View clinical trials related to Leishmaniasis.
Filter by:Background: - Visceral leishmaniasis (VL) is an infection caused by parasites carried by sand flies. The parasites cause fever, weight loss, and enlargement of the spleen and liver. They can also affect the blood and immune system. One possible treatment for VL involves an experimental drug called SCH708980, which may help to prevent the immune system from becoming suppressed and worsening the VL. Researchers want to give the drug along with AmBisome(Registered Trademark), which kills the parasites, to see if it is a safe and effective treatment. Objectives: - To study the safety and effectiveness of SCH708980, alone and combined with AmBisome(Registered Trademark), as a treatment for visceral leishmaniasis. Eligibility: - Individuals 18 to 60 years of who have been diagnosed with visceral leishmaniasis in the past 4 to 5 days, are HIV-negative, and are willing to stay in the hospital for 30 days. - All participants will come from and be treated at the Kala-Azar Medical Research Center in Muzaffarpur, India. Design: - This is a two-part study. Participants will be assigned to only one part of the study. - Participants will be screened with a medical history and physical exam; blood, urine, and stool samples, spleen or bone marrow samples; spleen measurements; a chest xray; and a heart function test. - Part 1 participants will be separated into two groups: a larger group will have a selected dose of the study drug followed by AmBisome 7 days later, and a smaller group will have a placebo treatment followed by AmBisome. - Part 2 participants will have either the study drug or a placebo plus AmBisome, based on the test results from the Part 1 participants. - All participants will be monitored in the hospital for 30 days, and will have the following tests: - Regular blood samples - Urine and stool samples (day 14) - Spleen measurements (days 8, 14, 21, and 30) - Spleen or bone marrow sample (day 30 only). Participants who still have VL symptoms will give another sample on day 45. - At 6 months after the start of treatment, participants will have a follow-up visit with spleen measurements, blood and stool samples, and possible spleen or bone marrow samples
The purpose of this study is to determine whether pentoxifylline associated to pentavalent antimony has a higher cure rate than pentavalent antimony alone in the treatment of cutaneous leishmaniasis.
Cutaneous leishmaniasis is endemic in the New World from approximately the US-Mexican border through Central America and the Northern part of South America down to the level of Rio de Janeiro. Until recently, the standard treatment for the leishmaniases was pentavalent antimony (Glucantime or Pentostam). The cure rate for L panamensis in Colombia is 91%-93% [Soto, 1993; Velez, 1997], a large study with several formulations of antimony found a combined Bolivia-Colombia cure rate of 86% [Soto, 2004b], and in work just completed, the cure rate in Palos Blancos, Bolivia is 15 of 16 = 94% [ Soto, manuscript in preparation]. Nevertheless, pentavalent antimonials have the disadvantages of multiple injections and mild-moderate clinical toxicity [gastrointestinal complaints, liver enzyme elevations, pancreatic enzyme elevations], all of which are particularly unpleasant for a moderate clinical problem such as cutaneous leishmaniasis. The oral agent Miltefosine has now been shown to be as effective as antimony in Colombia and Bolivia. In Colombia, the cure rate for miltefosine was 91% [Soto 2004a] and in the just-completed trial in Palos Blancos, the cure rate for miltefosine was 32 of 37 = 88 % . Side effects seen in patients with cutaneous disease that can be specifically attributed to the drug are nausea and vomiting of mild grade in approximately 25% of patients, and low-grade elevation of creatinine also in approximately 25% of patients [Soto 2001; Soto 2004]. The 6-month cure rate did not reach 100%, and miltefosine was relatively slow to cure compared to Sb. 31 of 44 evaluable miltefosine patients (70%) were cured by 1 month after therapy, compared to 16 of 16 evaluable Glucantime patients (100%). Imiquimod (Aldara; 3M Pharmaceuticals) is a novel immune response-activating compound, approved by the FDA for cervical warts, that activates macrophage killing of Leishmania species. Combined imiquimod plus Glucantime was used as rescue treatment in 12 patients with Peruvian cutaneous leishmaniasis who had previously not responded to Glucantime alone. 90% of patients were cured at the 6-month follow-up period [Arevalo, 2001]. In a follow up study [Miranda-Verastegui et al, 2005], naïve patients were randomized between the combination of Sb plus imiquimod (18 patients) vs Sb plus placebo (20 patients). The cure rate at 1 month after therapy was 50% in the imiquimod +Sb group compared to 15% in the placebo+Sb group (p = 0.02). By 12 months after therapy, the Sb+placebo group had caught up, and the cure rate was 72%-75% in each group. Local side effects were evaluated. Edema, itching, burning, pain were equal in the two groups. There was more erythema in the imiquimod grup (55% of patients) compared to the placebo group (25% of patients). The Imiquimod studies in neighboring Peru suggest that combination with this immunomodulator is capable of decreasing the time to cure, and potentially increasing the cure rate, in Andean cutaneous leishmaniasis. The present study will evaluate the combination of oral miltefosine plus topical imiquimod for cutaneous leishmaniasis in Bolivia. If in the first group of patients, cure rate at 1 month after therapy is appreciably above the 70% historic value for miltefosine alone and the cure rate at 6 months is greater than the 88% historic value for miltefosine alone, subsequent patients will be randomized between miltefosine+imiquimod and miltefosine+placebo cream.
