This study is for patients that have been diagnosed with locally advanced head and neck squamous cell carcinoma. The purpose of this research study is to evaluate the effectiveness of using a combination of pembrolizumab and olaparib when given before and after standard chemoradiation therapy in treating locally advanced head and neck squamous cell carcinoma. Pembrolizumab and olaparib are drugs that are approved for treatment of different cancers including lung, head and neck, breast and prostate cancer. However, FDA has not approved use of these two drugs together in treating head and neck cancer.

Treatment will be offered in three phases. In the induction phase, participants will receive a single infusion of pembrolizumab and will take olaparib tablets twice daily for total of 21 days. Participants will move to the chemoradiation phase, where they will receive radiation therapy and chemotherapy per routine standard care, for a total of 7 weeks. Chemoradiation therapy is done on a daily basis (excluding weekends), and chemotherapy therapy will involve a cisplatin infusion once weekly. At the conclusion of this phase, participants start the maintenance phase, which involves treatment with pembrolizumab and olaparib in cycles that are 42-days long. Treatment will include a single pembrolizumab infusion during each cycle and taking olaparib tablets twice daily during each cycle. Total number of cycles to be completed in the maintenance phase are 8 cycles. Participants can expect to be in this study for about 6.5 years.

Persistent smell loss that can include diminished or distorted smell function is a common symptom of long COVID syndrome. There are limited treatment options for long COVID-related smell loss. Our study aims to determine the efficacy of two at-home treatments, smell training and non-invasive trigeminal nerve stimulation. This study requires participants to conduct daily at-home treatment sessions, attend three in-person study visits at the MUSC Department of Psychiatry and Behavioral Sciences, and complete electronic questionnaires over the 12-week trial, and again at the six-month timepoint. Participants in this trial may benefit directly with an improvement in sense of smell. However, participation may also help society more generally, as this study will provide new information about long COVID-related smell loss and its treatment.

EEG Substudy:

Long COVID syndrome has been associated with cognitive impairment and may be related to affected emotional regulation. This study will use a electroencephalography (EEG) to examine how the body and brain responses to emotional cues in participants who are currently undergoing treatment for COVID-related smell loss. Participation will aid in the understanding of how emotional processing in long COVID is impacted by treatment for related smell loss.

Blood Analysis Substudy:
Alzheimer's Disease can be precedented by other clinical disorders or neuropsychiatric symptoms. Due to the cognitive deficits that can affect those with Long COVID, this sub study will use a blood sample to investigate if there are blood based biomarkers for Alzheimer's in those who report Long COVID symptoms.

This Phase 3 study is designed to assess the long-term safety and efficacy of lebrikizumab in participants 6 months to <18 years of age with moderate-to-severe AD. Participants who have completed Study KGBI through Week 16 without requiring the use of systemic rescue medication will be eligible to enroll into Study KGBJ. All participants will receive active lebrikizumab treatment during Study KGBJ. The planned duration of treatment for each participant is approximately 52 weeks. All participants will enter a post-treatment safety follow-up period approximately 12 weeks after the last dose of lebrikizumab. This study will include both on-site (in clinic) and remote visits (telephone calls).

This study is being done to understand whether a different type of electroencephalography (EEG) monitoring that permits longer monitoring is able to capture more seizures than regular EEG monitoring, and whether this new type of monitoring will improve clinical care. This type of EEG monitoring (REMI) is currently cleared by the United States Government Food and Drug Administration (or FDA) for use in hospitals but not yet cleared to be used at home.
Eligible subjects who have EEG monitoring scheduled with either a 3-day EEG monitoring performed at home or with a 3-day EEG monitoring schedule at the Medical University of South Carolina (MUSC). Subjects are in the study for approximately 4 weeks and will need to come to the study center for one or two visits. They will be asked to wear 4 of Epitel's REMI Sensors on their head, in addition to the regular EEG electrodes, for two 2-week REMI EEG monitoring periods. A 2nd visit (clinic visit) at MUSC may be needed if the recording is at MUSC, in order to start the second REMI EEG monitoring session.
At the end of the study, three independent epileptologists will review the REMI EEG recordings and compile a report of any findings. They will then provide this report to the subject's neurologist who will assess the value of the additional EEG information, and save the report within the MUSC medical record.

