Research Studies

The goal of this clinical research study is to find the appropriate dose of LL37 that can be given to patients with melanoma. Researchers also want to learn if LL37 can stimulate the immune system to help control the disease. Study Groups: If you are found to be eligible to take part in this study, you will be assigned to a dose level of LL37 based on when you join this study. Up to 4 dose levels of LL37 will be tested. Up to 2 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of LL37 is found. Study Drug Administration: One (1) time a week for 8 weeks, LL37 will be injected into 2-4 tumors. The injections will be done in the clinic. Study Visits: Within 1 week before your first study drug injection: * You will have a physical exam. * You will have a punch biopsy of a tumor. To collect a punch biopsy, the area of skin is numbed with anesthetic and a small cut is made to remove all or part of the affected tissue. * Blood (about 1 teaspoon) will be drawn for routine tests. * The tumors will be measured and photographed. Your private areas will be covered (as much as possible), and a picture of your face will not be taken unless there are tumors on your face. On Day 1: * You will have a physical exam. * Blood (about 1 teaspoon) will be drawn for routine tests. On Day 2, you will have a punch biopsy of one of the injected tumors. At Weeks 1, 2, 3, 4, 5, 6, 7, and 8: * You will have a physical exam. * Blood (about 1 teaspoon) will be drawn for routine tests. * At Weeks 1, 3, and 5 and 7, blood (about 4 tablespoons) will be drawn to study your immune response to LL37. At Week 4, you will have a punch biopsy of one of the injected tumors and one of the tumors that you did not have an injection in. Photos of the tumors will be taken to show if the disease has responded to the study drug. At Week 8: * Photos of the LL37 injected sites will be taken to show if the disease has responded to the study drug. * You will have CT scans to check the status of the disease. Length of Treatment: You will receive up to 8 weeks of study treatment. You will be taken off study if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on the study will be over after the follow-up visits. Off-Study Visit: If you have to stop the study treatment earlier than planned because the disease got worse or you had intolerable side effects: * You will have a physical exam. * The tumors will be photographed and measured. * Blood (about 4 teaspoons) will be drawn for routine tests and to study your immune response to LL37. * You will have CT scans to check the status of the disease. * You will have a punch biopsy of one of the injected tumors. These off-study procedures will be completed within 14 days after your last dose of study treatment. You will be contacted by phone or clinic visit at 30 days (+/- 7 days) after your last dose to follow up on any drug-related toxicities which were present at the end of study. Follow-Up: Within 2 weeks after your last study drug dose and every 8-12 weeks after that, you will have scans to check the status of the disease. Your doctor will decide what type of scans you will have. After your last study drug dose, at your routine clinic visits every 3 months for 1 year, the study staff will ask you about the status of disease, if possible. If you do not plan to continue to receive medical care at MD Anderson, the study staff will contact you by phone, email, or letter to ask about the status of disease. The calls should last about 5 minutes. This is an investigational study. LL37 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work. Up to 36 participants will be treated in this study. All will take part at MD Anderson.

This is a multicenter, randomized, placebo-controlled, double-blind, Phase 2 study. Patients will be treated for a total of 12 weeks. There will be a 6 week follow-up period after the treatment period ends. Patients will be randomly assigned to low dose CJC 1295, high dose CJC 1295 or placebo. The objective is to assess and compare the efficacy, pharmacokinetics, safety, and tolerability of CJC 1295 in patients with human immunodeficiency virus (HIV) associated visceral obesity.

Assessing the Efficacy and Long-Term Safety of a 2 mg dose of TH9507, a Growth Hormone-Releasing Factor Analog, in HIV Subjects with Excess Abdominal Fat Accumulation HIV lipodystrophy affects a significant proportion of patients treated with combination antiretroviral therapy (ART) and is characterized by excess visceral fat accumulation, loss of extremity and subcutaneous fat, in association with dyslipidemia and insulin resistance. Data from the first Phase 3 multicenter, randomized, placebo-controlled trial demonstrated that daily administration of 2mg TH9507, a growth hormone releasing factor (GRF), to HIV- infected patients with excess of abdominal fat accumulation for 26 weeks resulted in decreases in visceral adipose tissue (VAT) and trunk fat, with lesser changes in limb fat and subcutaneous adipose tissue (SAT). The present study is aimed at confirming the observations made during the first Phase 3 study.

