Clinical Research Directory

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.

Study of [11C]CPPC as a Clinical PET Radioligand Biomarker of Microglial Activation in ALS

1. Establish the safety and tolerability of the 5-cyano-N-(4-(4-\[11C\]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide (\[11C\]CPPC) PET radioligand in ALS patients and controls 2. Examine whether \[11C\]CPPC PET uptake is elevated in brains of ALS patients and whether there is a correlation with clinical phenotype. 3. Correlate \[11C\]CPPC PET imaging with other ALS outcome measures and biofluid biomarkers 4. Examine longitudinal changes in \[11C\]CPPC PET imaging during disease course.

Efficacy and Safety Extension Study of Oral Edaravone Administered in Subjects With ALS

To evaluate and compare the efficacy of two dosing regimens of oral edaravone in subjects with amyotrophic lateral sclerosis (ALS), based on the time from the randomization date in Study MT-1186-A02 to at least a 12-point decrease in Revised ALS Functional Rating Score (ALSFRS-R) or death, whichever happens first, over the course of the study or until oral edaravone is commercially available in that country

Using the EHR to Advance Genomic Medicine Across a Diverse Health System

Given the expansion of indications for genetic testing and our understanding of conditions for which the results change medical management, it is imperative to consider novel ways to deliver care beyond the traditional genetic counseling visit, which are both amenable to large-scale implementation and sustainable. The investigators propose an entirely new approach for the implementation of genomic medicine, supported by the leadership of Penn Medicine, investigating the use of non-geneticist clinician and patient nudges in the delivery of genomic medicine through a pragmatic randomized clinical trial, addressing NHGRI priorities. Our application is highly conceptually and technically innovative, building upon expertise and infrastructure already in place. Innovative qualities of our proposal include: 1) Cutting edge EHR infrastructure already built to support genomic medicine (e.g., partnering with multiple commercial genetic testing laboratories for direct test ordering and results reporting in the EHR); 2) Automated EHR-based direct ordering or referring by specialist clinicians (i.e., use of replicable modules that enable specialist clinicians to order genetic testing through Epic Smartsets, including all needed components, such as populated gene lists, smartphrases, genetic testing, informational websites and acknowledgement e-forms for patient signature); 3) EHR algorithms for accurate patient identification (i.e., electronic phenotype algorithms to identify eligible patients, none of which currently have phenotype algorithms present in PheKB; 4) Behavioral economics-informed implementation science methods: This trial will be the first to evaluate implementation strategies informed by behavioral economics, directed at clinicians and/or patients, for increasing the use of genetic testing; further it will be the first study in this area to test two forms of defaults as a potential local adaptation to facilitate implementation (ordering vs. referring); and 5) Dissemination: In addition to standard dissemination modalities,PheKB95, GitHub and Epic Community Library, the investigators propose to disseminate via AnVIL (NHGRI's Genomic Data Science Analysis, Visualization, and Informatics Lab-Space). Our results will represent an entirely new paradigm for the provision of genomic medicine for patients in whom the results of genetic testing change medical management.

Initiation of Noninvasive Ventilation in ALS Patients With Chronic Respiratory Insufficiency

This research will study whether noninvasive ventilation (NIV) used to treat chronic respiratory insufficiency in patients with amyotrophic lateral sclerosis (ALS) can be initiated as successfully in the outpatient setting as in the conventional inpatient setting, and what the costs of these alternative initiation methods are.

Digital Speech Markers for Monitoring ALS in Spanish Speakers

The goal of this observational study is to learn how speech and breathing change over time in Spanish-speaking individuals with amyotrophic lateral sclerosis (ALS) compared to age- and gender-matched individuals without ALS. The main questions it aims to answer are: Can speech and breathing measures collected through a smartphone application serve as reliable digital biomarkers to track bulbar disease decline in Spanish-speaking people with ALS? How do these measures differ between individuals with ALS and those without ALS? Researchers will compare Spanish-speaking participants with ALS to age- and gender-matched healthy controls to see if specific speech and breathing features can identify or predict bulbar decline. Participants will: Use a Spanish-language smartphone application to record speech and breathing tasks over time. Complete assessments of speech, breathing, and functional abilities (e.g., ALS Functional Rating Scale). Provide data that will be compared to caregiver reports and clinical outcomes to validate new digital biomarkers.

