Clinical Trials

The Neurology Department is dedicated to advancing research in the prevention, detection and treatment of neurological diseases in areas such as Movement/Parkinson’s, Epilepsy, Multiple Sclerosis, and Neuromuscular disorders. We have numerous clinical trials currently being conducted to help us do just that. If you or anyone you know would be interested in participating in one of these clinical trials, please contact us at neurotrials@neurology.wisc.edu or 608-263-5421. To view a full listing of our clinical trials, search clinicaltrials.gov.

CHILD NEUROLOGY

Prospective Long-Term Registry of Patients with a Diagnosis of Spinal Muscular Atrophy (SMA)

Researcher:	Jennifer Kwon, MD
Sponsor:	AveXis, Inc.
Protocol No:	AVXS-101-RG-001
IRB No:	2018-1013
Objective:	The purpose of this registry is to assess the long-term outcomes of participants with SMA in the context of advances in treatment options.
Description:	Your child will not be asked to come for any additional clinical visits or have any other laboratory tests done as part of participation in this registry. All data that is collected as part of this registry is taken from the information your child’s study doctor has documented in their medical notes during their normal doctors’ visits, questionnaires for the study that you will be asked to complete during your normal doctors’ visits, as well as tests that were performed during these visits. SMA treatments will be reviewed to see what effect they have on your child as follows:–To assess the effectiveness of treatments for SMA –To assess long-term safety –To assess overall survival of all subjects with SMA –To assess healthcare utilization –To assess caregiver burden –To assess participant functional independence Information about your child’s SMA treatment will be collected for the registry for a period of up to 15 years.
Key Eligibility:	Participants must meet the following criteria;–Subjects with genetic confirmation of SMA
Compensation:	You/your child will be compensated $25 as reimbursement for your time completing the questionnaires and travel related to participation in the registry.
Site Contact:	Neurology Trials
Link	clinicaltrials.gov

Early Biomarkers Study for Prediction of Executive Dysfunction and Cognitive Outcomes Among Healthy Infants and Infants with Prior Neonatal Brain Injuries

Researcher:	Melisa Carrasco McCaul
Sponsor:	Thrasher Early Career Award, Centennial Scholars Program
IRB No.:	2021-1625
Description:	This is a prospective, observational cohort study to examine early biomarkers for executive dysfunction and cognitive disability in infants with and without perinatal brain injury.
Objective:	The purpose of the study is to evaluate new methods for assessing risk for executive function and cognitive disability in healthy infants and infants (<24 months of age) with a known history of perinatal brain injury secondary to hypoxic ischemic encephalopathy (HIE), perinatal stroke (PS), neonatal seizures (NS), or premature gestation (PG).
Key Eligibility:	Healthy infants and newborns with perinatal brain injury meeting inclusion criteria: those diagnosed during the neonatal period with hypoxic-ischemic encephalopathy, perinatal strokes, neonatal seizures, premature gestational age (born at less than 32 weeks gestational age), having required a cardiac procedure and/or ECMO during the neonatal period.
Compensation:	Visit 1 – $100, Visit 2 – $75, Visit 3 – $75.
Link:	https://neurology.wisc.edu/research-and-labs/trees-lab/, T.R.E.E.S. Participant Flyer May 2023 Updated
Site Contact:	neurotrials@neurology.wisc.edu

Virtual Abecedarian Approach (A2) For IPNH-NDCP (Infants with Perinatal Neurological Histories – At Risk for Neurodevelopmental Disabilities or Cerebral palsy)

Researcher:	Melisa Carrasco McCaul
Sponsor:	UW Institute for Clinical and Translational Research (ICTR)
IRB No.:	2024-1658
Objective:	To address the feasibility of the Virtual A2 intervention, as well as associated compliance and parent satisfaction.
Description:	This study examines a new special program, the Virtual Abecedarian Approach (Virtual A2), in developing improved cognitive (learning) skills in very young children, ages 6 months to 5 years. The program is meant to help children who may have had health problems that could affect how their brain works or make it harder for them to learn, as can be the case in some children who were born extremely premature or who were diagnosed with hypoxic-ischemic encephalopathy at birth. To achieve this goal, pairs of parent-children will be recruited and randomly assigned to the Virtual A2 intervention vs the control group intervention, by chance.
Key Eligibility:	IPNH-NDCP patients, including:
	Term-born children diagnosed during the neonatal period with hypoxic-ischemic encephalopathy, or Premature children (born at less than 28 weeks gestational age).
	Premature children (born at less than 28 weeks gestational age).
	A parent or legal guardian will also be enrolled as a participant.
Compensation:	Participants will receive compensation annually after completing their Follow-Up Assessment Visits ($100) and children will receive a small toy valued at less than $10.
Link:	ClinicalTrials.gov
Site Contact:	neurotrials@neurology.wisc.edu

