View clinical trials related to Scleroderma, Diffuse.
Filter by:This study investigates the efficacy and safety of STI571 for the treatment of fibrosis in participants with systemic sclerosis. Other purposes of the study were to investigate whether STI571 is effective in improving lung functions and other test results called biomarkers. Whether STI571 is well-absorbed in systemic sclerosis participants' gut was also investigated by testing the drug level in the blood (pharmacokinetics).
Transforming growth factor-beta 1 (TGF-β1) is consistently over expressed in most fibrotic diseases and displays a variety of profibrotic effects in fibroblasts. Activation of TGF-β receptors induces the activation of several kinase signalling cascades leading to the phosphorylation of SMAD proteins as well as to the activation of SMAD-independent kinases that collectively activate ECM synthesis and fibroblast growth and differentiation into myofibroblasts. TGF-β1 is one of the main mediators in the fibrotic process, associated to both scarring and a long list of pathologies related to chronic inflammation and which affect all type of organs and tissues. An increase in TGF-β1 mRNA and protein levels has been described in these processes. Peptide 144 (P144) is the acetic salt of a 14mer peptide from human TGF-β1 type III receptor (betaglycan). P144 TGF-β1-inhibitor has been specifically designed to block the interaction between TGF-β1 and TGF-β1 type III receptor, thus blocking its biological effects. P144 has shown significant antifibrotic activity in mice receiving repeated subcutaneous injections of bleomycin, a widely accepted animal model of human scleroderma, and could contribute to the development. The purpose of this study is to asses the efficacy and safety of topical application of P144 in the treatment of skin fibrosis in patients with systemic sclerosis.
To determine sleep disturbance, pulmonary function test, 6 minute walk, echocardiogram abnormality, arterial blood gas, ventilation/perfusion scan of the chest in Scleroderma patient with Pulmonary Hypertension.
The purpose of this study is to assess the safety and tolerability of imatinib mesylate (Gleevec) in patients with systemic sclerosis (scleroderma). Gleevec is a medication already FDA approved for the treatment of chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GIST), dermatofibrosarcoma protuberans tumors, Philadelphia chromosome-positive acute lymphoblastic leukemia, hypereosinophilic syndrome, and aggressive systemic mastocytosis. In-vitro studies have suggested that imatinib may inhibit collagen production by scleroderma fibroblasts, and in mouse models of fibrosis imatinib has been shown to decrease skin thickness. This is a Phase IIa, single center, prospective open label clinical trial of Gleevec in patients with systemic sclerosis. All patients will be treated with active drug for 12 months. The primary objective of this study will be to determine the safety and tolerability of Gleevec in patients with systemic sclerosis, but important secondary outcomes of relevance will be improvement in disease status as defined by skin scores and indices of pulmonary function. Patients who complete the initial phase (described above) of the study will be eligible to participate in an extension phase. The purpose of the extension phase of the study is to give patients who participated in the phase IIa clinical trial of Gleevec at the Hospital for Special Surgery the opportunity to continue Gleevec treatment if both the treating physicians and the patient are in agreement that Gleevec had acceptable safety and tolerability, as well as possible efficacy during the initial year of therapy.
To explore the hypothesis that leg ulcers are associated with hypercoagulable states, the CLUE study will evaluate patients with connective tissue disease associated leg ulcers, to identify risk factors (especially hypercoagulability and immunologic characteristics), characterize pathogenesis, predict response to therapy, and assess the impact of lower extremity ulcers on quality of life.
It is difficult to predict how a women with an autoimmune disease will do during pregnancy. Some women will improve, others will worsen. Some pregnancies progress normally and others become very complicated. The Duke Autoimmunity in Pregnancy (DAP) Registry will enroll women with autoimmune diseases, such as lupus, rheumatoid arthritis, scleroderma, and Sjogren's syndrome who wish to become, or already are, pregnant. We will follow these women throughout pregnancy to better understand how their autoimmune disease affects their pregnancy, and vice versa.
The purpose of this study is to assess the safety and tolerability of imatinib (gleevec) in subjects who have systemic sclerosis. Imatinib has been approved by the FDA for the treatment of newly diagnosed adult patients with CML (newly diagnosed adult patients and for the treatment of patients with an accelerated phase. Imatinib is also approved for the treatment of patients with a certain type of gastrointestinal cancer (called stromal tumors) but it has not been approved to treat systemic sclerosis. Imatinib works by interfering with an enzyme called tyrosine phosphatase resulting in suppression of the immune system. It als interferes with a protein called platelet derived growth factor receptor (PDGFr) that has been linked to increased fibrosis.
Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs and widespread vasculopathy. Patients with SSc are classified according to the extent of cutaneous sclerosis: patients with limited SSc have skin thickening of the face, neck, and distal extremities, while those with diffuse SSc have involvement of the trunk, abdomen, and proximal extremities as well. The disease course varies depending on the subtype of SSc. However, common features that result in significant morbidity and mortality, in addition to cutaneous fibrosis, include Raynaud's phenomenon and digital ulcerations, interstitial lung disease (ILD), and pulmonary arterial hypertension (PAH). Current therapeutic options for patients with SSc and these clinical manifestations have shown limited efficacy. Imatinib antagonizes specific tyrosine kinases that mediate fibrotic pathways involved in the pathogenesis of SSc, including c-Abl, a downstream mediator of transforming growth factor (TGF)-beta, and platelet derived growth factor (PDGF) receptors. The efficacy of imatinib has also been reported in the treatment of patients with refractory idiopathic PAH through its effects on vascular remodeling. Based on the mechanism of action and preliminary patient data, we hypothesize that imatinib may be effective in the treatment of the fibrotic and vasculopathic features of patients with SSc. This is an open label pilot study to evaluate the safety and efficacy of imatinib in patients with progressive SSc refractory to other treatment(s). Validated measures of skin thickness and disease activity will be determined over 6-months of therapy and compared with baseline measures.
Systemic Sclerosis (Scleroderma) varies greatly in clinical manifestations, mode of presentation, and course. The natural history of this chronic autoimmune disease ranges from benign to fatal. Patients are classified into limited and diffuse scleroderma defined by the degree of skin involvement. Patients with limited disease (e.g. the C.R.E.S.T. syndrome) generally have mild disease and normal survival. However, patients with diffuse cutaneous scleroderma often have severe multi-system disease that is not only devastating emotionally and physically but is associated with a 60-70% five year survival and a 40-50% 10 year survival. No therapies have proven effective in the treatment of scleroderma. Strategy to treat scleroderma have included attempts to prevent fibrosis with drugs that interfere with collagen metabolism, attempts to modify the disease process by immunosuppression and attempts to alter the disease by vasoactive drugs. High dose of corticosteroids and other immunosuppressive drugs (e.g. chlorambucil, 5-fluorouracil, methotrexate, cyclophosphamide, cyclosporine) used at conventional doses have not proven curative, but have shown some benefit for inflammatory features of the disease (e.g. arthritis, myositis, fibrosing alveolitis). Both allogeneic and autologous bone marrow transplantation (BMT) have shown to modify and in some instances reverse a variety of animal models of autoimmune disease. This has prompted many investigators to propose the use of peripheral blood stem cell transplantation (PBSCT) for the treatment of autoimmune disease including scleroderma. Unfortunately, this approach risks infusing untreated autoreactive lymphocyte clones after the immunoablative preparative regimen. We have previously demonstrated that high-dose cyclophosphamide without BMT can induce durable and complete remissions in another autoimmune disease, severe aplastic anemia. Recent data with high dose cyclophosphamide show that it can induce complete remissions in other autoimmune hematologic disorders. The objective of this study is to determine whether high dose cyclophosphamide can induce a durable remission in scleroderma patients with life-threatening disease, and to determine toxicity of high dose cyclophosphamide in high risk scleroderma patients.
Raynaud's phenomenon is thought to occur when, in response to cold or emotional stress, there is closure of the digital arteries and cutaneous arterioles leading to the clinical finding of sharp demarcated digital pallor and cyanosis of the distal skin of the fingers and/or toes. Patients often continue to experience problems despite current available treatment. The investigators' study will investigate the use of a new vasodilator called Fasudil, a Rho-kinase inhibitor. The investigators' hypothesis is that Fasudil will prevent vasoconstriction of digital and cutaneous arteries during a standard laboratory based cold exposure and will therefore improve digital blood flow and skin temperature recovery time following cold challenge. These data will provide the rationale for a more elaborate clinical trials in real life situations.