Research Studies

This study in healthy men and women looks at the injection site experience of the DV3396 pen to that of the PDS290 pens when both pens are used to deliver 0.25 mg semaglutide subcutaneously (s.c., under the skin). Participants will receive 2 single doses of semaglutide 0.25 mg on 1 day. The 2 injections will be given at least 30 minutes apart, one in each side of the stomach. Participants will be in the clinic research center for 1 day. A follow-up phone call will take place between 4 and 5 weeks after the injections were given.

This study looks at how participants with type 2 diabetes take Ozempic® and if the Ozempic® app helps participants to stay on this treatment. Participants will already be prescribed with Ozempic® by the study doctor. Participants may be asked to use a device called Mallya®, which participants must attach to their Ozempic® injection pen. Participants might also be asked to install an Ozempic® app on their mobile phone which supports the participants in the use of Ozempic®. At the beginning and at the end of this study, the participants will have to fill out some questionnaires about their diabetes treatment. Participants may also be chosen to participate in a voluntary non-mandatory interview after the study has ended. The total duration of study is approximately 10 months.

Post-operative administration of ipamorelin is expected to reduce time to recovery of Gastrointestinal (GI) function in patients who have undergone partial small and/or large bowel resection.

The purpose of this study is to determine if ipamorelin is safe and effective in the management of post-operative ileus. The safety and efficacy of ipamorelin in the management of post-operative ileus

Background: People who have had a traumatic brain injury (TBI) often have trouble sleeping. TBI may also alter hormones, which can cause poor sleep. Researchers believe that a form of growth hormone releasing hormone (GHRH) might improve sleep in service members and veterans who have had a TBI. Objective: To see if GHRH can improve sleep in people who have had a TBI. Eligibility: Active duty service members or veterans (active duty in the past 10 years) ages 18-45 who have had a TBI in the past 6 months to 10 years. Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Getting ACTH (a hormone) through an intravenous catheter (thin plastic tube) Interview about their mood and alcohol and drug use Questionnaires about their TBI, mood, and sleep Participants will have 2 overnight study visits a couple weeks apart. These will include: Physical exam Urine sample Two intravenous catheters placed. Blood samples will be taken throughout the night. Two shots under the skin of the belly. The shots will be GHRH on one visit and placebo on the other. Spending the night in the sleep lab. Their brain waves will be recorded with electrodes placed on the scalp. A questionnaire in the morning about their sleep Participants will be called a few days after each overnight visit. They will be asked about how they are feeling and to rate their sleep. Objective: Traumatic brain injury (TBI) is the hallmark injury of deployment in Iraq and Afghanistan. Up to one-third of service members who sustain a TBI are diagnosed with a sleep disorder; insomnia being one of the most common. Currently, over half of TBI-associated insomnia cases remain untreated due to poor efficacy of available pharmacologic agents. Neuroendocrine dysfunction is an important mechanism linking TBI and disordered sleep, thus pharmacological agents that address this dysfunction may be effective in treating TBI-related insomnia. The neuroendocrine system is essential for regulating sleep and circadian function. Decreased neuroendocrine function, including the hypothalamus and the somatotrophic cells of the anterior pituitary, which regulate growth hormone secretion, likely contributes to insomnia. This assertion is supported by previous studies that demonstrated the sleep-promoting effects of growth hormone releasing hormone (GHRH) administration in healthy controls, the elderly, and participants with depression. Therefore, we propose that administration of GHRH will address the underlying mechanisms of insomnia in service members and veterans who sustained a TBI, and provide a pharmacological agent more robust than currently available treatments. Study population: This study will recruit 50 active duty service members and veterans with a documented TBI to participate in one of two study groups. The insomnia group (n=25) will include participants that have a current clinical diagnosis of insomnia without obstructive sleep apnea. The no-insomnia group (n=25) will include participants with no current clinical diagnosis of insomnia or obstructive sleep apnea. Withdrawals/dropouts will be replaced to obtain 20 participants per group who complete the study. Design: A double-blind, randomized, crossover design will be used to examine the impact of tesamorelin (GHRH (1-44) analog) or placebo on total non-rapid eye movement (NREM) time evaluated during two polysomnography visits, scheduled 1-3 weeks apart. Serial blood draws will be obtained during the polysomnography to examine endocrine function and neuropeptide release. Outcome measures: The primary outcome is change in NREM time following tesamorelin administration compared to placebo. The secondary outcomes are (1) within and between group differences in plasma concentration levels of neuroendocrine proteins following tesamorelin administration compared to placebo and (2) within and between group differences in urinary concentration levels of growth hormone following tesamorelin administration compared to placebo.

