Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01464242
Other study ID # 222951928964
Secondary ID
Status Completed
Phase Phase 2/Phase 3
First received October 24, 2011
Last updated August 22, 2016
Start date November 2011
Est. completion date December 2015

Study information

Verified date August 2016
Source Centro Internacional de Entrenamiento e Investigaciones Médicas
Contact n/a
Is FDA regulated No
Health authority Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Study type Interventional

Clinical Trial Summary

The purpose of this study is to determine whether adding pentoxifylline to treatment of American cutaneous leishmaniasis with meglumine antimoniate increases the rate and speed of clinical response without diminishing safety, and to identify immune correlates of the healing response.


Description:

Failure of first line therapies for cutaneous leishmaniasis is a public health issue. Since pathogenesis of dermal leishmaniasis is mediated by the immune and inflammatory responses, resolution of disease and control of infection are intimately linked to the host response. Several investigations have substantiated "proof of principal" for the therapeutic gain of co-adjuvant immunotherapy. This study will evaluate the efficacy and safety of using pentoxifylline (PTX) as a co-adjuvant in the treatment of cutaneous leishmaniasis with meglumine antimoniate in a randomized, double-blind, controlled trial. One arm will receive meglumine antimoniate and PTX and the other arm will receive meglumine antimoniate plus placebo. Efficacy will be assessed at the end of the treatment, and 5, 7, 13 and 26 weeks after initiation of treatment. Efficacy will be measured as the proportion of patients with definitive cure at 26 weeks after initiation of treatment, and time to healing. Safety will be assessed at the end of treatment with respect to the frequency and severity of adverse events.

Blood samples will be taken to evaluate the effects of PTX invitro and ex vivo on cells of the immune system. Proliferation and secretion of cytokines relevant to the immune and inflammatory responses by peripheral blood mononuclear cells will be measured before and after treatment. Likewise, macrophages will be differentiated from peripheral blood monocytes and infected with a strain of L. panamensis transfected with the luciferase (luc) gene. The investigators will measure the capacity of patient macrophages to kill parasites before and after treatment using a luminometric assay of viable parasite burden. Additionally, the investigators will measure the expression of inducible nitric oxide synthase, an enzyme that is necessary for nitric oxide production, one of the main leishmanicidal mechanisms used by macrophages. The investigators postulate that the use of the co-adjuvant with antimonials will increase the therapeutic response and that indicators predictive of a healing response can be identified by this prospective analysis of the immune response and therapeutic outcome.


Recruitment information / eligibility

Status Completed
Enrollment 75
Est. completion date December 2015
Est. primary completion date January 2015
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria:

- Patients with clinical diagnosis of cutaneous leishmaniasis (parasitologic confirmation or presumptive biopsy plus a positive Montenegro skin test).

- Age between 18 and 65 years.

- Lesions of a duration equal to or greater than one month

- More than one lesion or single lesion greater than 3 cm in diameter.

- Willingness to participate in the study after being informed through a consent process approved by the institutional ethical review committee

Exclusion Criteria:

- Pregnant or lactating women, and women who are planning to conceive during the study or that reject the use of birth control methods.

- Medical conditions that compromise the immune system (HIV infection, neoplasias, diabetes mellitus, autoimmune diseases, or use of corticosteroids, immunomodulators or antineoplastic drugs).

- Medical conditions that preclude the use of antimonials or pentoxifylline (cardiac, renal, hepatic or pancreatic disease or abnormalities).

- Alcohol abuse or use of recreational drugs that interfere with adherence to treatment

- Use of drugs with antileishmanial potential during the previous 13 weeks, including pentavalent antimonials, amphotericin B, miltefosine, and pentamidine

- Use of Theophylline , anticoagulants or antiarrhythmics.

- Diffuse or disseminated leishmaniasis.

- Mucosal involvement secondary to Leishmania infection.

- Incapacity to attend the study visits or any other condition that according to the investigator could interfere with adherence to study procedures.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment


Intervention

Drug:
Meglumine antimonate
Glucantime® 20mg/kg/day IM daily for 20 days
Placebo
Placebo 400mg orally 3 times a day for 20 days
Pentoxifylline
Pentoxifylline 400mg orally 3 times a day for 20 days

Locations

Country Name City State
Colombia Corporación Centro Internacional de entrenamiento e Investigaciónes Médicas Cali Valle

Sponsors (1)

Lead Sponsor Collaborator
Centro Internacional de Entrenamiento e Investigaciones Médicas