EPILEPSY

NEUROMUSCULAR

PEDIATRICS

MOVEMENT DISORDERS

Trial of Parkinson’s And Zoledronic Acid (TOPAZ)

Researcher:	Dr. Kathleen Shannon
Sponsor:	National Institute of Aging
IRB No.:	1928009
Objective:	The primary aim of the study is to evaluate the efficacy of a single infusion of zoledronic acid (ZA, 5mg) to reduce the risk of clinical fractures in Parkinson’s Disease or neurodegenerative parkinsonism.
Description:	This home-based randomized clinical trial is designed to test the efficacy of ZA-5 mg in Parkinson’s disease (PD) and parkinsonism patients. This trial will also address barriers to treatment of patients with PD and parkinsonism by providing rigorous evidence about whether ZA reduces fracture risk in patients with PD and parkinsonism, simplifying treatment by giving ZA at home without extra medical visits and BMD testing, and overcoming poor persistence with oral therapies because one infusion may prevent bone loss for at least 2 years. The outcome of this trial will demonstrate how a home-based fracture prevention can reach older PD patients who would not otherwise receive treatment to reduce their high risk of fractures. Patients with PD will be recruited throughout the US by participating neurologists and health networks as well as the Parkinson’s Foundation. Patients may also self-refer to the study. Interested patients can access study information on a study website (topaz.eurekaplatform.org) as well as through the Parkinson’s Foundation Helpline. Patients who wish to enroll will be directed to an interactive electronic consent (eConsent). Following eConsent, participants complete a screening questionnaire (to confirm eligibility), followed by a baseline questionnaire. If a participant is determined to be eligible following these steps, they may be scheduled for a Telemedicine assessment to further confirm the PD or parkinsonism diagnosis, unless they have been referred directly from a participating neurologist. If confirmed, the participant will be mailed a supply of vitamin D3 800-1000 IU and instructed to take one vitamin D tablet every day for 2 months. Lastly, a Nurse Home Visit will be scheduled and conducted to confirm final eligibility, randomization, and administration of the study drug, if appropriate. Participants who are randomized will be contacted every 4 months for at least 2 years to determine if they have had any fractures.
Key Eligibility:	Men and women age 60 or older Current Parkinson’s Disease or neurodegenerative parkinsonism diagnosis (including progressive supranuclear palsy, multiple system atrophy, cortical basal degeneration, vascular parkinsonism, dementia with Lewy bodies or another form of neurodegenerative parkinsonism) Willing and able to continue in follow-up for at least 2 years Willing and able to provide informed consent
Compensation:	Participants who complete a Nurse Home Visit and are randomized will be offered an honorarium (for time and effort) of a $100 gift card, a $50 gift card upon completion of the measures in the 1st year of follow-up (through Month 12), another $50 gift card upon completion of the measures in the 2nd year of follow-up (through Month 24), and a $50 gift card for each completed year of follow-up thereafter, as appropriate.
Link:	clinicaltrials.gov
Site Contact:	neurotrials@neurology.wisc.edu