Tuberculosis is a disease caused by a bacterium (a germ) that can cause illness in any organ of the body, but most frequently causes disease of the lungs. TB is short for tuberculosis. Treating TB requires several months (usually 6 months) of treatment, with the first 2 months being intensive treatment with usually four medicines. Treatment is needed to keep the infection from getting worse and to prevent death from TB. Vitamin D is a hormone present in the human body to manage levels of some essential electrolytes such as calcium and phosphate. Vitamin D is important for bone formation and prevention of bone breakdown (osteoporosis) as the investigators age. There is also new evidence that links vitamin D to function of our immune system as well. Even though our bodies can make vitamin D and can also obtain vitamin D from our diet, most adults, especially patients with tuberculosis have low vitamin D levels (are vitamin D deficient) that need to be corrected. Full correction of low vitamin D levels requires 6 weeks or more of weekly vitamin D supplements. There are several benefits to correcting vitamin D deficiency (better bone health, better balance of calcium and phosphate), but it is not known whether correcting vitamin D deficiency will lead to a better immune response to tuberculosis. Preliminary data does suggest that vitamin D increases the levels of an antimicrobial molecule (cathelicidin LL-37) in the body, possibly leading to better immunity against tuberculosis. The primary objective of this pilot study is to assess the relationship of vitamin D levels in patients with active pulmonary tuberculosis to levels of LL-37 cathelicidin in sputum and whole blood. The results of this study are needed in preparation for larger studies that will evaluate the role of vitamin D supplementation as adjunctive therapy to standard medical treatment for tuberculosis. 1.0 Introduction and Background Tuberculosis remains an enormous public health problem and a major cause of morbidity and mortality throughout the world. The WHO estimates that 8.8 million new cases of tuberculosis occurred worldwide in 2005, along with 1.6 million TB related deaths. New challenges in TB control include the HIV epidemic, as well as the emergence of multidrug resistant (MDR) and extremely drug resistant (XDR) strains of tuberculosis which are associated with high morbidity and mortality. While cure rates for drug susceptible TB can reach the \>90% range given the appropriate infrastructure to diagnose and treat patients, cure rates for MDR-TB are much lower and, at best, approach 60% according to the latest estimates by WHO. In many parts of the world, second line drugs to treat MDR-TB are not available. Not only is there an urgent need for novel TB treatment regimens, but adjunctive therapeutic modalities need to be explored with the goal of maximizing clinical response for both patients with drug susceptible and drug resistant disease. The use of vitamin D as primary or adjunctive TB therapy has a long history. Therapeutic doses of oral vitamin D supplementation for TB treatment were first pioneered in the 1950's by Jacques Charpy, who noted excellent results in cutaneous TB disease. Subsequently, vitamin D has been used as both primary and adjunctive therapy in pulmonary tuberculosis, but this practice fell out of favor as effective antimycobacterial chemotherapy became widely available in the latter half of the twentieth century. More recently, however, there has been a resurgence of interest in vitamin D as an effective adjunctive therapy in tuberculosis. Recent reports indicate that vitamin D may have a pronounced immunomodulatory role in the pathogenesis of tuberculosis within the human host. It is well known that areas of granulomatous inflammation in TB are sites of increased vitamin D production stemming from activated macrophages and Th1 lymphocytes within the granuloma Recently, the immunomodulatory function of increased vitamin D levels at sites of TB involvement has been demonstrated, in that 1,25(OH)2D, the active metabolite form of vitamin D, has been found to induce antimycobacterial activity in vitro in both monocytes and macrophages. One proposed pathway for this observed immunomodulatory effect of vitamin D in TB infection involves the toll-like receptor (TLR) signaling pathways of the innate immune system. Liu et al demonstrated that macrophage TLR binding of M. tuberculosis antigen upregulates the expression of cellular 1 hydroxylase, resulting in higher levels of active 1, 25(OH)2D. It was also shown that 1, 25(OH)2D in turn binds the nuclear vitamin D receptor (VDR), which activates a downstream signaling cascade resulting in the upregulation of several aspects of the innate immune response, including the induction of a newly described anti-microbial peptide LL-37, a cathelicidin. Cathelicidins, in addition to their broad spectrum antimicrobial activity, also possess chemotactic properties for neutrophils, monocytes and T cells, among other functions within the immune system. While this mechanism of action for vitamin D was demonstrated in vitro, little clinical work has been done to validate this piece of knowledge in clinical practice and in the care of TB patients. As proxy for in vivo studies, subsequent experiments by Liu et al evaluated induction of cathelicidin by TLR activation of macrophages in sera from African American and Caucasian subjects. These experiments demonstrated failure to induce detectable levels of cathelicidin mRNA in samples from African American patients, who are known to be significantly more vitamin D deficient than Caucasians due to difference in vitamin D production in the skin. The difference in cathelicidin mRNA levels was corrected upon supplementation of deficient sera to therapeutic levels of 25(OH)D3 prior to TLR stimulation. Given the preliminary results of these in vitro studies, we propose a clinical pilot investigation of the relationship between vitamin D levels and cathelicidin production in TB patients. It is well known that the majority of TB patients are deficient in vitamin D, but it is unknown whether the deficiency has functional consequences for treatment response and relapse rates. While recent in vitro data suggests that vitamin D supplementation of recent TB contacts does improve their immune response to Mycobacterium tuberculosis as measured in whole blood assays, clinical trials of vitamin D supplementation in latent or active TB disease have not been undertaken. In preparation for larger trials that would be needed to address this clinical question, we propose that the clinical relationship between physiologic levels of vitamin D supplementation and effect on cathelicidin production within the host needs to be studied, given recent suggestions from in vitro studies that ability to generate adequate cathelicidin levels may have an impact on quality and effectiveness of host immune defense against M. tuberculosis. 2.0 Objectives 2.1 Overall Objective The primary objective of this pilot study is to assess the relationship of 25-hydroxy vitamin D levels in patients with active pulmonary tuberculosis to levels of LL-37/cathelicidin in sputum, saliva, and whole blood.

