Clinical Research Directory

A Trial of Amlenetug (Lu AF82422) in Participants With Multiple System Atrophy (MSA)

The main goal of this trial is to evaluate the efficacy and safety of amlenetug for the treatment of participants with Multiple System Atrophy (MSA).

High-Altitude Neurodegeneration Cohort (HANC) Study

Chronic physiological hypoxia has been implicated in the pathogenesis of multiple system atrophy (MSA), a fatal neurodegenerative disorder of unknown etiology. This prospective, multicenter, observational cohort study (Phase II of the High-Altitude Neurodegeneration Cohort \[HANC\] study) aims to validate the association between chronic hypoxia exposure and incident MSA risk. A total of 20,000 Han Chinese participants aged 40-75 years will be enrolled from 23 sites across China spanning an altitude gradient from 4 m to 4,500 m. All participants will undergo standardized in-person assessment including questionnaires, physical examination, blood collection, and 3-night consecutive nocturnal pulse oximetry monitoring. Participants are to be followed for incident MSA over 12 months. The primary outcome is newly diagnosed MSA (probable or definite per Gilman consensus criteria), adjudicated by an independent panel of movement disorders specialists. Secondary outcomes include the association between altitude strata and MSA incidence, the association between mean nocturnal SpO₂ and MSA incidence, and incidence rates across MSA subtypes (MSA-P and MSA-C).

Clinical Laboratory Evaluation of Chronic Autonomic Failure

Background: The autonomic nervous system controls automatic body functions. Researchers want to improve the tests used to diagnose autonomic failure. Orthostatic hypertension is a drop in blood pressure when a person stands up. Researchers want to focus on this sign of autonomic failure. Objective: To improve testing for conditions that cause autonomic nervous system failure. Eligibility: People ages 18 and older in one of these categories: * Their blood pressure drops when they get up. * They have had a heart transplant or bilateral endoscopic thoracic sympathectomies or have had or will have renal sympathetic ablation Design: All participants will be screened with: * Medical history * Physical exam * Blood and urine tests Some participants will be screened with: * Heart and breathing tests * IV placement into an arm vein * Tilt table testing: Participants lie on a table that tilts while an IV is used to draw their blood. Participants may stay in the hospital for up to 1 week depending on their tests. Tests may include repeats of screening tests and: * Sweat testing: A drug is placed on the skin to cause sweating. Sensors on the skin measure moisture. * Lumbar puncture: A needle is inserted between the bones in the back to collect fluid. * MRI and PET/CT scan: Participants lie on a table that slides into a scanner. For the PET/CT, a small amount of a radioactive chemical will be injected with a small amount of a radioactive chemical. * Bladder catheter placement to collect urine * Skin biopsies: A punch tool removes a small skin sample. * Tests to see how the pupils react to light * Smelling tests * Thinking and memory tests * Questionnaires Participants may have a visit about 2 years later to repeat tests.

Gait Analysis in Neurological Disease

The purpose of this study is to investigate whether speed-dependent measures of gait (so called gait signatures) can be identified in patients with neurological conditions that affect gait, particularly in subjects with parkinsonian disorders.

An Extension Trial to Test if TEV-56286 is Effective in Relieving Multiple System Atrophy

The primary objective of the trial is to describe the long-term safety and tolerability of TEV-56286 administered orally for the treatment of adult participants with Multiple System Atrophy (MSA). A secondary objective of the trial is to further describe the safety and tolerability of TEV-56286. The planned total duration of the trial is approximately 100 weeks.

Use of Accelerometer for Quantification of Neurogenic Orthostatic Hypotension Symptoms

The objective of this study is to find a more objective and accurate way to assess the efficacy of the treatment for neurogenic orthostatic hypotension. For this purpose, the investigators will use an activity monitor to determine the amount of time patients spend in the upright position (standing and walking; upright time) during 1 week of placebo (a pill with no active ingredients) and 1 week of their regular medication for orthostatic hypotension (midodrine or atomoxetine at their usual doses). Total upright time (i.e. tolerance to standing and walking) will be compared between placebo and active treatment to test the hypothesis that it can be used to assess the efficacy of the treatment for orthostatic hypotension and whether this outcome is superior to the assessment of symptoms using validated questionnaires.

