Clinical Research Directory

Slow-SPEED: Slowing Parkinson's Early Through Exercise Dosage

The goal of this clinical trial is two-fold. First to investigate the feasibility of whether a remotely administered smartphone app can increase the volume and intensity of physical activity in daily life in individuals with a LRRK2 G2019S or GBA1 N370S genetic mutation over a long period of time (24 months). Second, to explore the preliminary efficacy of exercise on markers for prodromal Parkinson's disease progression in individuals with a LRRK2 G2019S or GBA1 N370S genetic mutation. Participants will be tasked to achieve an incremental increase of daily steps (volume) and amount of minutes exercised at a certain heart rate (intensity) with respect to their own baseline level. Motivation with regards to physical activity will entirely be communicated through the study specific Slow Speed smartphone app. A joint primary objective consists of two components. First to determine the longitudinal effect of an exercise intervention in LRRK2 G2019S or GBA1 N370S variant carriers on a prodromal load score, comprised of digital biomarkers of prodromal symptoms. The secondary component of the primary outcome is to determine the feasibility of a remote intervention study. The secondary objective is the effect of a physical activity intervention on digital markers of physical fitness. Exploratory outcomes entail retention rate, completeness of remote digital biomarker assessments, digital prodromal motor and non-motor features of PD. Using these biomarkers, the investigators aim to develop a composite score (prodromal load score) to estimate the total prodromal load. An international exercise study with fellow researchers in the United Kingdom are currently in preparation (Slow-SPEED-UK) and active in the Netherlands (Slow-SPEED-NL). Our intention is to analyse overlapping outcomes combined where possible through a meta-analysis plan, to obtain insight on (determinants of) heterogeneity in compliance and possible efficacy across subgroups

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).

Neurofilament Light Chain And Voice Acoustic Analyses In Dementia Diagnosis

This cohort study aims to determine if a blood test can aid with diagnosing dementia in anyone presenting with cognitive complaints to a single healthcare network. The investigators will measure levels of a brain protein, Neurofilament light chain (Nfl), and assess changes in language using speech tests. Participants will have a single blood test and speech test, and will be followed up at 12-months to complete questionnaires and cognitive scales over the phone. The speech test will also be completed again at 12-months. Individuals at risk of a genetic dementia syndrome will be eligible to complete optional genetic testing involving an 'at home' saliva sample.

A Study of Donanemab (LY3002813) in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ 5)

The reason for this study is to assess the safety and efficacy of donanemab in participants with early Alzheimer's disease. The study duration including screening and follow-up is up to 93 weeks.

Effects of Long Term Ventilation Support on the Quality of Life of ALS Patients and Their Families

Amyotrophic lateral sclerosis (ALS) is a serious rapidly progressive disease of the nervous system. The average survival from the time of diagnosis is two to three years. The patient physical and psychological sufferings in ALS are immense, and apart from Riluzole, there is no effective treatment. Care of advanced ALS have an estimated cost of 4-8 million NOK per year. Perhaps the most challenging topic of ALS care is the decision to extend ventilation support into the stages of disease that require treatment both during day and night. In these cases, treatment is clearly life-sustaining and although quality of life may be maintained, the burden of caregiving imposed upon family or health care workers is huge, regardless of tracheostomy (TIV) or non-invasive (NIV) modality. The present study is a longitudinal questionnaire study in Norway measuring overall quality of life, health-related quality of life, and disease-specific quality of life in ALS patients, partners and children before and after the introduction of life sustaining ventilation support. The investigators aim to increase the knowledge on how life-sustaining ventilation support with NIV or TIV affects the quality of life in ALS patients, life partners and children. The results from the study may provide crucial information for clinicians and patients on one of the most difficult ethical issues of ALS treatment. The investigators anticipate that this information will facilitate a shared decision making processes, weighing benefits and disadvantages in a wider perspective.

Neurodegenerative Diseases Registry

With the increase in life expectancy of our population due to advancement of medical diagnosis and treatments, the incidence of age dependent neurodegenerative diseases increased, including Alzheimer's disease (AD), parkinsonian syndromes (PS), small vessel disease (SVD) and motor neuron disease (MND). In spite of the progress of knowing the pathogenesis of various neurodegenerative diseases at molecular and genetic level, they are still very incompletely understood and often cause diagnostic and therapeutic challenges to physicians. Due to the overlapping presentation and similar brain pathology, especially in the early stage of the diseases, it is difficult to differentiate idiopathic Parkinson's disease (iPD) from atypical parkinsonian syndromes, such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Similarly, distinguishing AD from other dementia syndromes including frontotemporal dementia (FTD), dementia with Lewy Bodies (DLB), corticobasal degeneration (CBD) and vascular dementia can be difficult. It is necessary to develop accurate and comprehensive diagnostic tests to properly prognosticate the diseases, start treatments in early stage of the diseases and maximize the accuracy of drug trials for more effective preventive and therapeutic measures for these neurodegenerative diseases. Therefore, the registry aims to generate a large database of cognitive, behavioral, lifestyle and psychological information of the subjects who suffered from neurodegenerative diseases, as well as to examine the genetic basis of neurodegenerative diseases to help decode the pathogenic mechanisms of the diseases. The registry may provide important information to understand symptom development of the neurodegenerative diseases, in which may help physicians to diagnose the diseases more accurately and provide better treatment plans.