Cutaneous leishmaniasis is endemic in the New World and, until recently, the standard treatment was pentavalent antimony. The cure rate for L panamensis in Colombia is 91%-93% and the cure rate in Bolivia is also 90%. Nevertheless, pentavalent antimonials have the disadvantages of multiple injections and mild-moderate clinical toxicity all of which are particularly unpleasant for a moderate clinical problem such as cutaneous leishmaniasis. The oral agent Miltefosine has now been shown to be as effective as antimony in Colombia and Bolivia (91 and 92% respectively). Side effects seen in patients with cutaneous disease that can be specifically attributed to the drug are nausea and vomiting of mild grade in approximately 25% of patients, and low-grade elevation of creatinine also in approximately 25% of patients. A further disadvantage of miltefosine is that regimens shorter than 4 weeks have not been evaluated for cutaneous disease. Combination therapy is now being used for many infectious diseases, such as tuberculosis, malaria, and HIV. Combination therapy offers the potential of preventing drug resistance, because organisms resistant to one of the drugs may be susceptible to the other drug; and also the potential to diminish drug therapy duration and thus side effects. These two potential benefits to some extent contradict each other: preventing resistance is best done if full courses of both drugs is used; diminishing therapy duration means using less than the full course of each drug. The optimum combination regimen is one in which sufficient amounts of both drugs are used to have high efficacy, yet the amounts are as low as possible to spare patients unnecessarily long courses of drug. In the present protocol, the combination of a half-course of miltefosine and a half-course of antimony will be evaluated for efficacy and tolerance. The combination of miltefosine and antimony is chosen because these are now the two standard agents in Bolivia, and in vitro the combination was additive to mildly synergistic against a standard leishmania strain.
The purpose of this study is to determine whether miltefosine is effective in the treatment of mucosal leishmaniasis compared to meglumine antimoniate, the standard treatment.
Visceral leishmaniosis (VL) is widely reported in Ethiopia, with about 30% of cases being associated with human immunodeficiency virus (HIV). In absence of antiretroviral treatment (ART), poor prognosis, high mortality and high relapse rates are characteristic of Ethiopian VL patients with HIV co-infection. Conversely, co-infection can be successfully managed via a combination of effective treatment of the initial episode, timely ART and prevention of relapses. Actually, until cellular immunity returns with ART, the patient is at risk of VL relapses, which can result in death, severe illness, reduced ART efficacy, drug-resistance and possibly transmission of drug-resistant Leishmania donovani. Patients most vulnerable to relapses are those with high levels of immunosuppression, with previous VL episodes, or with opportunistic infections (OIs). The most important factor to prevent relapses seems to be the clearance of visible parasites. Limited studies in Europe show that HIV co-infected patients may benefit from secondary prevention with antimonials (part of mainstay treatment for VL in Ethiopia) and pentamidine (PM), not used for VL treatment in Africa. Such maintenance treatment has not been studied in African VL, but the poor outcomes without secondary prevention highlight a need of better care to patients at risk of relapse. This prospective cohort study aims at documenting the patient's outcomes of secondary prophylaxis with PM in VL-HIV co-infection, in terms of time to relapse or death, safety and feasibility, before it can be considered for general use in Ethiopia. A placebo group is not included, due to the clear advantages of the intervention to the patient population.
The purpose of this study is to evaluate the effectiveness of treatment with PMIM in patients with visceral leishmaniasis within the VL-endemic region of Bangladesh at EOT (21/22 days after treatment begins), and at 6 months after end of treatment (Day 202/203, -15 to +30 days).
