Office of Research
Clinical Trials

Testing the Use of Chemotherapy After Surgery for High-Risk Pancreatic Neuroendocrine Tumors

This phase II trial studies the effect of capecitabine and temozolomide after surgery in treating patients with high-risk well-differentiated pancreatic neuroendocrine tumors. Chemotherapy drugs, such as capecitabine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving capecitabine and temozolomide after surgery could prevent or delay the return of cancer in patients with high-risk well-differentiated pancreatic neuroendocrine tumors.

This study may be appropriate for those with: Newly Diagnosed Cancer

Study of Biomarkers in Neurodegenerative Diseases

The purpose of this study is to assess the extent to which genetic and biological/molecular abnormalities may affect different patterns of symptoms within neurodegenerative conditions, namely PD/PD-like and AD/AD-like diseases. Patients will be followed annually after a comprehensive baseline visit.

INDICT

The goal of acute TBI treatment is to minimize secondary damage that evolves over hours to days after the primary injury. Until now, however, there have been no methods for monitoring heterogeneous pathologic mechanisms to identify patients for appropriate neuroprotection therapies. Using invasive monitoring, investigators have documented that spreading depolarizations (SD), a cytotoxic dysfunction of cerebral gray matter that has been well-characterized through 60 years of research in animal models, are the dominant pathophysiologic process in peri-lesion cortex of many, but not all, severe TBI patients. Furthermore, it was found that the occurrence of SD as a secondary injury process in patients is an independent predictor of worse neurologic outcomes. Thus, monitoring of SD as a heterogeneous mechanism in TBI may allow selective use of therapy in only those patients who might benefit. Here the investigators will conduct a randomized Phase 2 feasibility trial that uses real-time SD monitoring to guide implementation of a tier-based protocol of intensive care therapies aimed at SD suppression. The study is based on the hypothesis that outcomes from severe TBI can be improved by targeting intensive care therapies to suppress the pathology of SDs as a brain marker and mechanism of secondary injury. The objective of this study is to test the feasibility of this approach to intensive care management of severe TBI in a Phase 2 trial that uses real-time SD monitoring to guide administration of prescribed therapies to suppress SD. The aims are to (1) determine the feasibility of real-time SD monitoring to guide intensive care management of severe TBI, and (2) determine the effect of SD-guided vs. standard care management to reduce secondary brain insults in severe TBI. This is a randomized Phase 2 clinical trial enrolling approximately 72 patients at 3 sites. Patients requiring neurological surgery for emergency treatment of TBI will be enrolled. The need for surgery allows for the placement of an electrode strip on the brain during surgery for subsequent electrocorticography (ECoG). ECoG data will be monitored continuously in real-time for the occurrence of SDs during intensive care. When SDs are observed, these patients (~60%, or n=43) will be randomized 1:1 to either standard (control) or SD-guided care. In the standard care arm, treatment will follow local and national guidelines with blinding to further ECoG results. In the SD-guided arm, treatment will follow a tiered-based protocol with escalation and de-escalation based on efficacy to suppress further SD pathology. Treatments will include use of ketamine sedation and adjusted targets for plasma glucose, cerebral perfusion pressure, temperature, and end-tidal CO2. As outcomes, the accuracy of real-time SD scoring and compliance with protocol tier assignment and therapy implementation will be assessed. The burden of SD pathology, other measures of cerebral physiology (intracranial and cerebral perfusion pressures, and brain oxygenation), and medical complications will also be compared between the two study arms.

DNTH103 for Multifocal Motor Neuropathy

This is a Phase 2 randomized, double-blind, placebo-controlled study testing DNTH103 in adults with multifocal motor neuropathy (MMN). The main goals are to check safety and tolerability, measure drug levels and immune response, and see whether DNTH103 helps maintain or improve muscle strength and function. Participants who meet criteria and have a history of responding to immunoglobulin (Ig) will be randomized to receive DNTH103 or placebo. The study measures include adverse events, time until next Ig treatment, grip strength, muscle strength scores, disability and quality-of-life scales, hand dexterity tests, and blood tests for drug levels and antibodies. The controlled treatment period is through Week 17, with an optional open-label extension up to Week 52. People with major medical problems, certain prior treatments, active infections, other autoimmune diseases, recent cancer, or other factors that could affect safety or outcomes are excluded.