Multicenter ALS Imaging Study

This is a multi-site study of ALS participants and healthy controls who will undergo brain and cervical spine MRIs and NfL blood testing at up-to 4 time points over the course of a year. The primary goal is to identify objective biomarkers of disease progression that are biologically relevant, linearly progressive, and sensitive to change.

Healey ALS MyMatch Common Screening Protocol

The goal of the Healey ALS MyMatch Common Screening Protocol (MCSP), an observational study, is to identify individuals with ALS who may be eligible to be matched to a currently enrolling ALS MyMatch trial. Participants will complete a MCSP Screening Visit and undergo clinical assessments, laboratory testing, and biomarker analyses to determine preliminary trial eligibility. The study also characterizes clinical, genetic, and biofluid biomarker profiles, assesses the prevalence of ALS-associated gene variants, and banks blood samples for future ALS and biomarker research. MCSP enables simultaneous screening for multiple trial-specific biomarkers and uses a targeted medical history form to optimize matching of participants to appropriate MyMatch trials.

Safety Study of Oral Edaravone Administered in Subjects With ALS

The objective of this study is to evaluate the long-term safety and tolerability of oral edaravone in subjects with Amyotrophic Lateral Sclerosis (ALS) over 24 and 48 weeks.

Extension Study Following the Studies MT-1186-A03 or A04 to Evaluate the Safety of Oral Edaravone in Subjects With ALS

The purpose of this study is to evaluate the safety of oral edaravone at a dose of 105 mg administered once daily for 10 days out of a 14-day period, followed by a 14-day drug-free period. This study will be continued until the earlier date when oral edaravone is commercially available at each site in Japan or August 2023.

Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS

To evaluate and compare the efficacy of two dosing regimens of oral edaravone in subjects with amyotrophic lateral sclerosis (ALS) based on the change in ALS Functional Rating Scale- Revised (ALSFRS-R) score from baseline up to Week 48:

A Study of TCD601 (Siplizumab) in Newly Diagnosed Adult Amyotrophic Lateral Sclerosis (ALS) Patients

The purpose of this study is to investigate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of TCD601 (siplizumab) in newly diagnosed adult ALS patients.

Intravenous Immunoglobulin (IVIG) and Blood-Brain Barrier Disruption in Amyotrophic Lateral Sclerosis (ALS)

The goal of this study is to evaluate the safety and feasibility of IVIg administration in conjunction with primary motor cortex BBB opening using the Next Generation Dome Helmet (NGDH) FUS in adult participants with ALS.

The BANYAN Trial, an ALS MyMatch Trial Evaluating Safety, Biomarker Activity, and Microglial Activation of Nasal Foralumab

The goal of this clinical trial is to learn whether a nasal spray medicine called foralumab is safe and easy to tolerate in adults with amyotrophic lateral sclerosis (ALS). ALS is a disease that slowly damages the nerve cells that control movement, causing muscles to grow weaker over time. Foralumab is being studied as a possible way to calm the inflammation and immune system activity that are thought to play a role in ALS. The main questions it aims to answer are: 1. Is nasal foralumab safe for people with ALS, and how well do they tolerate it over 12 and 24 weeks of treatment? 2. Does foralumab change certain markers in the blood and spinal fluid, and lower inflammation in the brain, compared with a placebo? Researchers will compare people who take foralumab to people who take a placebo (a matching nasal spray with no medicine in it) to see how the two groups differ in safety and in these markers. About 44 adults aged 18 to 75 with ALS will take part. For the first 12 weeks, participants will be randomly assigned so that about 3 in 4 use foralumab and about 1 in 4 use the placebo. Neither the participants nor the study staff will know who is using which during this time (this is called "double-blind"). After the first 12 weeks, everyone who continues will use foralumab for the next 12 weeks. Participants will: * Spray the study treatment into both nostrils 3 times a week, on alternate days, in cycles of 2 weeks on treatment followed by 1 week off * Learn to use the nasal spray device so they or a caregiver can give most doses at home * Take part for about 8.5 months in total, which includes screening, 24 weeks of treatment, and a safety check-in about 4 weeks after the last dose * Attend some visits at the study clinic and complete others remotely by phone or video * Have study tests that may include blood samples, breathing and muscle-strength checks, and - for those who agree and at certain study centers - spinal fluid samples and brain scans to measure inflammation