Enroll-HD: A Prospective Registry Study in a Global Huntington’s Disease Cohort

Researcher:	Dr. Kathleen Shannon
Sponsor:	CHDI Foundation
IRB No.:	2021-0877
Objective:	The primary objective of Enroll-HD is to develop a comprehensive repository of prospective and systematically collected clinical research data (demography, clinical features, family history, genetic characteristics) and biological specimens (blood) from individuals with manifest HD, unaffected individuals known to carry the HD mutation or at risk of carrying the HD mutation, and control research participants (e.g., spouses, siblings or offspring of HD mutation carriers known not to carry the HD mutation). Enroll-HD is conceived as a broad-based and long-term project to maximize the efficiencies of non-clinical research and participation in clinical research. With 158 active clinical sites in 19 countries, Enroll-HD is now the largest HD database available and is accessible to any interested researcher – visit www.enroll-hd.org/for-researchers/access-data/ to learn more.
Description:	Enroll-HD is a longitudinal, observational, multinational study that integrates two former Huntington’s disease (HD) registries-REGISTRY in Europe, and COHORT in North America and Australasia-while also expanding to include sites in Latin America. More than 20,000 participants have now enrolled into the study. With annual assessments and no end date, Enroll-HD has built a large and rich database of longitudinal clinical data and biospecimens that form the basis for studies developing tools and biomarkers for progression and prognosis, identifying clinically-relevant phenotypic characteristics, and establishing clearly defined endpoints for interventional studies. Periodic cuts of the database are now available to any interested researcher to use in their research – visit www.enroll-hd.org/for-researchers/access-data/ to learn more.
Key Eligibility:	Carriers: This group comprises the primary study population and consists of individuals who carry the HD gene expansion mutation.
	Controls: This group comprises the comparator study population and consists of individuals who do not carry the HD expansion mutation
	These two major categories can be further subdivided into six different subgroups of eligible individuals:
	Manifest/Motor-manifest HD: Carriers with clinical features that are regarded in the opinion of the investigator as diagnostic of HD.
	Pre-Manifest/-Motor-manifest HD: Carriers without clinical features regarded as diagnostic of HD.
	Genotype Unknown: This group includes a first or second degree relative (i.e., related by blood to a carrier) who has not undergone predictive testing for HD and therefore has an undetermined carrier status.
	Genotype Negative: This group includes a first or second degree relative (i.e., related by blood to a carrier) who has undergone predictive testing for HD and is known not to carry the HD expansion mutation
	Family Control: Family members or individuals not related by blood to carriers (e.g., spouses, partners, caregivers).
	Community Controls: Individuals unrelated to HD carriers who did not grow up in a family affected by HD. Data collected from community controls will be used for generation of normative data for sub-studies.
Compensation:	You will not receive payment for participating in Enroll-HD. There is also no cost for the research evaluations performed during this research study. Study participants are eligible for a payment to defer the cost of travel.
Link:	ClinicalTrials.gov
Site Contact:	neurotrials@neurology.wisc.edu

A Study of AAV2-GDNF in Adults with Moderate Parkinson's Disease (REGENERATE-PD)

Researcher:	Dr. Kathleen Shannon
Sponsor:	Asklepios BioPharmaceutical (AskBio)
Protocol No.:	Ask-PD5-CS201
IRB No.:	2024-1320
Objective:	To evaluate the efficacy of AAV2-GDNF to improve or stabilize motor symptoms in subjects with moderate Parkinson’s Disease.
Description:	Testing an experimental treatment called glial cell line-derived neurotrophic factor (GDNF) gene transfer to see if it helps people with Parkinson’s Disease (PD). GDNF gene therapy (AAV2-GDNF) is delivered to a part of the brain involved in PD. This study will evaluate the efficacy and safety of this study treatment and see whether it can improve the course of moderate PD.
Key Eligibility:	Male and female adults 45-75 years of age inclusive, at the time of signing the informed consent.
Key Eligibility:	Diagnosed with Parkinson’s Disease in the past 4 to 10 years (inclusive) as defined by the presence of bradykinesia plus rigidity, rest tremor and/or postural instability.
Link:	ClinicalTrials.gov
Site Contact:	neurotrials@neurology.wisc.edu

