Active clinical trials for "Autoimmune Diseases"

The main study objective is to determine whether 24/7 automated closed-loop glucose control combined with low glucose feature will improve glucose control as measured by HbA1c. This is an open-label, multi-centre, multi-national, single-period, randomised, parallel group design study, involving a 6 month period of home study during which day and night glucose levels will be controlled either by a closed-loop system combined with low glucose feature (intervention group) or by insulin pump therapy alone (control group). It is expected that a total of up to 150 subjects (aiming for 130 randomised subjects) with type 1 diabetes will be recruited through paediatric outpatient diabetes clinics of the investigation centres. Participants will all be on subcutaneous insulin pump therapy. Subjects in the intervention group will have proven competencies both in the use of the study insulin pump and the study continuous glucose monitoring (CGM) device, and will receive appropriate training in the safe use of closed-loop insulin delivery system and low glucose feature. All subjects will have regular contact with the study team during the home study phase including 24/7 telephone support. The primary outcome is between group differences in HbA1c levels at 6 months post study arm initiation. Secondary outcomes are the time spent in the glucose target (3.9 to 10.0mmol/l; 70 to 180mg/dl), time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics. Safety evaluation comprises assessment of the frequency of severe hypoglycaemic episodes and diabetic ketoacidosis (DKA).

This study will examine whether the drug pyrimethamine can shrink lymph nodes and spleen in patients with autoimmune lymphoproliferative syndrome (ALPS). In this disease, lymphocytes (white blood cells) do not die as they normally would. As a result, patients have enlarged lymph glands, spleen, or liver, and other problems that may involve blood cell counts and autoimmune disease (overactivity of the immune system). Pyrimethamine is an orally administered antibiotic that has been used to treat or prevent malaria and toxoplasma, and may be effective in shrinking lymph nodes and spleen. Patients with ALPS who are between 2 and 70 years of age and have had lymph gland enlargement for at least 1 year may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, and possibly a bone marrow test. Females of reproductive age will be screened with a urine pregnancy test. Women who are capable of becoming pregnant must use an effective method of birth control during the entire study period, because, taken during early months of pregnancy, pyrimethamine can cause birth defects in the fetus. Women who are pregnant or nursing are excluded from the study. Participants will undergo the following tests and procedures: CT scan: For this test, the patient lies still in the CT scanner while images are taken of the neck, chest, and stomach area. A contrast dye is injected into a vein to brighten the CT images. Very young children will be evaluated on a case by case basis to determine whether a CT scan will be performed. Bone marrow biopsy: Participants undergo this test to rule out underlying bone marrow disease if they have not had a bone marrow test done in the last six months prior to enrolling in pyrimethamine study, as pyrimethamine can affect bone marrow function. Under local anesthesia, a needle is inserted into the back part of the hipbone and a small amount of marrow is removed. (Children are sedated for this test.) Leukapheresis: This is a procedure for collecting a small proportion of circulating white blood cells while conserving the majority of blood cells. Specifically, blood is drawn from a needle placed in an arm vein and is directed into a cell separator machine, which separates the blood cells by spinning. A small proportion of circulating white cells are removed, and the red cells, platelets, plasma and majority of white cells are returned to the patient's blood circulation. Only patients who are 7 years of age or older and weigh at least 55 pounds undergo this procedure. Other participants who choose not to have apheresis will have about 3 tablespoons of blood drawn instead. Pyrimethamine administration: When the above tests are completed, participants begin taking pyrimethamine. The dose is determined according to the individual's weight and is gradually increased during the study period. Patients take the drug twice a week for a total of 12 weeks. Blood tests: Blood samples are collected during weeks 2, 4, 6, 8, and 10 after beginning treatment, and 2 weeks after the last dose of pyrimethamine. The purpose of these blood tests is to check for possible drug-related side effects. Patients who develop a skin rash, mouth sores or other side effects may have one or more doses of the treatment drug withheld. When indicated, the patient will be directed to stop taking the study drug. If needed, drug side effects will be treated with a vitamin supplement, folinic acid, taken by mouth, 3 times weekly. Evaluations at the NIH Clinical Center will comprise of a pretreatment visit, one end of treatment visit at the end of 12 weeks and an optional post-treatment visit 3months after stopping pyrimethamine therapy. Patients who respond well to treatment may be asked to return to NIH for additional visits at 3, 6, and 12 months after the treatment has ended for repeat evaluations. If their lymph glands or spleen become much larger after stopping pyrimethamine, they will be offered treatment for another 12 weeks. If they respond to the second course of treatment, they will return to NIH again after 3, 6, and 12 months. If the symptoms return again, patients will be asked to resume treatment for an additional 6 months or more. They will have blood drawn periodically by their private physician and will return to NIH for evaluation every 12 weeks.