The purpose of this study is to determine whether stereotactic body radiotherapy (SBRT) combined with recombined human granulocyte-macrophage colony stimulating factor(rhGM-CSF) and Thymosin Alpha 1 is safe, effective in the treatment of stage IV NSCLC patients who failed in second-line chemotherapy. Metastasis lesion of stage IV NSCLC will be treated with a SBRT of 50Gy/4-10F from day 1 to day 14 in one cycle. Subcutaneous injection of human recombined granulocyte-macrophage colony stimulating factor (125ug/m² per day) will be executed from day 1 to day 14 in this cycle. Another metastasis lesion will be treated likewise concurrently with rhGM-CSF in a consecutive cycle.Thymosin Alpha 1(1.6mg Biw) will be Subcutaneous injection from the fist week to the 12th weeks, Efficacy evaluation, especially abscopal effect evaluation, will be conducted at the end of therapy and every month after that. Adverse events will be recorded according to NCI-CTC version 4.03.

The purpose of this study is to assess the safety,tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of an extended dosing regimen of ITF2984: part A, designed as double-blind, placebo-controlled, randomized, tested an extended dosing regimen, i.e. 14 consecutive dosing days and higher doses, i.e. up to 6000 mcg/day and in part B, open label, continuous subcutaneous infusion for 7 days were tested as ascending doses of ITF2984 up to 9000 mcg/day of ITF2984. This was a two part Phase I repeated incremental doses study in male healthy volunteers. The study was conducted in two parts. A total of 36 subjects was planned to be enrolled in Part A and 36 subjects in Part B. Part A was performed according to a double blind, randomized, placebo controlled design and included three sequential dose groups of repeat doses. Each group enrolled 12 subjects on ITF2984 or placebo (ratio 9 active: 3 placebo) and received ITF2984 s.c. or placebo twice daily for 14 days. For all three groups the last dose was planned to be the first dose on Day 14. The study started with the Group 1 2000mcg s.c. b.i.d., Group 2 received 3000mcg b.i.d. after an interim review of the safety and PK data of the 2000mcg dose level. Group 3 received 100mcg s.c. to gather data to complete the PK/PD profile of ITF2984. Subjects were screened up to 28 days before dosing with ITF2984/placebo that took place on Days 1-14. For all Groups, on day -1 and day 13 subjects received the exogenous tests administration (GHRH, Arginin and TRH) 30 minutes after the first morning administration of ITF2984/placebo. Part B was open label, and planned for six sequential dose groups of 6 subjects each. In each group subjects received ITF2984 continuous subcutaneous infusion for 7 consecutive days. The dose was escalated, from the starting dose of 900 mcg, by a maximum of three fold or more cautiously, if deemed necessary. The decision to test higher dose levels was based on review of safety and PK data from the previous dose level(s). After a 28 day screening period, subjects were admitted to the clinical unit on the evening of day -2. ITF2984 continuous infusion planned from day 1 to day 8 in the morning. On day -1 (the day prior to the start of infusion) subjects received the exogenous/challenge test administrations (GH-RH+Arginina and TRH). On day 7 the challenge tests were repeated.