Country where clinical trial is conducted

Colombia, 

Outcome

Type Measure Description Time frame Safety issue
Primary Primary efficacy outcome: Definitive Cure Definitive cure, defined as complete re-epithelialization and absence of inflammatory signs in all cutaneous leishmaniasis lesions, and absence of new leishmaniasis lesions Participants will be followed up to 26 weeks No
Primary Primary safety outcome: Adverse Events Clinical and laboratory adverse events will be qualified according to the Common Toxicity Criteria for Adverse Effects (CTCAE). All unexpected non serious adverse events will be notified and expected adverse events of moderate or higher category will be reported. All serious adverse events will be reported. Participants will be followed up to 26 weeks Yes
Secondary In vitro lymphoproliferation Proliferation of peripheral blood mononuclear cells (PBMCs) after stimulation invitro with L. panamensis antigens will be measured by tritiated thymidine uptake Participants will be followed for an average of 20 days No
Secondary Cytokine secretion by PBMCs Secretion of a panel of cytokines relevant to the inflammatory and immune responses will be measured in supernatants from PBMCs cultured with L. panamensis antigens using Luminex technology Participants will be followed for an average of 20 days No
Secondary Macrophage leishmanicidal capacity Macrophages will be differentiated from peripheral blood monocytes and their leishmanicidal capacity will be measured by luminometry after infecton with luciferase-transfected promastigotes. Participants will be followed for an average of 20 days No
Secondary Macrophage inducible nitric oxide synthase (iNOS) expression Macrophage expression of iNOS after infection will be measured by quantitative real-time Polymerase Chain Reaction (RT-PCR). Participants will be followed for an average of 20 days No
See also
  Status Clinical Trial Phase
Completed NCT01988909 - WR 279,396 for the Treatment of Cutaneous Leishmaniasis Phase 2
Enrolling by invitation NCT00840359 - Study of the Efficacy of Daylight Activated Photodynamic Therapy in the Treatment of Cutaneous Leishmaniasis Phase 2
Enrolling by invitation NCT00737386 - Frequency of Parasite Infection in Hyraxes and Sandflies During Outbreak of Leishmania Tropica Epidemic in The West Bank N/A
Completed NCT00233545 - Miltefosine to Treat Cutaneous Leishmaniasis in Bolivia Phase 2
Completed NCT01462500 - Pharmacokinetics of Miltefosine in Children and Adults Phase 4
Completed NCT01011309 - A Study of the Efficacy and Safety of the LEISH-F2 + MPL-SE Vaccine for Treatment of Cutaneous Leishmaniasis Phase 2
Completed NCT01301924 - Comparison of Standard and Alternative Antimonial Dosage in Patients With American Cutaneous Leishmaniasis Phase 2/Phase 3
Not yet recruiting NCT02281669 - Prospective Observational Study of Intralesional Treatment With Pentostam in Cutaneous Leishmaniasis Israeli Patients N/A
Completed NCT01790659 - Phase 3 Study of Walter Reed (WR) 279,396 and Paromomycin Alone for the Treatment of Cutaneous Leishmaniasis in Panama Phase 3
Completed NCT01050907 - Miltefosine to Treat Mucocutaneous Leishmaniasis Phase 2
Completed NCT04340128 - Efficacy of Intra-lesional Injections of Glucantime Once a Week or Twice a Week in the Treatment of Anthroponotic Cutaneous Leishmaniasis (ACL) Phase 3
Terminated NCT00317629 - Controlled Nitric Oxide Releasing Patch Versus Meglumine Antimoniate in the Treatment of Cutaneous Leishmaniasis Phase 3
Completed NCT00351520 - Efficacy Trial on Oral Miltefosine in Comparison With Glucantime in the Treatment of ACL Caused by L. Tropica Phase 3
Completed NCT01381055 - Antimony Plus Pentoxifylline in Cutaneous Leishmaniasis Phase 2/Phase 3
Completed NCT01050777 - Efficacy of Topical Liposomal Form of Drugs in Cutaneous Leishmaniasis Phase 0
Completed NCT01380314 - Oral Miltefosine Plus Topical Imiquimod to Treat Cutaneous Leishmaniasis Phase 2
Terminated NCT01380301 - Treatment of Cutaneous Leishmaniasis With a Combination of Miltefosine and Antimony Phase 2
Completed NCT00703924 - Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: A Phase 2 Study in the Old World Phase 2
Completed NCT00344084 - Surveillance for Leishmaniasis Skin Lesions in Mali
Completed NCT03023111 - Miltefosine and GM-CSF in Cutaneous Leishmaniasis Phase 3