Phase I clinical trial in healthy volunteers to study safety and pharmacokinetics of BPC-157, a pentadecapeptide from gastric source. Title: Phase I, pilot study in healthy volunteers, to assess the safety and pharmacokinetics of PCO-02, which active ingredient is BPC-157, a pentadecapeptide from gastric source. Protocol Number: BPC-1A/B-1.2 Phase: I Population: Healthy subjects, males or females, between 18 and 35 years of age. Number of Sites: Single center, to be performed at Hospital Angeles, Tijuana. Duration of Study: Six months, from January 01, 2015 to Jun 30, 2015. Duration of Subject Participation: Three weeks Intervention description:The study consists of the oral administration of PCO-02 tablets, each containing 1mg of BPC-157 or placebo. There will be two different administration schemes, which have been labeled as Phase 1a and Phase 1b. * Phase 1a: Single dose administration of 1, 3 or 6 tablets of PCO-02 or placebo. * Phase 1b: Oral administration of 3 tablets of PCO-02 or placebo three times daily for 2 weeks. Study Goals:General: To assess, in healthy volunteers, the safety and pharmacokinetics of the oral administration of PCO-02, which pharmacological active product is BPC-157. * Primary: To assess the safety of the oral administration of BPC-157. * Secondary: To document the pharmacokinetics of BPC-157 after oral administration. Study Design: This is a phase-I, randomized, placebo controlled, pilot study, in which a group of 42 healthy volunteers will receive orally an active compound (PCO-02) or placebo (PCO-03) to assess safety and pharmacokinetics. Phase 1a: There will be three cohort groups, with 14 subjects each, that will receive a single oral dose of 1, 3 or 6 tablets of PCO-02, respectively or a similar dose of placebo (PCO-03). Randomization will be at a PCO-02-to-placebo ratio of 6:1 on each group, keeping a balance between men and women among groups. For this phase, subjects will be admitted to the hospital for 24 hours and will be kept fasting before and after the administration of the study medication. Serial blood and urine samples will be obtained to document pharmacokinetics of BPC-157 peptide and the subjects from all groups will be observed for AE in order to determine the study medication's safety. A week after, subjects will return for clinical assessment and laboratory blood work to continue monitoring for AE's. Also, the cohort that will receive 3 tablets will receive a second dose in a similar manner but after having had a meal. Phase 1b:This second phase will initiate only once all subjects from prior phase have completed at least one week of follow-up and that there have been no SAE's related to study medication from phase 1a. All of subjects from phase 1a will receive a single dose of 3 tablets of PCO-02 or placebo three times daily for a period of 14 days. The assignment to active (PCO-02) or placebo (PCO-02) will be the same as per the randomization for phase 1a. This phase will be performed on an ambulatory manner, with the subjects being required to return to the clinic at days 0, 7 and 14 for safety and pharmacokinetics assessment. Estimated Time to Complete Enrollment: One month Study Goals: Primary: Safety of oral administration of PCO-02, evaluated thru the systematic monitoring for adverse events during follow-up. Secondary: Pharmacokinetics of oral BCP-157 (Tmax, Cmax, T1/2, AUC) Clinical Assessment During Follow- Up: During phase 1a, subjects will be admitted to the hospital for 24 hours for monitoring adverse events and serial blood and urine sampling after a single dose of PCO-02 or placebo (PCO-03). Subjects will be discharged from the hospital on the next morning and will return a week after the initial dose for clinical assessment and laboratory blood work to continue monitoring for possible AE's. The first cohort will receive 1 tablet of PCO-02 or placebo. Increasing to the next dose requires the absence of severe adverse events related to the intervention in the previous dose cohort at one week of follow-up. If there has been no AE's related to study medication, phase 1b will be started. Initial assessment of phase 1b will be the same as the final evaluation of phase 1a. All the subjects from phase 1a will receive a single dose of 3 tablets of PCO-02 three times daily, or a similar dose of placebo (PCO-03), for a period of 2 weeks. The assignment to active compound or placebo will be the same as for phase 1a. The subject will be required to return to the clinic at days 7 and 14 for clinical, pharmacokinetics and safety assessment, including blood and urine sampling.

This study is a prospective, randomized, open-label clinical trial enrolling 66 adults with simple obesity who have not used weight-loss medications for at least 3 months. Participants will receive semaglutide, tirzepatide, or metformin for 24 weeks. Changes in "biological (epigenetic) age" will be assessed using the iWatchAge DNA methylation age test, while simultaneously monitoring improvements in aging-related biomarkers such as inflammatory factors, metabolic parameters, and body composition. The aim is to determine whether incretin-based therapies can reverse or slow obesity-related accelerated epigenetic aging and to provide new clinical evidence for interventions targeting obesity and aging.

Approximately 80 patients affected by moderate to severe psoriasis will be screened for the presence of LL37( and ADAMTSL5 autoreactive T-cells in their blood at Day 0. Patients whose lymphocytes reacted with proliferation to LL37 or ADAMTSL5 will receive SKYRIZI (Risakizumab) at Day 1, week 4, 16, 28, 40. LL37 and ADAMTSL5-specific T-cell responses will be evaluated at Day 0, week 16, week 28 and week 52. Each patient will be followed for 52 weeks.