Primary biliary cholangitis (PBC) is a rare chronic, progressive, cholestatic liver disease that leads to cirrhosis and its life-threatening complications if undertreated. Ursodeoxycholic acid (UDCA) is the standard-of-care therapy for PBC. However, patients with an inadequate biochemical response to UDCA according to the Paris-2 criteria are still at high-risk of poor clinical outcome. In this situation of biochemical resistance to UDCA, bezafibrate 400 mg/d given in association with UDCA has been shown to improve the symptoms, biochemical response (BEZURSO study), histologic features, and possibly long-term clinical outcome. However, it has been shown that even patients with an adequate response to UDCA but persistent elevation in biochemical markers of cholestasis or liver inflammation, including alkaline phosphatases (ALP), gamma-glutamyl transpeptidase (GGT), transaminases, or total bilirubin (i.e., non-optimal biochemical response) have still an increased risk of death or liver transplantation in the long term, thus defining the complete normalization of these markers as the new clinically-relevant target for PBC treatment. In parallel to these findings, bezafibrate 400 mg/d as a second-line therapy for PBC could be associated with potentially dose-related, muscle, kidney, or liver toxic effects, and whether bezafibrate 200 mg/d could have a better benefit/risk ratio in this disease-setting remains to be determined. Therefore, our aim is to evaluate the efficacy and safety of bezafibrate 400 mg and bezafibrate 200 mg as adjunctive treatments in PBC patients with non-optimal biochemical response to UDCA. The study is a phase-3 multicenter, randomized, parallel-group (1:1:1), placebo-controlled trial with a 12-month, double-blind, placebo-free extension phase. It evaluates the efficacy and safety of bezafibrate 400 mg and bezafibrate 200 mg as adjunctive treatments in patients with PBC with an non-optimal biochemical response to UDCA. Treatments groups : Arm 1: Bezafibrate 400 mg and Placebo of Bezafibrate 200 mg until 96 weeks in double blind. Arm 2: Bezafibrate 200 mg and Placebo of Bezafibrate 400 mg until 96 weeks in double blind. Arm 3: Placebo of Bezafibrate 400 mg and Placebo of Bezafibrate 200 mg until 48 weeks in double blind. Then follow-up extension phase of bezafibrate 400 mg or bezafibrate 200 mg (second randomization) until 48 weeks in double blind. Assessement: Study visits at Inclusion, Randomisation (M0) and then every 3 months until W48 and extension until W96. In accordance with routine care, an additional follow-up is added between 108 and 120 weeks 32 sites within the French network of reference and competence centres for rare liver diseases FILFOIE will participate. No interim analysis planned. Analysis will be performed at the end of the study after data reviewed and data base locked according to the intent to treat principle.

OBJECTIVES: I. Determine whether release of endogenous growth hormone (GH)-releasing hormone is involved in GH responses to clonidine, pyridostigmine, levodopa, arginine, GH-releasing peptide, insulin-induced hypoglycemia, and exercise in patients with acromegaly. II. Determine whether endogenous GH-releasing hormone influences the maintenance of GH hypersecretion. PROTOCOL OUTLINE: Growth hormone-releasing hormone antagonist (GHRH-A) is administered to volunteers and followed with 1 of these challenges: insulin, clonidine, pyridostigmine, arginine, levodopa, growth hormone-releasing peptide, or exercise. Tests are repeated with normal saline as the control; the order of administration (control vs. pharmacologic stimulation) is randomly assigned. Patients receive GHRH-A (dose determined in volunteer study), thyrotropin-releasing hormone, and growth-releasing hormone. All stimulation tests follow an overnight fast.