the clinic approximately 13 times and have 2 telephone calls with the site. Patients who fulfill all criteria to participate in the study, will receive 3 times a monthly dose of THN391 or placebo in the clinic. Assessments that will be done at several timepoints during the study will be blood collection, physical examinations and neurological examinations, 4x an MRI-scan of the head, 2x a spinal tap and some testing of the memory and thinking skills.

Effects of a Widely Used Vaccine Adjuvant in Subjects With Early Alzheimer's Disease Double-blind Study to Assess the Safety and Efficacy of AD04 in Patients With Early Alzheimer's Disease - ADVANCE

The purpose of this randomized, placebo-controlled phase 2b study is to prospectively evaluate AD04's potential as a disease-modifying drug in AD. By evaluating the safety, pharmacodynamics, and efficacy of AD04 in early AD patients, we aim to deliver a comprehensive and robust data set that furthers our understanding of the effects of AD04 in AD pathology.

Study to Evaluate the Efficacy, Safety, and Tolerability of an Anti-MTBR Tau Monoclonal Antibody (BMS-986446) in Participants With Early Alzheimer's Disease

The purpose of this study is to assess the effectiveness, safety, and tolerability of BMS-986446 an Anti-MTBR Tau Monoclonal Antibody in participants with Early Alzheimer's Disease.

Neuropsychological Evaluation in Intellectual Disability (ENDI)

The goal of this observational study is to evaluate the acceptability ofpatients with trisomy 21 (T21) to perform the full battery of ENDI neurospychological tests and each of the subsets. In this study, three types of population will be recruted : normotypic volunteers, patients with Intellectual Disability and patients T21carriers. This study is separated into 2 phases : * A the preliminary phase : this phase will be used to evaluate subtest design, ergonomics and understanding of instructions, and to identify any malfunctions. The observations gathered will enable the principal investigator to refine the digital design of the battery in collaboration with the publishing company. In this phase, normotypical volunteers and patients with intellectual disabilities will be recruted to perform ENDI test battery. * A main phase : this phase will enable to answer to the main objective. in this phase, patients with Trisomy 21 aged between 25 and 65 will be recruted to perform ENDI test battery.

Transcranial Magnetic Stimulation to Slow Down Cognitive Decline in Alzheimer's Disease

New amyloid-targeting drugs for Alzheimer's disease (AD) offer minimal or unclear efficacy and often cause adverse events, highlighting the need for new therapies. In recent years, repetitive transcranial magnetic stimulation (rTMS) has shown increasing success. A recent randomized, double-blind, sham-controlled, phase 2 demonstrated promising results from a 24-week rTMS treatment protocol targeting the precuneus. This brain region is considered a main hub of the human brain connectome and a prominent area of AD pathology. The results showed stable cognitive performance and increased brain activity in the treatment group, whereas the sham group worsened. A replication study is planned to further investigate the working mechanism of precuneus-rTMS in AD and to improve understanding of its therapeutic potential.

A Pivotal Study of LIPUS-Brain in Patients With Early Alzheimer's Disease

This study is a multicenter, randomized, double-blinded, placebo-controlled Phase 3 study comparing LIPUS-Brain transcranial low-intensity pulsed-wave ultrasound device to placebo in patients with Early Alzheimer's Disease. The primary objective of the study is to assess changes in ADAS-J-cog-14 scores from baseline to 72 weeks.

Neuronavigation-guided FUS-induced BBB Opening in Alzheimer's Disease Patients and Its Effects on Brain Amyloid and Tau

The primary purpose of this phase 1b study is to further assess the safety and reversibility of focused ultrasound induced blood-brain barrier opening (FUS-BBBO) in participants with Alzheimer´s Disease (AD) using a single-element transducer with neuronavigation guidance. Preliminary results from our phase 1a study demonstrate that our neuronavigation-guided FUS system was capable of safely and transiently open the BBB in participants with AD. The information collected in this new study may be used to design future clinical trials to ultimately provide a viable alternative for treatment of AD in a safe and noninvasive manner. Our secondary objective includes the assessment of the therapeutic efficacy of FUS-BBBO in reducing amyloid beta and neurofibrillary tangles, the main hallmark pathologies of AD, using PET tracers. Based on our preclinical studies in AD transgenic mouse models, FUS-BBBO alone was able to reduce both the amyloid beta and tau protein load, resulting in improvements in behavioral tasks assessing memory. Therefore, in this new study, the effect of FUS-BBBO on the amyloid beta and tau protein load in patients with AD will be assessed through the use of PET tracers.

Repurposing Nucleoside Reverse Transcriptase Inhibitors for Treatment of AD

This is a randomized, double-blind clinical trial of a daily oral dose of 200 mg emtricitabine vs. placebo in 35 participants with biomarker-confirmed MCI or mild to moderate dementia due to Alzheimer's disease. Study duration for each subject participating in the placebo-controlled research study will be approximately 12 months (up to a 3 months Screening Period, Baseline visit (1 month), 6 months of placebo or emtricitabine dosing, and 1 month follow-up). Participants will have up to 2 months to complete all procedures for the month 6 study visit.

Neuropsychological Profiles and Musical Engagement in Parkinson's and Alzheimer's Disease

The goal of this Multicenter observational pilot study is to Compare the specifics of musical engagement (behaviors related to music in everyday life) in subjects aged over 60 with Alzheimer s disease, Parkinson s disease and control subjects. The main questions it aims to answer are: 1. The description of different profiles of musical engagement in early-stage AD, in PD and in healthy elderly subjects. 2. The extent of executive, mnestic and hedonic dysfunctions will impact differently on emotional engagement, autobiographical evocation and sensitivity to musical reward, and will therefore enable distinct profiles to be drawn up. Participants will have an intervention consisting of an interview with a neuropsychologist lasting approximately 2 hours, including : * A semi-structured interview to check the participants eligibility and gather demographic data. * Neuropsychological tests and questionnaires will then be administered. * A relative of the study participant will help complete questionnaires.