The purpose of this study is to identify whether investigational blood and tissue testing can detect cancer cells in the blood stream can tell if subjects are responding to their individual treatment plans.

Participation will last as long as the subject's individual treatment plan and will consist of collecting tissue biopsies (10 slides), which will be taken during the subject's standard of care procedure, as well as blood draws (between 1 and 2 tablespoons), which will be taken during each of the subject's standard of care clinic appointments throughout their care journey.

5-aminosalicylic acid (5-ASA) medications are first line treatment for mild to moderate Ulcerative Colitis (UC), comprise 81% of all UC prescriptions, and have a market share of 1.5 billion. However, despite 5-ASA frequency and optimization, 35% of patients fail induction therapy and 52% of patients fail to maintain remission at 12 months, requiring step up therapy to immunomodulators or biologics which have increased side effects and cost. This highlights a key challenge in UC which is to address the large inter- and intrapatient variabilities in both disease progression and variability in response to treatment. Chronotherapy is the timing of medical interventions according to the host circadian rhythms in order to optimize drug response and minimize toxicity, and is one explanation for the large variability in response to medications. The long-term objective of our research is to establish the hypothesis that is that appropriate time of day of administration of oral, once daily 5-ASA therapy in alignment with the host circadian rhythms will improve subclinical inflammation and microbial structure/function and increase mucosal 5-ASA levels. To test this hypothesis, In
response to the small R01 for pilot and feasibility clinical trials (PAS-20-160) and to test our hypothesis, we propose to conduct a six month, single center, randomized crossover pilot trial involving 60 subjects with inactive UC [Mayo score ≤2, endoscopic score 0-1] but subclinical inflammation [stool calprotectin > 50 mcg/g] on a stable dose of once daily 5-ASA medication. All subjects will be randomized to once daily 5-ASA medications two different times of the day: either between 06:00 – 10:00 h or 18:00 – 22:00 h. Three disease assessments will performed at: 1) enrollment just before randomization; 2) month 3, at the completion of first arm (condition 1), and 3) month 6, after completion of the second arm (condition 2). We will assess time impact of our chronotherapy protocol on: 1) subclinical inflammation (Aim 1): a) stool calprotectin; b) intestinal barrier integrity; and c) endoscopic/histology scores; 2) Microbiota: mucosal and stool microbiota structure and function (Aim 2); and 3) 5-ASA metabolism: a) increase mucosal levels of 5-ASA and b) mucosal NAT activity (Aim 3). In addition, optimal 5-ASA treatment (i.e., Aims 1-3) will depend upon host chronotype which will be monitored by validated questionnaires, rest-wake actigraphy, and urinary melatonin. The results of this innovative proposal will establish a key role for chronotherapy in the treatment of UC and provide pilot data for the future larger multicenter clinical trials. Chronotherapy will allow for a personalized medicine approach that incorporates circadian biology to improve efficacy and minimize intolerance in treatment of UC.

This study is designed to learn about the safety and effectiveness of a new gene therapy called KB408 for Alpha-1 Antitrypsin Deficiency (AATD). AATD is an inherited condition in which a person has low blood levels of a protein known as alpha-1 protease inhibitor (called Alpha1-PI). AATD causes an increased risk of chronic obstructive pulmonary disease (COPD) in the form of emphysema (long term lung disease) and, less frequently, other diseases.
KB408 delivers copies of the genes that produce AAT to the lungs and is given by inhaling a mist (called nebulization). The genes are carried and delivered by a modified herpes simplex virus type 1 (HSV-1). This virus is not harmful and simply acts as a vehicle to deliver the genes to the lungs. The genes that are delivered by KB408 do not change a person's own DNA. This is an open-label study, meaning that the participants, the study doctor, and the sponsor all know that the participants are receiving KB408. KB408 is an investigational product, meaning it is not approved for commercial use by the FDA.
Eligible participants will receive one of three doses of KB408. Participants will have a screening visit first to make sure that they are able to participate in the study. After the screening visit, participants will need to return to the study center for follow up visits. The number of follow up visits depends on which cohort the subject is enrolled in. At the second visit, participants will receive the study drug. In Cohort 2b, subjects will have repeat dosing. Each visit will take between 2 and 8 hours to complete. Study procedures include medical history collection, vitals, physical exam, ECG, spirometry and DLCO, urine cotinine test, blood work, cheek swab, sputum sample, and bronchoscopy.
Possible side effects of KB408 include temporary increases in certain cell types in the lungs and temporary increases in the breathing rate after dosing. Since this is the first time that KB408 has been given to humans, it is possible that participants may have an immune reaction to the study drug. There is also a risk with genetic testing and a risk to confidentiality. Participants may not receive any personal benefit from being in this study. There is no guarantee that the Study Drug will help. The information that is collected from the study may help other people in the future.