STROKE

MULTIPLE SCLEROSIS

Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis

Researcher:	Natasha Frost
Sponsor:	Novartis Pharmaceuticals
Protocol No.:	CLOU064C12301
IRB No.:	2022-1707
Objective:	To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with relapsing multiple sclerosis
Description:	The study CLOU064C12301 consists of an initial Core Part (CP) (maximum duration per participant of up to 30 months), followed by an Extension Part (EP, of up to 5 years duration) for eligible participants. The Core Part is a randomized, double-blind, double-dummy, active comparator-controlled, fixed-dose, parallel-group, multi-center study in approximately 800 participants with relapsing multiple sclerosis (RMS). The Extension Part is an open-label, single-arm, fixed-dose design in which eligible participants are treated with remibrutinib for up to 5 years.
Key Eligibility:	18 to 55 years of age
	Diagnosis of RMS according to the 2017 McDonald diagnostic criteria
	At least: 1 documented relapse within the previous year. OR 2 documented relapses within the previous 2 years, OR 1 active Gadolinium (Gd)-enhancing lesion in the 12 months
	EDSS score of 0 to 5.5 (inclusive)
	Neurologically stable within 1 month
Compensation:	You will be reimbursed according to the following schedule: Up to $52.00 will be reimbursed for each completed visit except for Day 1 and Months 1, 6 and 12. Up to $75.00 will be reimbursed for each of those 4 completed visits.
Link:	ClinicalTrials.gov
Site Contact:	neurotrials@neurology.wisc.edu

HEADACHE

Randomized Study in Children and Adolescents With Migraine: Acute Treatment

Researcher:	Ali Zandieh
Sponsor:	Biohaven Pharmaceutical Holding Company Ltd
Protocol No.:	BHV-3000-311
IRB No.:	2022-1625
Objective:	The purpose of this study is to test the safety and efficacy of BHV-3000 versus placebo in the acute treatment of moderate or severe migraine in children and adolescents.
Description:	Biohaven Pharmaceuticals (Biohaven) is studying a drug called rimegepant as a possible treatment for migraine in children and adolescents. This drug has been approved by the United States (US) Food and Drug Administration (FDA) for treatment of migraine in adults but is considered investigational in this study because it has not been approved for use in children and adolescents for migraine. For this study, researchers would like to see whether rimegepant is effective and safe for treating migraine in children and adolescents between the ages of 12 and 17 years.
Key Eligibility:	History of migraine (with or without aura) for > 6 months before Screening according to the IHS Classification ICHD-319 specifications for pediatric migraine
	History of 1 to 8 moderate or severe attacks per month during the 2 months prior to enrollment, with attacks lasting > 3 hours without treatment, and attacks occurring at intervals > 24 hours.
	Prophylactic migraine medication are permitted if the dose has been stable for at least 12 weeks prior to the Baseline Visit, and the dose is not expected to change during the course of the study. a. Participants may remain on one (1) medication with possible migraine prophylactic effects, excluding CGRP antagonists [biologic or small molecule], during the treatment phases. b. Concomitant use of a CGRP antagonist, such as erenumab or fremanezumab, is prohibited. c. Previously discontinued prophylactic migraine medication must have done so at least 90 days prior to the Screening Visit.
	Verbally distinguish between migraine and other types of headaches.
	Participants must have a weight > 40 kg at the Screening Visit.
	Adequate venous access for blood sampling.
	Male and female participants ≥ 12 to < 18 years of age (participants must not reach their 18th birthday during the study).
Compensation:	Parents/guardians will be paid $50.00 for each completed visit up to $200.00. Your child will also be paid a total of $150.00 for a completed eDiary.
Link:	ClinicalTrials.gov
Site Contact:	neurotrials@neurology.wisc.edu

Long-term Safety Study of Rimegepant in Pediatric Subjects for the Acute Treatment of Migraine

Researcher:	Ali Zandieh
Sponsor:	Biohaven Pharmaceuticals, Inc.
Protocol No.:	BHV-3000-312
IRB No.:	2022-1624
Objective:	The purpose of this study is to test the long-term safety of rimegepant in the acute treatment of moderate or severe migraine in children and adolescents.
Description:	Biohaven Pharmaceuticals (Biohaven) is studying a drug called rimegepant as a possible treatment for migraine in children and adolescents. This drug has been approved by the United States (US) Food and Drug Administration (FDA) for treatment of migraine in adults but is considered investigational in this study because it has not been approved for use in children and adolescents for migraine. For this study, researchers would like to see whether rimegepant is effective and safe for treating migraine in children and adolescents between the ages of 12 and 17 years.
Key Eligibility:	History of migraine (with or without aura) for ≥ 6 months before Screening
	History of 1 to 8 moderate or severe attacks per month during the 2 months prior to enrollment.
	1 or more migraine days requiring treatment during the Observation Phase.
	Prophylactic migraine medication is permitted if the dose has been stable for at least 12 weeks prior to the Baseline Visit
	Ability to distinguish between migraine and other types of headaches.
	Weight ≥ 40 kg at the Screening Visit.
	Adequate venous access for blood sampling.
	Male and female participants ≥ 12 to < 18 years of age (participants must not reach their 18th birthday before enrollment into the study)
Compensation:	Parents/guardians will be paid $50.00 for each completed visit. Children will receive $250.00 for successful eDiary compliance.
Link:	ClinicalTrials.gov
Site Contact:	neurotrials@neurology.wisc.edu