This study will evaluate the safety and effectiveness of an antibiotic called Fansidar on autoimmune lymphoproliferative syndrome (ALPS). Patients with ALPS have enlarged lymph glands, spleen and/or liver, abnormal blood cell counts and overactive immune function. Current treatments are aimed at suppressing the immune system and improving symptoms, such as anemia (low red blood cell count) and low white blood cell and platelet counts. These treatments, however, are only partially effective and may have complications. Fansidar is a combination of two drugs, sulfadoxine and pyrimethamine, that is used to treat or prevent parasitic infections such as malaria. Recently a child with ALPS who was treated with Fansidar for a different illness had a marked shrinkage of the lymph organs. This study will examine whether Fansidar can shrink the lymph glands or spleen in patients with ALPS. Patients with ALPS between the ages of 4 and 70 years who have had lymph gland enlargement for at least 1 year and are not allergic to sulfa drugs may be eligible for this study. Candidates will be screened with a medical history and physical examination and blood tests. Females of reproductive age will have a urine pregnancy test. Participants will be evaluated at the NIH Clinical Center in Bethesda, MD, with blood tests and a computed tomography (CT) scan of the lymph nodes. For the CT scan, the patient lies on a table during an X-ray scan of the neck, part of the chest, and, if the spleen has not been removed, the stomach area. When these baseline tests are completed, patients will be given Fansidar pills to take once a week for 12 weeks. The dosage will be increased after 2 weeks and again after 4 weeks. At 2, 4, 6, 8 and 10 weeks after starting the treatment and 2 weeks after the last dose, patients will have blood drawn to check for possible side effects of therapy. Women will have a repeat urine pregnancy test at week 6 of treatment. Within a week before completing treatment or after completing treatment, patients will return to NIH for a history, physical examination, blood tests and CT scan. Patients who responded well to treatment will be offered to return to NIH again 3, 6 and 12 months later to repeat the evaluations. If ALPS symptoms recur during this time, patients will be offered another 12-week course of Fansidar and the procedure, including the 3, 6 and 12-month evaluations will be repeated again. If symptoms recur again, patients will be asked to resume Fansidar for 6 months or longer, with doses adjusted as needed. During this time, patients will be seen at NIH every 12 weeks for evaluation and blood will be drawn by the patient's private physician every 6 weeks or 2 and 4 weeks after the dose is increased to check for side effects.

The study plans to enroll approximately 12 subjects. The main objective of the study is to assess the safety, tolerability and pharmacokinetics (PK) of the three times a day (TID), dosing of GSK2982772, in Japanese healthy male subjects. The study will comprise of four study periods each at least 7 days in duration with subjects in-house for 4 nights (through 72 hrs after the first dose). During each treatment period (TP), subjects will be admitted to the unit the day before dosing and will be discharged after completion of the 72 hours post-dose assessments. There will be a washout of atleast 7-days between the TP doses for each individual, post which there will be 7-days follow-up. The dose range proposed in this study is based on a low starting dose, which will be escalated to the highest dose that is intended for the Phase 2b dose range study. The decision to proceed to the next dose-level, of GSK2982772 within the study will be made by principal investigator and GSK Medical Monitor per each dosing periods. The study duration is approximately 22 weeks.

Tolerogenic dendritic cell (tDC)-based clinical trials for the treatment of autoimmune diseases are now a reality. Clinical trials are currently exploring the effectiveness of tDC to treat of type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis and Crohn's disease. The general objective of this study is to evaluate the safety and tolerability of a single intra-articular injection (into the knee joint) of autologous monocyte-derived dendritic cells generated in the presence of interferon-alpha (IFN-α)/granulocyte-macrophage colony-stimulating factor (GM-CSF) and tolerized with Dexamethasone in rheumatoid arthritis (RA) patients.

The objective of DIAGNODE-2 is to evaluate the efficacy of Diamyd compared to Placebo, upon administration directly into a lymph node in combination with an oral vitamin D/Placebo regimen, in terms of preserving endogenous insulin secretion as measured by C-peptide.

Hashimoto's thyroiditis (HT) is the most commonly observed inflammatory and autoimmune disease of the thyroid gland. Many genetic and environmental factors play a role in the pathogenesis of the disease, including iodine exposure, drugs, chemicals, toxins, infections and smoking. In recent years, the relationship between oxidative stress level and thyroid autoantibodies in HT has attracted increasing attention of researchers. In the studies, it has been reported that oxidative stress levels may increase due to chronic inflammation, insufficient thyroid hormone levels, excessive autoimmune response and excessive iodine intake. Data from clinical studies clearly show that the balance between oxidants and antioxidants shifts towards the oxidative side in patients with autoimmune thyroiditis, suggesting that oxidative stress may be a key event in the pathophysiology of the disease, independent of thyroid function. Recent evidence has suggested that low-level laser therapy (LLLT) can improve thyroid function and reduce levels of thyroid peroxidase antibodies (TPOAb) in patients with hypothyroidism caused by chronic autoimmune thyroiditis. In the literature, data examining the effects of LLLT on oxidative stress level and quality of life in patients with HT is limited. As far as we know, it will be the first study examining the effect of LLLT on oxidative stress, fatigue and quality of life in cases diagnosed with HT. The aim of the study is to examine the effects of LT4 treatment combined with LLLT on thyroid autoimmunity, oxidative stress, fatigue and quality of life in patients with Hashimoto's diagnosis.