This study is aimed to compare the efficacy and safety of medications currently used in Brazil for treatment of visceral leishmaniasis. The investigators will compare the effects of meglumine antimoniate, two formulations of amphotericin B: deoxycholate and liposomal, and a combination of meglumine plus the liposomal amphotericin B formulation. The study is designed to demonstrate the difference in efficacy measured as cure rate at six months after treatment and the safety profile based on the adverse event rate observed with each intervention.
"Phase III clinical trial for mucosal or mucocutaneous leishmaniasis. Equivalence between the standard and alternative schemes with meglumine antimoniate" has begun in October 2008 at the Laboratory of Leishmaniasis Surveillance at Evandro Chagas Clinical Research Institute (IPEC), FIOCRUZ, aiming to compare efficacy and safety of the standard recommended schedule with an alternative regimen of meglumine antimoniate (MA) in the treatment of mucosal or mucocutaneous leishmaniasis (ML or MCL)). It is a study with blind evaluation by the doctors and the responsible for statistical analysis. Patients diagnosed with Ml or MCL, eligible for the trial, are randomly allocated into one of the schemes with meglumine antimoniate and monitored before, during and after it. There is no single regimen applicable to all forms of leishmaniasis around the world. Therapeutic regimens applied to treat people living in other geographic areas result in mixed outcomes. Ideally, the most appropriate regimens should be established for each endemic area, based on its efficacy, toxicity, difficulties of administration and cost. Given the problems and limitations of the use of pentavalent antimonials at 20 mg / kg / day, a less toxic alternative regimen with 5mg/kg/day, continuous up to the cure deserves to be better evaluated. Treatment must lead to the healing of mucosal lesions and prevent late scarring tissues and disabilities development. The indication of high doses of MA is based on the evidence that there could be induction of resistance with use of subdoses. However, clinical studies with extended follow-up in Rio de Janeiro have suggested that regular low MA doses (5mg / kg / day) in a systemic way may constitute an effective scheme, achieving cure rates similar to higher dose, with lower toxicity, ease of implementation and lower cost. Published studies on efficacy and safety of alternative schemes with meglumine antimoniate failed to provide conclusive results, for various methodological biases. The need to compare the effectiveness and safety between treatment schemes with meglumine antimoniate currently recommended in Brazil for the treatment of ML or MCL and an alternative scheme with low dose of antimony is the motive for this study in Rio de Janeiro.
"Phase III Clinical Trial for American Tegumentary Leishmaniasis: Comparison of Standard and Alternative Antimonial Dosage in Patients With American Cutaneous Leishmaniasis " has begun in October 2008 at the Laboratory of Leishmaniasis Surveillance at Evandro Chagas Clinical Research Institute (IPEC), FIOCRUZ, aiming to compare efficacy and safety of the standard recommended schedule with an alternative dosage scheme of meglumine antimoniate in the treatment of American tegumentary leishmaniasis (ATL). It is a study with blind evaluation by the doctors and the responsible for statistical analysis. Patients diagnosed with ATL, eligible for the trial are randomly allocated into one of the schemes with meglumine antimoniate and monitored before, during and after it. There is no single regimen applicable to all forms of leishmaniasis around the world. Therapeutic regimens applied to treat people living in other geographic areas result in mixed outcomes. Ideally, the most appropriate regimens should be established for each endemic area, based on its efficacy, toxicity, difficulties of administration and cost. Given the problems and limitations of the use of pentavalent antimonials (Sb5+) at 20 mg Sb5+ / kg / day, less toxic alternative regimens, i.e. 5mg Sb5+/kg/day, deserve to be better evaluated. The treatment of ATL must heal skin lesions and prevent late mucosal lesion development. The indication of high doses of Sb5+ is based on the evidence that there could be induction of resistance with use of subdoses. However, clinical studies with extended follow-up in Rio de Janeiro have suggested that regular low doses (5mg Sb5+ / kg / day) may constitute an effective scheme, achieving cure rates similar to higher doses, with lower toxicity, ease of implementation and lower cost. Published studies on efficacy and safety of alternative dosage schemes with meglumine antimoniate failed to provide conclusive results so far, for various methodological biases. The need to compare the effectiveness and safety between the standard treatment scheme with meglumine antimoniate currently recommended in Brazil for the treatment of ATL and an alternative scheme with low doses of antimony is the motive for this study in Rio de Janeiro.