GENERAL NEUROLOGY

CADASIL Consortium

Researcher:	Dr. Jane Paulsen
Sponsor:	NIH
IRB No.:	2021-1033
Objective:	The objective of the proposed research is to exploit an autosomal dominant vascular dementia as a model to investigate specific features of VCID and to examine interactions with risk factors impacting the aging life course.
Description:	The study will enroll a total of 500 participants with a CADASIL family history who have had a genetic test for a NOTCH3 variant. Participants will complete: a clinical interview, a neurological exam, neurocognitive and behavior assessments, MRI, and a blood draw at each study visit. Participants will complete 3 in-person visits in total as part of this study: baseline, visit 2 (18 months after baseline), visit 3 (36 months after baseline). Additional contact will occur by phone, mail, email or the internet and will be referred to as “remote visits”.
Key Eligibility:	Inclusion Criteria for CADASIL Participants: a) Age at least 18 years old b) positive NOTCH3* genetic testing; or a positive skin biopsy; or willingness to have a NOTCH3 genetic test prior to enrolling and are at-risk for, or diagnosed clinically, with CADASIL c) willing to commit and complete three in-person visits (baseline and 18-month follow-up and 36-month follow-up) as well as remote visits as needed by phone, email, mail or internet. d) All medications will be allowed although the protocol will mandate documentation of medications and our analyses will particularly assess potential impact of medications on outcomes . e) Able to undergo an MRI scan and blood draw at each visit f) A study companion who knows the participant well (>= 3 hours/month of contact) and can provide additional information (either remotely or in-person) g) A functional capacity equivalent to less than 4 on the Modified Rankin Scale.Inclusion Criteria for Healthy Controls (HC) a) Will meet same criteria as CADASIL participants except are or were at risk for CADASIL but have Negative NOTCH3* genetic testing
Compensation:	Participants will be reimbursed for each part of the study they complete. • Clinical assessment and completion of other study forms (remote and/or in-person): $25 per visit • MRI scan: $50 per visit • Blood draws: $25 per visit Travel, lodging, and meals will either be provided, or participants may receive partial or complete reimbursement. In addition, airport shuttle, parking, mileage, and tolls may be provided or reimbursed to the participant when applicable.
Link:	clinicaltrials.gov
Site Contact:	neurotrials@neurology.wisc.edu

Measuring Brain Complexity to Detect and Predict Recovery of Consciousness in the ICU (COMPASS)

Researcher:	Melanie Boly
Sponsor:	Mass General Brigham
IRB No.:	2024-1466
Objective:	Demonstrate the diagnostic and prognostic utility of TMS-EEG in ICU patients with DoC (n=120)
Description:	Despite growing evidence that TMS-EEG is a reliable tool to detect the brain’s capacity for consciousness, TMS-EEG has not been systematically implemented or tested in the ICU for patients with Disorders of consciousness (DoC). Our long-term goal is to translate TMS-EEG to the ICU to improve the accuracy of diagnosis and prognosis for critically ill patients with DoC.
Key Eligibility:	Age greater than or equal to 18.
	Functionally independent at baseline.
	Acquired brain injury within the last 28 days.
	Disorder of consciousness, as defined by no instance of following commands (i.e., no instance of Glasgow Coma Scale motor score = 6) on two or more consecutive assessments within the past 24 hours.
Compensation:	$50 for completion of the TMS-EEG procedures in the ICU and an additional $50 for completion of study procedures at 6-month follow-up assessment
Link:	ClinicalTrials.gov
Site Contact:	neurotrials@neurology.wisc.edu