Together with Crohn's disease (CD), ulcerative colitis (UC) is one of the major forms of inflammatory bowel diseases (IBD).Currently, no curative therapy is available, since the pathophysiology of this disease is incompletely understood (1-3) and clinical practice demonstrates that current therapies induce remission in subgroups of patients only. Scientific evidence suggests that colitogenic immune responses can be controlled by increasing the number of circulating regulatory T cells (Treg) (4). The production of large numbers of autologous Treg is possible by isolation of CD25+ cells from the whole blood of a patient and subsequent ex vivo expansion in the presence of the immunomodulatory drug rapamycin, Interleukin-2 (IL-2) and CD3/CD28 expander beads (5). ER-TREG 01 is a single-center, open-label, fast-track phase I dose-escalation study designed to assess the safety profile and maximal tolerated dose (MTD) of a single infusion of ex vivo expanded autologous Treg in patients with active ulcerative colitis.

Axial spondyloarthritis (axSpA) is a chronic inflammatory immune disorder with a global prevalence that ranges from 20 to 160 cases per 10000 individuals. axSpA has two forms of clinical presentation (radiographic and non-radiographic) based on the presence or absence of radiographic sacroiliitis. This condition mostly affects the vertebral spine, and is characterized by joint pain and stiffness, fatigue, and restricted function, which leads to a substantial physical, psychological, and socioeconomic burden. The clinical management of axSpA needs to combine pharmacological and non-pharmacological approaches to reduce inflammation and improve health-related quality of life. The aim of the study will be to determine if a 12-week probiotic supplementation will be more effective than an online-delivered strength training program at improving functional capacity in adults with non-radiographic axSpA. As a secondary aim, we will compare the impact of both interventions on disease activity, spinal mobility, quality of life and biochemical measures. This will be the first randomized controlled trial where probiotics are compared with an active intervention.

GSK2982772 is a first-in-class, highly selective, receptor-interacting protein-1 (RIP1) kinase inhibitor being developed for the treatment of inflammatory bowel disease, plaque psoriasis (PsO), rheumatoid arthritis (RA) and other disease conditions. PK data from the first time in human (FTIH) study for GSK2982772 showed that the half life of GSK2982772 was short (approximately 2 to 3 hours). A once daily (QD) formulation would be more convenient from a subject perspective and could offer the advantage of providing a flatter GSK2982772 concentration time profile. Following completion of Parts A and B, it was determined that the slowest minitab formulation provided a PK profile suitable for QD dosing but this formulation was susceptible to a food effect. This study will evaluate the pharmacokinetics of GSK2982772 following administration of different minitab MR formulations in a capsule relative to an IR reference tablet formulation, the pharmacokinetics of selected MR formulation in capsule following repeat doses for 3 days and to compare the pharmacokinetics of GSK2982772 following administration of MR tablet formulations in the fed and fasted state relative to an IR tablet formulation. The study is divided into three parts: Part A will be a non-randomized 6 periods, sequential, 6-way fixed sequence design in which up to 4 MR minitab formulations in a capsule will be evaluated. Periods 1, 2, and 3 will evaluate a slow MR release duration (nominally 24 hours), a fast MR release duration (nominally 10 hours), and IR tablet respectively. Periods 4, 5 and 6 will have flexible dose regimen and it will depend on the outcomes of Period 1 to 3. Subjects will be admitted to the clinic the previous day before dosing. Each in-patient period will consist of 3 days and 2 nights followed by a minimum washout period of 7 days between doses, for both Part A and C. In Part A and C, 16 healthy subjects will be enrolled such that at least 12 evaluable subjects complete the study. Part B will be an open-label, repeat dose study in which the selected MR minitab formulation in capsule will be evaluated. Each in-patient period will consist of 5 days and 4 nights. There will be a minimum of 7 days washout period between the last morning dose of one period and the first dose of the next period. In Part B, 10 healthy subjects will be enrolled such that at least 6 evaluable subjects complete the study. Part C of the study will be a non-randomised 6 period, sequential, fixed sequence crossover design in which MR tablet formulations will be evaluated. Periods 1 and 2 will evaluate single dose administration of a 240 milligram (mg) MR tablet and the 240 mg IR tablet (reference), respectively. Periods 3, 4, 5 and 6 will be flexible and the dosing regimen will be dependent on the outcome of Periods 1 and 2.