Home Exercise for Individuals With Neurodegenerative Disease

The primary goal of this study is to address the need for targeted therapeutic interventions for impairments that impact walking in related neurodegenerative diseases.

Prenatal Education on Environmental Exposures During Pregnancy Study (PEEPS)

The purpose of this project is to reduce maternal environmental exposures to toxicants through a patient education program designed to help pregnant women learn about exposure through consumption of contaminated seafood and to be able to use the lessons they learn to have a better understanding of risk.

Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients

AOC 1001-CS2 (MARINA-OLE) (NCT05479981) is a Phase 2 extension of the AOC 1001-CS1 (MARINA) (NCT05027269) study to evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of multiple-doses of AOC 1001 Administered Intravenously to Adult Myotonic Dystrophy Type 1 (DM1) patients

Observational Pharmaco-Epidemiology Research & Analysis

Greater advances are needed in two separate but related areas in healthcare: 1) the Clinical Decision Support Systems that complement the EHR use in support of routine patient care, population management and disease management; and 2) the use of the point-of-care observational data from the provider-patient encounter that support realworld medical research and healthcare quality measure assessment. Real-world evaluations of treatments of chronic diseases in the context of comorbid conditions and special populations (minorities, women, mentally ill, and those with addiction) are limited. The purpose of the OPERA database is to help address this unmet need in clinical research.

Tau PET/CT in Various Tau-Related Disease Patients

To evaluate the potential usefulness of 18F-S16/T807 positron emission tomography/computed tomography (PET/CT) for the diagnosis of primary and metastatic lesions in various Tau-related disease patients.

Translocator Protein PET/CT in Various TSPO-Related Disease

To evaluate the potential usefulness of 18F-DPA714/FDPA positron emission tomography/computed tomography (PET/CT) for the diagnosis of primary and metastatic lesions in various TSPO-related disease patients.

Beta Amyloid PET/CT in Various Aβ-Related Disease

To evaluate the potential usefulness of 18F-92/AV45, 11C-PIB positron emission tomography/computed tomography (PET/CT) for the diagnosis of primary and metastatic lesions in various Tau-related disease patients.

Neurodegenerative Diseases Progression Markers (MARKERS-NDD)

MARKERS-NDD is a prospective, observational, longitudinal study, which aims to collect data from patients affected by neurodegenerative diseases (NDD) followed longitudinally for routine examinations performed as part of normal clinical practice. Data collected from clinical evaluations, movement analysis, brain imaging, neuropsychological and electroencephalographic assessments, blood chemistry tests will be analysed to carry out statistical investigations and predictive analyses, also using artificial intelligence systems, which allow the identification of new early markers of diagnosis and prognosis of neurodegenerative diseases.

Slow-SPEED-NL: Slowing Parkinson's Early Through Exercise Dosage-Netherlands

The goal of this clinical trial is to investigate the feasibility if a remotely administered smartphone app can increase the volume and intensity of physical activity in daily life in patients with isolated Rapid Eye Movement (REM) sleep behaviour disorder over a long period of time (24 months). Participants will be tasked to achieve an incremental increase of daily steps (volume) and amount of minutes exercised at a certain heart rate (intensity) with respect to their own baseline level. Motivation with regards to physical activity will entirely be communicated through the study specific Slow Speed smartphone app. Primary outcomes will be compliance expressed as longitudinal change in digital measures of physical activity (step count) measured using a Fitbit smartwatch. Exploratory outcomes entail retention rate, completeness of remote digital biomarker assessments, digital prodromal motor and non-motor features of PD, blood biomarkers and brain imaging markers. Using these biomarkers, we aim to develop a composite score (prodromal load score) to estimate the total prodromal load. An international exercise study with fellow researchers in the United States and United Kingdom are currently in preparation (Slow-SPEED). Our intention is to analyse overlapping outcomes combined where possible through a meta-analysis plan, to obtain insight on (determinants of) heterogeneity in compliance and possible efficacy across subgroups

Memory Deterioration in Alzheimer Disease

Semantic AD

Sociodemographic Factors and Criminal Behaviour Preceding Neurodegenerative Disease - Retrospective Register Study