Early Neuromodulation TBI Recovery

This study tests whether a short, noninvasive brain stimulation given early after a moderate to severe traumatic brain injury (TBI) helps thinking and memory as the brain heals. The study will enroll about 60 adults who had an isolated moderate or severe TBI. At the first (acute) visit while still in the hospital, participants complete a short thinking test and two computer tasks while their brain waves are recorded with EEG. Half will be randomly chosen to get 15 minutes of active anodal transcranial electrical stimulation (A-tES) to the left front part of the brain while doing the tasks; the other half will get a sham (placebo) stimulation. Everyone is followed for 6 months. At about 3 months they return for testing and all receive active A-tES during tasks. At 6 months they do testing with EEG but no stimulation. The study aims to (1) find brainwave patterns that track recovery from acute to chronic stages of TBI and (2) test whether giving A-tES early improves task performance, cognitive test scores, and quality of life at 6 months compared with giving stimulation only at 3 months. The study uses a randomized, double-blind, sham-controlled design for the early stimulation comparison.

Using Voice Recordings to Measure Lung Function

This research is studying whether simple voice recordings, like counting out loud or holding a sound, can help measure lung function. It includes adults with neuromuscular diseases and healthy volunteers. These voice tests may help doctors monitor breathing when standard lung tests are difficult or unavailable.

Understanding Swallowing Exercises

Healthy adults complete swallowing and tongue exercises during a single x-ray swallow study visit. The goal is to understand how these exercises move swallowing muscles.

Studying a Switch in Treatment for Relapsing Multiple Sclerosis

This study is testing whether a daily oral medicine called remibrutinib works as well as the current treatment, ocrelizumab, for people with relapsing multiple sclerosis. People who have been on ocrelizumab for at least 18 months and are between 40 and 70 years old may join. The study will look at how MS changes over time using MRI scans, physical tests, and symptom reports. Participants may receive remibrutinib or continue ocrelizumab for up to two years, and those who finish this part may continue on remibrutinib for another two years. The study aims to learn whether switching to remibrutinib is safe, effective, and easier for patients.

KarXT for Teen Schizophrenia

This is a randomized, double-blind, placebo-controlled Phase 3 study testing KarXT in adolescents (13–17 years) with schizophrenia. After screening and confirmation of diagnosis, participants are randomly assigned to receive KarXT or placebo. The main goal is to see if KarXT reduces psychotic symptoms compared with placebo after about five weeks of treatment. Safety and overall clinical improvement will also be measured. The study checks symptom scales and global functioning during the treatment period. People with other major psychiatric disorders, significant medical or neurological conditions, known intellectual disability, severe liver problems, or very high blood pressure are not eligible.

Brain MRI in Adults with Sickle Cell Disease

The purpose of this study is to see whether inflammation is present in the brains of people with sickle cell disease and whether this inflammation may be a cause of decreased cognition (ability to learn/remember) in people with sickle cell disease. Brain images from people with sickle cell disease will be compared to brain images from people without sickle cell disease.

Pramipexole vs Escitalopram Study

This is a Phase 2, open-label randomized trial that will compare two medicines for depression in people living with HIV: pramipexole extended release and escitalopram. Participants will be randomly assigned to one of the two treatments and followed for about 24 weeks. Study visits will check how participants are feeling, measure depression and thinking skills, and watch for side effects. A smaller optional sub-study will collect and study spinal fluid in up to 36 people to see how treatment affects brain inflammation markers.

SPARX3

This study is a Phase III multi-site, randomized, evaluator-masked, study of endurance exercise on 12 month, 18 month, and 24 month changes in the MDS-UPDRS Part III score. 370 participants will be randomly assigned to 2 groups: 1)60-65% HRmax and 2)80-85% HRmax 4 times per week. Secondary aims will test hypotheses related to ambulatory mobility, daily activity, cognition, fitness, quality of life, measures of dopaminergic neuronal integrity and blood-derived biomarkers of inflammation and neurotrophic factors.