Individualized Transcranial Magnetic Stimulation in Parkinsonian Disorders

This clinical trial aims to evaluate whether individualized targeted repetitive transcranial magnetic stimulation (rTMS) can improve motor and non-motor symptoms in patients with parkinsonian disorders. The main question it aims to answer is: * Does individualized targeted rTMS alleviate symptoms of parkinsonian disorders? * Which clinical manifestations of parkinsonian syndromes are responsive to individualized targeted rTMS, and to what degree? Procedures: * Preparation (Screening) Participants will undergo clinical assessments, MRI, and EEG before the treatment. * Treatment (2 Weeks) Participants will receive a 10-day TMS treatment (once daily, Monday-Friday). Each treatment day takes approximately 3-4 hours. Participants need to keep stable medications and rehabilitation routines during this time. * Follow-up (10 Weeks) Participants will undergo follow-up assessments at the end of treatment and 10 weeks after treatment. Assessments include clinical scales, MRI, and EEG.

Trial of Parkinson's And Zoledronic Acid

This home-based study is a randomized (1:1) placebo-controlled trial of a single infusion of zoledronic acid-5 mg (ZA) for the prevention of fractures in men and women aged 60 years and older with Parkinson's disease and parkinsonism with at least 2 years of follow-up. A total of 2650 participants will be enrolled and randomized in the United States. Participants, follow-up outcome assessors, and study investigators will be blinded to assigned study treatment. This trial is funded by the National Institute of Aging.

Research of Biomarkers in Parkinson Disease

The main goal of the GENEPARK consortium is to employ innovative haemogenomic approaches to determine gene expression profiles specific for genetic and idiopathic Parkinson's disease (PD) patients. These gene expression signatures will be utilised clinically as non-invasive diagnostic tests for PD. The sensitivity of the newly developed diagnostic test will be determined by extensive validations on an independent cohort of PD patients, whereas the specificity will be assessed by testing patients with atypical parkinsonisms, including multiple system atrophy, progressive supranuclear palsy and diffuse Lewy body disease. In order to test the specificity of the diagnostic set in other disorders that affect basal ganglia, Huntington's disease and dopa responsive dystonia patients will be analysed. The second objective of the proposal is to determine correlations between gene expression signatures and different stages of PD and thus provide the basis for early diagnosis and monitoring of disease progression. These changes in blood gene expression will be correlated with alterations detected by neuroimaging in the brain of PD patients. Such combinations of molecular and morphological markers of disease may ultimately facilitate the selection and monitoring of neuroprotective therapies for PD. Finally, GENEPARK aims to develop new bioinformatic software tools for selection of genomic biomarkers using microarray data. A set of established computational tools will be applied and novel methods, some of them based on mechanistic modelling of the neurodegenerative diseases, will be developed in order to study the advantages and limitations of the different methodologies. With special emphasis on the careful clinical selection of patients and sufficient power regarding patient numbers, as well as extensive quality control and validation of the data, GENEPARK aims to develop a standardised approach to development and validation of haemogenomic biomarkers of disease.

Biomarkers in Parkinsonian Syndromes

This is a prospective observational study to identify biomarkers in parkinson syndromes. Patients with parkinsonian syndromes at the early stages of disease will be recruited and will be followed up until their established clinical diagnosis or for at least 5 years. In this population, imaging and wet biomarkers as well as clinical data will b systematically collected.

A Trial to Test if TEV-56286 is Effective for Treatment of Participants With Multiple System Atrophy

The primary objective of the study is to evaluate the efficacy of TEV-56286 administered orally for the treatment of adult participants with Multiple System Atrophy (MSA). A secondary objective of the study is to evaluate specific efficacy parameters of TEV-56286. Another secondary objective is to evaluate the safety and tolerability of TEV-56286. The planned study period per participant is 56 weeks including a screening period (up to 4 weeks), a 48-week double-blind treatment period, and a follow-up visit (approximately 4 weeks after the end of the double-blind treatment period). The study duration will be approximately 27 months.

Randomized Double-Blind Placebo-Controlled Adaptive Design Trial Of Intrathecally Administered Autologous Mesenchymal Stem Cells In Multiple System Atrophy

Multiple system atrophy (MSA) is a rare, rapidly progressive, and invariably fatal neurological condition characterized by autonomic failure, parkinsonism, and/or ataxia. There is no available treatment to slow or halt disease progression. The purpose of this study is to assess optimal dosing frequency, effectiveness and safety of adipose-derived autologous mesenchymal stem cells delivered into the spinal fluid of patients with MSA. Funding source: FDA Office of Orphan Product Development (OOPD), Mayo Clinic Executive Dean for Research Transformational Award, Mayo Clinic Regenerative Medicine, and Mayo Clinic Department of Neurology.