Vitamin D (Vitamin D) deficiency is very common. We recently showed that 97% of 204 patients admitted to Truman Medical Center were Vitamin D deficient (\<30 ng/ml). However, the consequences of Vitamin D deficiency, particularly with respect to infection, are not well understood. It is known that production of cathelicidin, an important antimicrobial peptide, is critically dependent upon Vitamin D. It is also established that levels of cathelicidin correlate inversely with urinary tract infection risk. We hypothesize that restoration of Vitamin D levels to normal in patients undergoing major surgery will result in significant decreases in levels of perioperative infections due to restoration of normal levels of circulating Vitamin D, which in turn will elevate cathelicidin levels. As an initial test of this hypothesis, we propose a double-blind, prospective, randomized study of pre-operative Vitamin D supplementation. Fifty subjects undergoing surgery will receive daily Vitamin D3 (50,000 IU) for five days pre-operatively, with controls receiving placebo. Levels of Vitamin D, calcium, cathelicidin, and the pro-inflammatory protein resistin, will be monitored before Vitamin D supplementation (pre-operatively) and after Vitamin D supplementation (post-operative days 1 and 2). The effect of these changes should be to decrease the incidence of infectious complications. We expect to observe Vitamin D levels increase to normal, and cathelicidin levels become elevated. We expect to see increased levels of resistin in patients developing infections. This study will provide strong pilot evidence for future NIH funding. The long term goal in our research is to develop and implement effective, evidence-and mechanism-based interventions to improve outcomes for surgical and trauma patients. Of potential importance, findings from our own recent pilot studies have established that \> 95% of patients seen at Truman Medical Center (TMC) are seriously Vitamin D deficient with plasma levels significantly lower than normal. Our objective in this application, therefore, is to assess the short term therapeutic benefit of high dose Vitamin D in patients admitted to TMC for elective major abdominal surgery. We propose to measure plasma Vitamin D and Calcium levels before supplementation (pre-operatively), and after supplementation (post-operatively), and monitor the biomarker proteins cathelicidin and resistin at the same times. Data on Vitamin D levels will be used to assess direct biochemical effects. Measurement of cathelicidin levels will provide additional information. Since Vitamin D has been shown to induce increased expression of this antimicrobial protein. Monitoring of circulating levels of resistin provides a highly sensitive early measure of infection (unpublished observations). Calcium levels will also be monitored since there is a significant chance that pre-operative calcium levels will be low in some patients, and that supplementation with vitamin D may increase the calcium level. Measures of secondary clinical outcomes will include length of hospital stay and incidence of post-operation infection. Our central hypothesis is that, relative to patients receiving peri-operative standard of care, patients receiving 250,000 units of Vitamin D pre-operatively will manifest levels of Vitamin D to within the normal range and will have elevated levels of cathelicidin. We further hypothesize that patients receiving Vitamin D will have reduced incidence of infection, which will correlate with lower levels of resistin, and will exhibit trends toward shorter hospital stay. Our proposed specific aims are: Specific Aim #1: Determine biochemical consequences of Vitamin D supplementation in elective surgery patients We hypothesize that preoperative supplementation with high dose Vitamin D will result in levels of Vitamin D in treated patients within the normal range, corresponding with significant increases in plasma levels of cathelicidin, relative to control patients receiving standard of care. Specific Aim # 2: Evaluate clinical benefits of Vitamin D supplementation in post-elective surgery patients We postulate that patients given Vitamin D will trend toward lower rates of post-surgery infection, as evidenced by the absence of circulating resistin and decreased detection of pulmonary or wound-site infection, and will have shorter hospital stays relative to patients receiving standard of care. It is our expectation that, at the completion of this pilot study, we will have provided strong evidence that plasma levels of Vitamin D, as measured by 25-OHD, can be reproducibly raised to normal levels as measured in post-surgery patients and that the administered Vitamin D will have detectable biochemical benefits. We further expect that, while the power of the proposed study will not be sufficient for statistically valid results, there will be trends toward clinical benefits in Vitamin D treated patients. Collectively, these findings would provide strong evidence to support feasibility of an NIH-supported Phase I trial to assess Vitamin D benefits in surgery and/or trauma.