Youth Weight Gain OLZ SAM vs Olanzapine

This is a 52-week, randomized, double-blind study in children and teens with schizophrenia or bipolar I disorder. Participants will get either OLZ/SAM (olanzapine combined with samidorphan) or olanzapine alone. The main goal is to compare weight change using BMI Z-score at 12 weeks. The study also looks at how many kids have a meaningful BMI Z-score increase, waist size, symptom scores for schizophrenia or bipolar disorder, time until they stop the study drug, and any side effects up to 52 weeks. Eligible participants are aged 13-17 for schizophrenia or 10-17 for bipolar I, are outpatient-capable, have caregiver support, and are either on olanzapine now or had a poor response to another antipsychotic. People are not allowed in the study for reasons such as certain other psychiatric or neurologic problems, recent opioid use, recent olanzapine exposure or poor response, extreme BMI, diabetes or recent changes in weight programs. Safety and symptoms will be checked regularly during the study.

New Treatments for Recurrent Glioblastoma

This clinical trial studies new drug combinations for treating people with recurrent glioblastoma, a type of brain cancer that has returned. The trial is testing whether the combination of two monoclonal antibodies, relatlimab and nivolumab, can be as effective or more effective than the current standard treatment, lomustine. These drugs work by potentially interfering with the ability of tumor cells to grow and spread. Participants will be randomly assigned to receive either the experimental drug combination or the standard chemotherapy drug. They will undergo regular checks, including MRI scans and biopsies, to track their response to treatment. The study will compare survival times and patient health outcomes between the two treatment groups over various periods up to 5 years to understand the effectiveness and safety of these treatments.

This study may be appropriate for those with: Recurrent Cancer

Ublituximab Modified Regimen Study

This Phase 3b study tests a changed dosing plan of ublituximab, a medicine that targets B cells, in people with relapsing multiple sclerosis (RMS). The study has three parts: Part A is open to eligible participants and looks at MRI brain lesions over about 48 weeks; Part B is randomized and double-blind to study drug levels and compare to placebo up to 16 weeks; Part C enrolls people who had a suboptimal experience on another anti-CD20 treatment to see how they do on ublituximab. Main goals are to see if the modified schedule prevents new gadolinium-enhancing MRI lesions and to understand the drug's blood levels. Participants have regular visits for dosing, safety checks, and MRI scans. People with active infections, certain immune diseases, prior serious infusion reactions to anti-CD20 drugs, some prior cancer or prior use of specific immunosuppressive drugs are not allowed to join.

APT Acute TBI Adaptive Multi-Arm Phase 2 Platform Trial

This is a randomized, parallel, multi-arm, multi-stage adaptive Phase 2 platform trial testing whether repurposed FDA-approved drugs given off-label soon after injury can improve recovery after acute non-penetrating traumatic brain injury (TBI). Adults 18-65 who present within 24 hours of injury with a Glasgow Coma Scale (GCS) 9-15, CT evidence of intracranial trauma (CT+), and an elevated GFAP blood level (>100 pg/mL) are eligible. Participants are randomized to one of the investigational drug arms or placebo. Investigational agents vary by arm and are selected for potential neuroprotective and anti-inflammatory effects to reduce secondary injury. Participants undergo serial clinical assessments, blood biomarker sampling (including GFAP and NfL), cognitive testing, and MRI (including DTI). The primary efficacy outcome compares change in the Glasgow Outcome Scale-Extended (GOSE) between Week 2 and Month 3. Secondary outcomes include biomarker trajectories, DTI measures, cognitive performance, and post-concussive symptom scales. Follow-up visits occur through Month 6 with approximately six in-person visits plus interim phone assessments and scheduled imaging/blood draws. Safety monitoring excludes participants with significant comorbidities, pregnancy, known contraindications to study drugs, or abnormal renal/hepatic function, among other criteria. The trial uses an adaptive platform design allowing multiple investigational arms to be evaluated sequentially or concurrently against placebo.

Improving Sleep and Thinking in People with Parkinson Disease Using Different Brain Stimulation Settings

This study is testing whether changing the settings of an implanted brain stimulation device during sleep can improve sleep quality and thinking abilities in people with Parkinson disease. Participants who already have a deep brain stimulation device will receive two different stimulation settings in a random order. One setting uses their usual stimulation day and night, while the other uses a lower setting during sleep. Participants will complete sleep questionnaires, thinking and memory tests, and movement assessments during the study. Researchers hope to learn whether nighttime brain stimulation changes can improve sleep and thinking without worsening movement symptoms.

