Efficacy of Topical Liposomal Form of Drugs in Cutaneous Leishmaniasis

Pilot Study of Efficacy of Topical Nano-liposomal Meglumine Antimoniate (Glucantime) or Paromomycin in Combination With Systemic Glucantime for the Treatment of Anthroponotic Cutaneous Leishmaniasis (ACL) Caused by Leishmania Tropica

Leishmaniasis with diverse clinical manifestations is caused by different species of Leishmania and is endemic in many countries. Although Cutaneous Leishmaniasis (CL) is a self-healing disease, but it takes a long time to heal. Pentavalent antimonials are still the first-line treatment of CL which needs multiple injections, are painful and as such not tolerated by most of the patients, in addition available treatments are not always effective and resistance is reported. Paromomycin sulfate (PM) reported to show anti-Leishmania activity against both CL and visceral leishmaniasis (VL) since 1960s. Therapeutic strategy with high efficacy is urgently needed especially for Anthroponotic Cutaneous Leishmaniasis (ACL). Liposomes are lipid bilayer molecules which entrap water-soluble molecules in their internal water compartment and water-insoluble ones into their lipid bilayers. Liposomes, in proper formulations and sizes, deliver drugs to the skin based on the similarity of the bilayers structure of lipid vesicles to that of natural membrane and target the macrophages within dermis. Several lipid-based formulations have been developed to treat experimental leishmaniasis. Recently different doses of liposomal formulation of PM and liposomal formulation of Glucantime were prepared and showed high efficacy in vivo against L. major infection in BALB/c mice.

In this study the efficacy of liposomal formulation of PM or liposomal formulation of Glucantime in combination with systemic Glucantime in the treatment of ACL parasitologically proven patients will be evaluated. The clinical trial will be carried out according to the International approved GCP (Good Clinical Practice) guide lines.

Study Overview

• Status: Completed
• Conditions: Cutaneous Leishmaniasis
• Intervention / Treatment: Drug: Placebo; Drug: Liposomal meglumine antimoniate; Drug: Liposomal Paromomycin; Drug: Liposomal meglumine antimoniate (Glucantime)

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Khorasan Razavi
    • Mashhad, Khorasan Razavi, Iran, Islamic Republic of
      • Emam Reza Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 56 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female aged between 12 to 60 years.
• Parasitologically proven CL due to L. tropica.
• History of failure to at least one full course of systemic Glucantime.
• In general good health based on history and physical examination.
• Number of lesion at most 4.
• Lesion size less than 3 cm.

• Signed informed consent voluntarily and knowingly.

  • Guardian's signature for volunteer less than 18 years old.

Exclusion Criteria:

• Pregnant or lactating women and those who are planning to be pregnant in next 60 days.
• Use of other types of treatment for CL.
• Involvement in any other drug or vaccine trial during the study period.
• Known heart, kidney, liver diseases based on history and physical exam. Abnormal ECG.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo; Drug: Liposomal meglumine antimoniate; Liposomal form of meglumine antimoniate
Experimental: Liposomal Paromomycin; Liposomes containing 10% Paromomycin	Drug: Liposomal meglumine antimoniate; Liposomal form of meglumine antimoniate; Drug: Liposomal Paromomycin; Liposomal form of 10% Paromomycin
Experimental: Liposomal meglumine antimoniate; Liposomes containing meglumine antimonate	Drug: Liposomal meglumine antimoniate; Liposomal form of meglumine antimoniate; Drug: Liposomal meglumine antimoniate (Glucantime); Liposomes containing meglumine antimoniate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete cure equal to Complete Re-epithelization of all lesions	200 days

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Collaborators: Mashhad University of Medical Sciences; Center for Research and Training in Skin Diseases and Leprosy
• Investigators: Principal Investigator: Masud Maleki, MD, Mashhad University of Medical Sciences, Mashhad, Iran; Principal Investigator: Ali Khamesipour, MPH, PhD, Center for Research & Training in Skin Diseases & Leprosy, TUMS; Principal Investigator: Mahmoud Reza Jaafari, Parm D, PhD, Mashhad University of Medical Sciences, Mashhad, Iran

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: January 13, 2010
• First Submitted That Met QC Criteria: January 14, 2010
• First Posted (Estimate): January 15, 2010

Study Record Updates

• Last Update Posted (Estimate): June 20, 2012
• Last Update Submitted That Met QC Criteria: June 19, 2012
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: Cutaneous Leishmaniasis caused by l. tropica
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Euglenozoa Infections; Leishmaniasis; Leishmaniasis, Cutaneous; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Paromomycin; Meglumine Antimoniate
• Other Study ID Numbers: 86783