Prospective Multicenter Registry Study of Multiple System Atrophy in China

Multiple system atrophy is a rare, rapidly progressive neurodegenerative disease characterized by variable combinations of parkinsonism, cerebellar ataxia, and autonomic dysfunction. Existing natural history studies from North America, Europe, and Japan suggest that clinical phenotypes and disease progression may differ across populations. However, comprehensive multicenter prospective data from Chinese patients with multiple system atrophy remain limited. This prospective multicenter registry study aims to describe the clinical characteristics, longitudinal progression, and outcomes of Chinese patients with multiple system atrophy, to identify factors associated with disease progression and prognosis, and to establish a longitudinal cohort for future biomarker validation and clinical trial design.

Natural History Study of Synucleinopathies

Synucleinopathies are a group of rare diseases associated with worsening neurological deficits and the abnormal accumulation of the protein α-synuclein in the nervous system. Onset is usually in late adulthood at age 50 or older. Usually, synucleinopathies present clinically with slowness of movement, coordination difficulties or mild cognitive impairment. Development of these features indicates that abnormal alpha-synuclein deposits have destroyed key areas of the brain involved in the control of movement or cognition. Patients with synucleinopathies and signs of CNS-deficits are frequently diagnosed with Parkinson disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA). However, accumulation of alpha-synuclein and death of nerve cells can also begin outside the brain in the autonomic nerves. In such cases, syncucleinopathies present first with symptoms of autonomic impairment (unexplained constipation, urinary difficulties, and sexual dysfunction). In rare cases, hypotension on standing (a disorder known as orthostatic hypotension) may be the only clinical finding. This "pre-motor" autonomic stage suggests that the disease process may not yet have spread to the brain. After a variable period of time, but usually within 5-years, most patients with abnormally low blood pressure on standing develop cognitive or motor abnormalities. This stepwise evolution indicates that the disease spreads from the body to the brain. Another indication of this spread is that acting out dreams (i.e., REM sleep behavior disorder, RBD) a problem that occurs when the lower part of the brain is affected, may also be the first noticeable sign of Parkinson disease. The purpose of this study is to document the clinical features and biological markers of patients with synucleinopathies and better understand how these disorders evolve over time. The study will involve following patients diagnosed with a synucleinopathy (PD/DLB and MSA) and those believed to be in the "pre-motor" stage (with isolated autonomic impairment and/or RBD). Through a careful series of follow-up visits to participating Centers, we will focus on finding biological clues that predict which patients will develop motor/cognitive problems and which ones have the resilience to keep the disease at bay preventing spread to the brain. We will also define the natural history of MSA - the most aggressive of the synucleinopathies.

A Phase 2a Study of Foralumab Nasal in Patients With Multiple System Atrophy (MSA)

A Phase 2a Study of Foralumab Nasal in Patients with Multiple System Atrophy (MSA)

Investigation of the Serotoninergic System in Multiple System Atrophy: a Positron Emission Tomography (PET) Study

Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder of the adult associated to a poor prognosis. MSA is clinically characterized by the association of extra-pyramidal, dysautonomic, cerebellar and pyramidal symptoms. Histological and biological studies have raised the hypothesis that, beside the well known dopamine deficiency, some of the symptoms could be related to a dysfunction in serotoninergic neurotransmission. Serotonin is involved in the modulation of several functions impaired in MSA, such as mood, motricity or sleep. The recent description of an association between loss of brainstem serotonin neurons and sudden death in patients with MSA reinforced the hypothesis of a critical role played by this neurotransmitter in the pathophysiology of this disease. Autoreceptors called 5-HT1a are strongly involved in the regulation of serotonin neurotransmission. During the last years several radio-ligands allowing in vivo PET quantification of 5-HT1a receptors, such as 18F-MPPF (4-(2'-methoxyphenyl)-1-\[2'-(N-2''-piridinyl)-p-fluorobenzamide\]methylpiperazine), were developed. Moreover, the investigators recently demonstrated the ability of this brain functional imaging method to investigate, in healthy volunteers, the functional properties of 5-HT1a autoreceptors through an evaluation of their desensitization after a single oral dose of fluoxetine.