Digital Tools for Assessment of Motor Functions and Falls in ALS

This is a 48-week single arm study that incorporates digital tools for assessing motor function as part of an ALS telemonitoring program. During the study, neck- and wrist-worn "activity sensors" (PAMSys, BioSensics, Newton, MA) that will be worn by subjects while performing tasks of daily living. Subjects will also complete a motor, speech, and handwriting assessment during site visits. Subjects will complete a digital home assessments of speech, handwriting, and pattern tracing tasks throughout the study, and report any falls which occur on the study tablet. The investigators will explore whether functional changes are sensitive to self-reported changes on the ALS Functional Rating Scale - Revised (ALFRS-R) over the length of the study.

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/

Feasibility of the BrainGate2 Neural Interface System in Persons With Tetraplegia (BG-Tablet-01)

People with brainstem stroke, advanced amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease), or other disorders can become unable to move or speak despite being awake and alert. In this project, the investigators seek to further translate knowledge about interpreting brain signals related to movement, and to further develop an intracortical brain-computer interface (iBCI) that could restore rapid and intuitive use of communication apps on tablet computers by people with paralysis.

ALS/MND Natural History Study Data Repository

This is a data repository for multi-site multi-protocol clinic-based Natural History Study of ALS and Other Motor Neuron Disorders (MND). All people living with ALS or other MNDs who attend clinics at the Study hospitals (sites) are offered to participate in the Study. The Sites collect so-called Baseline information including demographics, disease history and diagnosis, family history, etc. At each visit, the Sites also collect multiple disease-specific outcome measures and events. The information is captured in NeuroBANK, a patient-centric clinical research platform. The Sites have an option to choose to collect data into 20+ additional forms capturing biomarkers and outcome measures. Captured data after its curation are anonymized (all personal identifiers and dates are being removed), and the anonymized dataset is shared with medical researchers via a non-exclusive revocable license. Funding Source - Biogen, Inc.; Mitsubishi Tanabe Pharma America; FDA OOPD.

INdependence Through Endovascular Neuroprosthetic Technology (INTENT): an Early Feasibility Study

INdependence Through Endovascular Neuroprosthetic Technology (INTENT): an Early Feasibility Study

ECoG BMI for Motor and Speech Control

Test the feasibility of using electrocorticography (ECoG) signals to control complex devices for motor and speech control in adults severely affected by neurological disorders.

Functional Outcomes and Control Using Synchron BCI - Canada

Functional Outcomes and Control Using Synchron BCI - Canada (FOCUS-CAN)

AMX0114 in Adult Participants With Amyotrophic Lateral Sclerosis

This study is a placebo-controlled Phase I study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide (ASO) AMX0114 in adult participants with amyotrophic lateral sclerosis (ALS).

Adenosine 2A Receptor Antagonism and AIH in ALS

The purpose of this research study is to determine the effects of a medication, istradefylline, in conjunction with breathing air with reduced oxygen for short periods of time (called acute intermittent hypoxia, or AIH), on breathing. This project will study breathing in people with amyotrophic lateral sclerosis (ALS) and unaffected, age-matched adults. Istradefylline is prescribed to increase movement in people with other neuromuscular conditions. A recently completed study found that people with ALS took deeper breaths, 60 minutes after using AIH.

A Study to Evaluate the Safety, Efficacy, and Pharmacodynamics of PLL001 in ALS Patients

FIH, Phase 1/2, multi-centre, randomised, double-blind, placebo controlled study with an optional open-label dosing extension to assess the safety, tolerability, efficacy, and Pharmacodynamics (PD) of single or multiple (up to 48 weeks QD) subcutaneous (SC) doses of PLL001 compared to placebo in subjects diagnosed with ALS.