This project is being conducted in subjects that have been diagnosed with myelodysplastic syndromes (MDS), MDS/myeloproliferative neoplasms (MPN) including chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML) who are candidates to receive treatment with single agent azacitidine based on local country approvals and/or local The study is designed to move efficiently from Phase 1 to Phase 3. This study is testing investigational drug called ASTX030. Investigational means that it is not approved by the Food and Drug Administration (FDA), but it is undergoing testing to find out if it is safe and effective. ASTX030 is a combination of two medicines, azacitidine and cedazuridine, given by mouth. The primary purpose is to test the levels of the investigational drug ASTX030 in your blood, including if food has an effect (Phase 1B only), the safety and tolerability of the drugs, and how subjects respond to the drug. The subject may remain in the study about 3 years. If you benefit from treatment, you may receive study drugs as long as you continue to benefit. If you develop side effects to the study drugs that prevent you from continuing treatment, or if your study doctor believes it is in your best interest to stop the study drug(s), you may be asked to stop the study treatment. After you stop treatment, the Sponsor will continue to collect health information to evaluate long-term effects of the study drugs.

This study aims to investigate innovative approaches to managing chronic pain and opioid use. This study consists of two phases, each offering different treatment options. Participation is voluntary.

This study will sequentially evaluate three novel and scalable interventions for at-risk individuals on long term opioid therapy for chronic pain: (1) low-dose transdermal buprenorphine initiation without a period of opioid withdrawal; (2) a brief Cognitive Behavioral Intervention for pain (CBI); and (3) transcranial magnetic stimulation by examining standardized repeated measures of clinical outcomes at baseline, during treatment, and at follow-up.

Phase 1:
In this initial phase, all participants will have a 1-week open-label trial of buprenorphine (worn as a patch on the arm, shoulder or upper-back). This trial aims to assess the safety and effectiveness of buprenorphine in managing chronic pain and opioid use. During this phase, participants will have the opportunity to experience the effects of buprenorphine under close monitoring.

Phase 2:
After completing Phase 1, participants will have the opportunity to choose their next course of treatment. They can decide to continue with buprenorphine, and undergo a 1-week trial of either real buprenorphine or a placebo (an inactive substance). They will be randomly assigned to receive either real or placebo buprenorphine. If participants respond well to buprenorphine treatment, they may continue the medication under the care of their physician.

Alternatively, participants can explore an alternative treatment called repetitive transcranial magnetic stimulation (rTMS) in Phase 2. If they opt for rTMS, they will receive either real rTMS or a sham version interspersed with cognitive-behavioral therapy for pain. Participants will be randomly assigned to receive either real or sham rTMS.

In both phases, participants will receive close monitoring and attend regular study visits to assess safety and progress. Throughout the study, they will be asked to complete questionnaires about pain, functioning and opioid use, undergo physiological monitoring and blood samples will be collected at specific points.

It's important to note that there are potential risks associated with the study medication, such as difficulty sleeping, nausea, and dizziness. Additionally, for the rTMS arm, there is risk of mild headache, pain at the stimulation site, and there may be unknown risks related to the brain stimulation.

Participants' experience in Phase 1 will involve an open-label trial of buprenorphine, and participants' decisions in Phase 2 will determine the treatment path. While the effectiveness of these treatments is uncertain, participants will receive thorough monitoring throughout the study, and have the option to withdraw at any time. Improvement in participant symptoms is possible but not guaranteed.

The study is being conducted in order to assess the long-term safety of rocatinlimab in adult and adolescent subjects with moderate-to-severe atopic dermatitis (AD). The study population will include subjects who completed an end of treatment duration visit in a parent study and meet eligibility criteria. Subjects will be randomized to receive a dosage of rocatinlimab based on age and their previous dosage from the parent study. The total duration of participation, including the parent study, will be up to 2.5 to 3 years, with a safety follow-up period after the last dose of investigational product at week 104.