Adherence to a healthy dietary pattern is part of the self-care of patients with hypertension, and may contribute substantially to therapeutic target goals as well as to a better quality of life. However, not all nutritional recommendations aimed at these patients are easily applicable in clinical practice. The primary objective of the study is to evaluate the effectiveness of a nutritional strategy for blood pressure control in patients with hypertension users of a Public Health System after 6 months of follow-up. As secondary objectives, we will evaluate the impact of the proposed strategy on self-care and on the quality of life of the patients. In this multicenter open-label randomized trial, 408 patients ≥21 years old with hypertension, systolic blood pressure (SBP) ≥140mmHg at the moment of the screening and who have not received or received nutritional counseling for at least 06 months will be enrolled. Patients allocated to the control group will receive individualized dietary prescription according to the guidelines of the Brazilian Society of Cardiology. Nutritional counseling in the intervention group will be performed based on the quality of the diet, the Food Guide for the Brazilian Population and concepts of mindfulness and mindful eating; all dietary guidance will be based on feasible goals built together (patient and nutritionist), and no diet will be prescribed for intervention group. In both groups, patients will receive automatic monitors for residential self-monitoring blood pressure. On-site follow-up visits will be carried out at 30, 60, 90, and 180 days (final consultation). At 120 and 150 days, participants in the intervention group will receive motivational messages via e-mail or SMS (for these patients, consultation of 30 days will be a group meeting). Laboratory tests (lipid and glycemic profile, serum creatinine, serum sodium, urinary sodium, serum potassium, urinary potassium and albuminuria) will be performed at baseline and 180 days; anthropometric indexes and diastolic blood pressure (DBP) will be also evaluated.

The Mindful Parenting and Parent Training Study will be investigating the combination of Bögels and Restifo's (2014) Mindful Parenting Program and Chorpita and Weisz's (2009) Modular Approach to Therapy for Children with Anxiety, Depression, Trauma, or Conduct Problems (MATCH) Program, specifically the BPT module. The Mindful Parenting Program is an adaptation for parents of the Mindfulness-Based Cognitive Therapy, and the Mindfulness-Based Stress Reduction program; the program will consist of 7-weekly 2.5-hour parent group sessions. Following the completion of the Mindful Parenting group sessions, half of the participants will be randomly selected to receive individually-implemented MATCH BPT sessions, which will consist of 8-12 weekly (depending on how long it takes for individual parents and their assigned trainer to get through the material), 1.5-hour sessions. The other half of families will have the opportunity to also receive the MATCH BPT program following the completion of data collection. Both evaluation and treatment services will be offered at no cost to study participants. Parents, children, and teachers will also be offered monetary incentive to thank them for their time and effort completing study related assessments throughout the course of the study to determine if the combination of the Mindful Parenting Program with BPT improves functioning in children with disruptive behavioral problems, as well as the parent-child relationship and the parent's acquisition and enactment of the skills they learn in BPT.

Studies have shown that people with chronic obstructive pulmonary disease (COPD) have worse symptoms after breathing polluted air. People with COPD also often need to go to the hospital if they get a virus or other bug. One of the main drugs taken for COPD treatment (inhaled corticosteroid) may change COPD patients' lungs in ways that make it harder to deal with bugs, especially if they breathe in polluted air. If so, this could cause more frequent hospital visits. On the other hand, the same drug (inhaled corticosteroid) helps some people control symptoms, and may help them avoid hospital visits. The APEL investigators are conducting this study (APIC) to understand if this drug (inhaled corticosteroid), in combination with polluted air, will change the lungs of those with COPD in ways that make it more likely to catch bugs or have other problems. APIC will involve 48 volunteer participants (24 of each biological sex assigned at birth) with mild-to-moderate COPD where the researchers will look at what (if any) are the differences between breathing in fresh air (filtered air - FA) or polluted air (diesel exhaust - DE) while taking the drug (Inhaled corticosteroid - ICS) or not (no ICS), both in combination with two standard COPD medicines that make it easier to breath (a long-acting beta-agonist and a long-acting muscarinic antagonist). The participant will take an inhaled medication daily throughout the study. This study will use a controlled amount of diesel exhaust to model traffic-related air pollution (TRAP), a commonly encountered form of polluted air. Each participant will act as their own control, as they will experience all four combinations: 1) FA-ICS, 2) FA-no ICS, 3) DE-ICS, and 4) DE-no ICS. These combinations will be randomized in what researchers call a double-blinded crossover study, so that every participant will get these combinations in a different order. However, only the engineer on the team will be allowed to know which participant gets what. Blinding will prevent everyone else, including the participant, from being biased against the conditions and affecting outcomes based on this perception. The study will span over five months (approximately 121 days of active commitment), which includes ten in-person visits to a research office at the Vancouver General Hospital, for a total of approximately 40 hours. While the participant is on-site, the investigators will supervise a series of questionnaires, sample collection (blood, urine, bronchoscopy lung samples), and lung function tests. The investigators will evaluate multiple endpoints as detailed in the Outcome Measures section. For each applicable endpoint, the investigators will evaluate stratified analyses and effect modification by biological sex, participant age, gene score, and microbiomes. The investigators do not expect that the participant's responses to either the corticosteroid or diesel exhaust will be noticeable to them. Any responses that may occur will probably only be detectable through careful examination of their cells and tissues (e.g., blood, urine, bronchial samples). However, understanding the subtle changes that may occur could help reduce or prevent health problems associated with TRAP exposure in the future.