Early Molecular Biomarkers for Differentiating Parkinsonian Syndromes

This prospective observational study aims to identify and preliminarily validate molecular biomarkers, including microRNAs and metabolites, for the early differentiation of Parkinson's disease (PD) from atypical parkinsonian syndromes (APS). The study will enroll up to 100 patients with PD, 50 patients with suspected APS, and 50 healthy controls. Participants will undergo clinical assessments and provide blood, urine, and stool samples at baseline and after 12-18 months of follow-up. Molecular analyses, including microRNA profiling, metabolomics, RNA sequencing (RNA-seq), and microbiome analysis, will be performed to identify disease-specific diagnostic signatures. The primary objective is to detect differences in molecular profiles among patients with PD, patients with APS, and healthy controls. Secondary objectives include evaluating the diagnostic accuracy of biomarker panels and assessing longitudinal changes in these biomarkers over time. Although participants will not receive direct therapeutic benefits, the study may contribute to the development of non-invasive tools for the early diagnosis and improved differentiation of parkinsonian disorders.

Assessment of Ambulatory Polygraphy in the Detection of Sleep Apnea in Multiple System Atrophy (SAMSA)

The purpose of this study is to determine whether ambulatory polygraphy during a short hospitalization in a neurology unit has the same performance than inpatient polysomnography, the actual gold standard, in the diagnosis of sleep apnea in patients suffering from multiple system atrophy (MSA).

North American Prodromal Synucleinopathy Consortium Stage 2

This study will enroll participants with idiopathic REM sleep behavior disorder (RBD) and healthy controls for the purpose of preparing for a clinical trial of neuroprotective treatments against synucleinopathies.

Therapeutic Education for Multiple System Atrophy (MSA) Patients and Their Caregivers

Multiple system atrophy (MSA) is a rare neurodegenerative disorder that leads to major disability, forcing patients and caregivers to adapt their environment and lifestyle. Once they receive the diagnosis, patients and caregivers need to understand the symptoms, cope with them, to digest the diagnosis... All these needs are not completely addressed by the current model of care so we created a therapeutic educational program (TEP) program that will last 12 months, involving both patients and caregivers, including a mixed model of in-person visits and continuous on-line activities. Our project aims to target early MSA patients and their caregivers, proposing to test the feasibility (primary objective) of an innovative therapeutic educational program (TEP) for MSA patients.

Evaluation of the Subjective and Objective Painful Threshold in Multiple System Atrophy Pain and Multiple System Atrophy

Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder. MSA is dominated by autonomic/urogenital failure which may be associated with either Parkinsonism (MSA-P subtype) or with cerebellar ataxia (MSA-C subtype). The prognostic of this disease is bad because it ended with the patient's death few years later. No neuroprotective treatment has shown a real efficacy. 50% of patients suffering of MSA frequently experienced painful sensation. The origin of this pain is unknown. In Parkinson disease (PD) ; arguments suggest the implication of dopamine neuromediator pathway in integration and modulation of pain. Several studies suggest the existence of various influences with dopamine implication in the appearance of painful sensation and that would be inhibitory. That's why observed painful symptoms in MSA and PD could be due to a decrease of pain appearance threshold, secondary to a lost of control of sensitizes centres, to Parkinson control. It is interesting to determine if MSA as PD is responsible for a decrease of pain threshold and to characterise the levodopa effect on the patient's pain threshold. Better physiopathology knowledge of pain in MSA is necessary to improve the therapeutic care. Because the efficacy of others treatments is low, it's important to improve the research for a better comfort of patients with a better understanding, analysing and treating of the pain.

Automated Abdominal Binder for Orthostatic Hypotension

The automated inflatable abdominal binder is an investigational device for the treatment of orthostatic hypotension (low blood pressure on standing) in patients with autonomic failure. The purpose of this study is to determine safety and effectiveness of the automated abdominal binder in improving orthostatic tolerance in these patients.

Hemodynamic Mechanisms of Abdominal Compression in the Treatment of Orthostatic Hypotension in Autonomic Failure

Compression garments have been shown to be effective in the treatment of orthostatic hypotension in autonomic failure patients. The purpose of this study is to determine the hemodynamic mechanisms by which abdominal compression (up to 40 mm Hg) improve the standing blood pressure and orthostatic tolerance in these patients, and to compare them with those of the standard of care midodrine. The investigators will test the hypothesis that abdominal compression will blunt the exaggerated fall in stroke volume and the increase in abdominal vascular volume during head up tilt.

Effect of Midodrine vs Abdominal Compression on Cardiovascular Risk Markers in Autonomic Failure Patients

The purpose of this study is to learn more about the effects of abdominal compression and the medication midodrine, two interventions used for the treatment of orthostatic hypotension (low blood pressure on standing), on hemodynamic markers of cardiovascular risk. The study will be conducted at the Vanderbilt University Medical Center and consists of a screening and 2 testing days, one with abdominal compression and one with midodrine. The total length of the study will be about 5 days.