In this retrospective register study, clinically classified individuals with neurodegenerative disease from the years 2010-2021 will be verified from the clinical records from KUH and Oulu University Hospital (OUH). Based on the Finnish social security number, these individuals will be linked to the the national registers of Statistics Finland and Finnish Social and Health Data Permit Authority Findata including incomes, sociodemographic factors, education, occupation, criminal records as well as to the national registers including the bought pharmaceuticals, comorbidities and causes of death. For each study case, 10 randomly selected control cases, matched with age, sex and geographical area, will be used. The aim of the study is to examine: * 1\) The prevalence of criminal and other disruptive behaviour in groups of different neurodegenerative diseases prior to and after the diagnosis * 2\) Changes in employment, residency,income, and marital status prior to and after the neurodegenerative disease diagnosis * 3\) Hospital diagnoses and reimbursable drugs prior to and after the diagnosis * 4\) Causes of death in patients with neurodegenerative disease to study excess mortality of the patients

Characterization of the Serotonin 2A Receptor Selective PET Tracer [18F]MH.MZ in Patients With Neurodegenerative Diseases

It is hypothesize that patients with clinically diagnosed neurodegenerative diseases will have significantly different receptor occupancy of 5HT2A receptors compared to a healthy age/sex-matched control group. This will be tested by measuring 5HT2A receptor density using the PET radioligand (R)-\[18F\]MH.MZ in both populations.

Impact of Harp Therapy on Behavioral Disorders in Nursing Home Residents With Neurodegenerative Disease (ARPE)

The ARPE study looked at whether weekly harp therapy sessions could reduce behavioral problems in older adults living in memory care units of a nursing home (EHPAD). These residents had moderate-to-severe neurodegenerative diseases (such as Alzheimer's disease or related conditions) and displayed disruptive behaviors, especially in the late afternoon and evening. Harp therapy (harpe-thérapie) is a form of receptive music therapy. During each session, a trained harp therapist plays music live for participants. Unlike other music therapy approaches, residents simply listen - they do not need to move, sing, or play an instrument. Receptive music therapy uses sound to promote relaxation, reduce anxiety, and stimulate memory and emotions. The main questions this study aimed to answer were: Can weekly harp therapy sessions reduce neuropsychiatric symptoms (such as agitation, anxiety, and sleep disturbances) in residents with neurodegenerative diseases? Does harp therapy reduce the use of psychotropic medications (sleeping pills, antidepressants, antipsychotics)? Does harp therapy improve residents' well-being immediately before and after each session? Does harp therapy improve the well-being of care staff and help them manage residents' behavioral difficulties? What participants did: Took part in one collective harp therapy session per week in the late afternoon for 12 weeks Were evaluated for behavioral symptoms at the start of the study, at week 6, at week 12, and 3 months after the last session Were assessed for immediate well-being before and after each session Care staff were asked to rate their own well-being twice a week (once after a harp therapy session, once on a day without a session) The study took place at Villa Éléonore, a single nursing home run by LNA Santé in France, and included all eligible residents from two memory care units.

Allopregnanolone Regenerative Therapeutic for Mild Alzheimer's Disease

A phase 2, double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of Allopregnanolone as a regenerative therapeutic for Alzheimer's disease.

A Study of XPro1595 in Patients With Early Alzheimer's Disease With Biomarkers of Inflammation

The goal of this Phase 2 Alzheimer's study is to determine whether 1.0 mg/kg XPro1595 confers a benefit on cognition, function, and biomarkers of white matter and to further evaluate safety and tolerability. The objectives of this study are to determine the safety, tolerability, and efficacy of XPro1595 in patients with early ADi.

Neurologic Stem Cell Treatment Study

This is a human clinical study involving the isolation of autologous bone marrow derived stem cells (BMSC) and transfer to the vascular system and inferior 1/3 of the nasal passages in order to determine if such a treatment will provide improvement in neurologic function for patients with certain neurologic conditions. http://mdstemcells.com/nest/

Establish the First International Database on Semi-quantitative Values Obtained in Scintigraphy With Datscan® in Cadmium-Zinc-Telluride Camera

Datscan scintigraphy is a nuclear medicine examination allowing the diagnosis of neurodegenerative pathologies linked to damage to dopaminergic pathways, such as Parkinson's disease (essential for the differential diagnosis of essential tremor).

A Study of Different Donanemab (LY3002813) Dosing Regimens in Adults With Early Alzheimer's Disease (TRAILBLAZER-ALZ 6)

This study will investigate different donanemab dosing regimens and their effect on the frequency and severity of ARIA-E in adults with early symptomatic Alzheimer's disease (AD) and explore participant characteristics that might predict risk of ARIA. Approximately 375 additional participants will be enrolled in addendum 2. Addendum 3 includes a subset of participants from the main study to receive a single dose. The study will last approximately 91 weeks and include up to 26 visits in the main study.