Local Heat Therapy Versus Sodium Stibogluconate for the Treatment of Cutaneous Leishmaniasis

Study Overview
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Brief Summary
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This study serves to compare the effectiveness of treating cutaneous leishmaniasis with either intravenous sodium stibogluconate or direct heat therapy using the ThermoMed-TM device.

Detailed Description
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A total of 56 Department of Defense health care beneficiaries, 18 years of age or older and diagnosed with cutaneous leishmaniasis, were planned to be treated with either intravenous sodium stibogluconate (Pentostam-TM) or the ThermoMed-TM device of Thermosurgery Technologies, Inc. at the Walter Reed Army Medical Center. Pentostam is the standard of care for this disease, but the i.v. administration and the many known side effects prompt the search for an improved method of treating this disease, especially for milder cases. This study compares the safety and efficacy of these two treatment approached.

Official Title
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A Phase I/II Randomized Comparison of Localized Heat Therapy Versus Sodium Stibogluconate (Pentostam) for the Treatment of Old World Cutaneous Leishmaniasis (HSRRB Log No. A-12364)

Conditions
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Cutaneous Leishmaniasis

Intervention / Treatment
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* Drug: Sodium stibogluconate (Pentostam)
* Device: ThermoMed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Department of Defense (DOD) Healthcare beneficiary Parasitologic diagnosis of cutaneous Leishmania infection (Inclusion criteria for randomization includes that must be Leishmania major species) Willing to locate to WRAMC area during treatment and perform subsequent follow-up visits if needed (If not active duty on orders, then the participant will bear the cost of food and lodging during the initial 10-day outpatient treatment period at Walter Reed Army Medical Center) Able to provide informed consent All participants (both male and female) must agree to take precautions not to become pregnant or father a child for at least 2 months after receiving sodium stibogluconate Exclusion Criteria: Unable to provide informed consent Pregnancy (females of child bearing potential must have negative urine human chorionic gonadotropic hormone [HCG] within 48 hours of the start of infusion period) History of hypersensitivity to pentavalent antimonials Serious medical illness: QTc interval >/= 0.5 sec severe cardiac disease history of current pancreatitis liver failure or active hepatitis with transaminases >3X normal renal failure or creatinine >2.5 thrombocytopenia (platelets <75,000) white blood cell count <2000 hematocrit <25 absence of palpable extremity pulses in the limb requiring treatment History of serious allergic reaction to local anesthetics Location of lesion not amenable to local therapy (such as close to eye, mucous membranes, face, cartilage) Presence of pacemaker and/or other implanted metallic devices Breast feeding Men unwilling to avoid fathering a child during and/or in the two months following receiving the treatment Women unwilling to avoid pregnancy for at least two months after receiving the treatment More than 20 lesions, or multiple lesions which in the opinion of the investigator would not be well treated with heat therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sodium stibogluconate intravenous<br>20 mg/kg/day Sodium stibogluconate intravenous | Drug: Sodium stibogluconate (Pentostam)<br>* intravenous 20 mg/kg/day for 10 days<br>* Other names: WR 229,870;|
| Experimental: ThermoMed device<br>ThermoMed device, single heat treatment at 50 degrees Celsius | Device: ThermoMed<br>* ThermoMed heat treatment device, one treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Equivalence of Efficacy Assessed by the Number of Participants With Clinical Cure | Assess whether local heat therapy using the ThermoMed device was equivalent (clinical cure) in efficacy to 10 days of parenteral sodium stibogluconate. Clinical cure is defined as complete epithelialization of lesion. post-treatment, photographs of treated lesions were assessed for efficacy outcome by a consensus decision of leishmaniasis experts blinded as to each subject's study group. On the basis of these photo assessments, clinical response was assessed by lesion and by subject. In addition, an overall response was assigned (healed or not healed) based on a combination of experts' photo assessments and subject interviews. Efficacy outcomes for the 2 study groups were compared using the Fishers exact test. | Assessment of cure is made at 2 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Equivalence of Efficacy (Clinical Cure) of TheroMed Treatment vs Sodium Stibogluconate Assessed by the Number of Subjects With Clinical Cure | Determine the equivalence of efficacy (clinical cure) of ThermoMed treatment vs sodium stibogluconate in clinical response of all skin lesions at 12 months. Clinical cure is defined as complete epithelialization of lesion. Post-treatment, photographs of treated lesions were assessed for efficacy outcome by a consensus decision of leishmaniasis experts blinded as to each subject's study group. On the basis of these photo assessments, clinical response was assessed by lesion and by subject. In addition, an overall response was assigned (healed or not healed) based on a combination of experts' photo assessments and subject interviews. Efficacy outcomes for the 2 study groups were compared using the Fishers exact test. | 12 months | 
| Number of Participants With Solicited Adverse Events | To compare the toxicity profiles of ThermoMed treatment versus parenteral sodium stibogluconate therapy thru specific solicited adverse events | Days 3, 7 and 10 | 
| Immune Response, Based on T-Cell Population Before Treatment, and Day 10 Following Treatments | Evaluate the immune response (T-Cell population) to Leishmania before treatment, and at 10 days, in recipients of localized heat therapy vs systemic sodium stibogluconate. Days 1 and 10 are presented in columns. | day 1 and day 10 | 
| Immune Response, Based on Percent of T-Cell Population Before Treatment, and Day 10 Following Treatments | Evaluate the immune response (T-Cell population) to Leishmania before treatment, and at 10 days, in recipients of localized heat therapy vs systemic sodium stibogluconate. Days 1 and 10 are presented in columns. | day 1 and day 10 | 
| Feasibility of a L. Major Species Specific Polymerase Chain Reaction as a Rapid Diagnostic Device in the Context of a Treatment Trial | Evaluate the feasibility of using species-specific PCR as a rapid diagnostic assay for L. major infection. The comparator modalities were: histopathology (identification of amastigotes); speciation determined through culture and isoenzyme analysis; and genus and species-specific PCR. Species PCR testing was performed at baseline to allow for the identification of L. major as each subject's infecting parasite. If an L. major infection could not be confirmed in a subject's lesion(s), then that subject could not be treated under this protocol. | at baseline before treatment |