NAC Treatment for Bipolar Offspring

This is an 8-week, open-label study testing whether daily N-acetylcysteine (NAC) helps reduce depressive symptoms in young people at high risk for bipolar disorder. Participants are 15 to 24 years old and must have a first-degree relative with Bipolar I disorder and current depressive symptoms. Each participant will have a brain scan (resting-state fMRI) at the start and end of the 8 weeks to look for changes in brain connections, especially between parts of the left front of the brain and the left striatum. The study will track mood and anxiety symptoms, overall clinical status, and whether changes in symptoms relate to changes in brain connectivity. This pilot trial aims to see if NAC is safe, well tolerated, and shows signs of benefit, to support a larger future placebo-controlled neuroimaging study.

Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/​11 Mutations or PRKC Fusions

This is a Phase 1/2, multi-center, open-label basket study designed to evaluate the safety and anti-tumor activity of IDE196 in patients with solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations or PRKC fusions, including metastatic uveal melanoma (MUM), cutaneous melanoma, colorectal cancer, and other solid tumors. Phase 1 (dose escalation - monotherapy) will assess safety, tolerability and pharmacokinetics of IDE196 via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study. Phase 1 Tablet and Food Effect Pharmacokinetic (PK) Substudy will assess the PK profile of IDE196 tablet and evaluate the effects of food on the PK profile of IDE196 tablet Phase 1 (dose escalation - binimetib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and binimetinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study. Phase 1 (dose escalation - crizotinib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and crizotinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.

This study may be appropriate for those with: Metastatic Cancer

Riliprubart for Refractory CIDP

This is a Phase 3 clinical trial testing riliprubart, given to adults with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) whose disease did not respond well to usual treatments (IVIg or steroids). Participants are randomly assigned to receive riliprubart or placebo. The first part (double-blind) compares effects through Week 24 and up to Week 48 for some outcomes. After that, an open-label part allows longer treatment and safety follow-up up to a maximum of 111 weeks. The main goal is to measure how many people have meaningful improvement in disability scores (a drop of at least 1 point on the adjusted INCAT scale) by Week 24 and whether improvements last. The study also checks strength, fatigue, quality of life, side effects, and whether the body makes antibodies to riliprubart. People must meet specific diagnosis and stability rules and must not have other causes of neuropathy or recent conflicting treatments. Vaccinations and contraception rules apply.

Studying the Brains of Elite Athletes

This research study looks at how the brains of elite athletes may be different from others. Participants complete advanced brain scans that measure brain structure and brain activity while resting and performing simple tasks. The goal is to understand how years of intense training may shape the brain and support high-level athletic performance. The study involves one short visit, or two shorter visits, and does not involve treatment or changes to medical care.

STRATEGY FOR IMPROVING STROKE TRMT RESP

SISTER is a Phase-2, prospective, randomized, placebo-controlled, blinded, dose finding trial that aims to determine the safety and preliminary efficacy of TS23, a monoclonal antibody against the alpha-2 antiplasmin (a2-AP), in acute ischemic stroke.

Subcutaneous weekly injection by autoinjector for Generalized Myasthenia gravis

Study IMVT-1402-3101 is a Phase 3, multicenter, randomized, placebo-controlled, double-blind study to assess the efficacy, safety and tolerability, PK, and PD of IMVT-1402 in participants 18 to 80 years old inclusive who have mild to severe gMG. Eligible participants will be randomized in a 1:1:1 ratio to receive blinded IMVT-1402 600 mg subcutaneous (SC) once weekly (QW), IMVT-1402 300 mg SC QW, or placebo SC QW for 12 weeks during Period 1

Ultrasound to Study Swallowing Problems

Adults aged 50 or older referred for a swallow test may participate in a study using ultrasound alongside standard X-ray tests. Some may also try ultrasound feedback during therapy.

Oral Cladribine in Generalized MG

This is a Phase 3 study testing a new oral form of cladribine in adults with generalized myasthenia gravis (gMG). Participants are randomly assigned to receive the new cladribine or placebo during a 24 week double blind period. The study then continues into two extension periods to see how long benefits last, whether people need retreatment, and to monitor long term safety. The main measure is change in daily function using the MG-ADL score at 24 weeks. Other measures include muscle strength scores, quality of life, time to first retreatment, safety events, lab tests (including lymphocyte counts), and drug levels in the blood. People must have stable MG symptoms and medications before joining. Important exclusions include other immune or neuromuscular diseases, active infections, cancer, recent use of many other immune drugs, prior cladribine use, and lack of varicella immunity. The study aims to show whether oral cladribine can safely reduce MG symptoms and how long the effect lasts.