Topical Treatment of Recalcitrant Ulcerative Old World Leishmaniasis With WR 279,396

United States Army Medical Research and Development Command (USAMRDC)

Status and phase

Terminated

Phase 2

Conditions

Cutaneous Leishmaniasis

Treatments

Drug: Paromomycin +Gentamicin topical cream

Study type

Interventional

Funder types

Other U.S. Federal agency

Identifiers

NCT00657917

A-13225

Details and patient eligibility

About

The primary objective of this protocol is to treat laboratory confirmed cutaneous leishmaniasis with WR 279,396 in military health care beneficiaries. In this study "cutaneous leishmaniasis" is defined as Old World Leishmaniasis if acquired in the Southwest Central Asia/Middle East.

Full description

Up to 10 volunteers, who are military health care beneficiaries, with a diagnosis of Old World cutaneous leishmaniasis who have failed pentavalent antimony or are not eligible to be treated with pentavalent antimony, will be treated with WR 279,396 (topical paromomycin-gentamicin-AQIC) twice a day for 20 days. Primary endpoint will be the appearance of complete epithelialization of each skin lesion by Day 50+/-2 weeks, or estimated 50%-99% re-epithelialization by Day 50+/-2 weeks followed by complete epithelialization by Day 100+/-2 weeks,with both categories without relapse by Day 180+/-30 days. Efficacy will be evaluated by clinical appearance assessed by study investigator and documented with photographs of the treated skin lesions. Toxicity will be evaluated by local adverse reactions and by laboratory signs of systemic toxicity.

Enrollment

1 patient

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Parasitologically confirmed, primarily ulcerative, Old World CL, in a patient who had either failed pentavalent antimony treatment, or who was ineligible for pentavalent antimony therapy.

Military health care beneficiary 18 years of age or greater, unless active military in which case, 17 years is the minimum age
Proven parasitological diagnosis by culture, PCR or microscopy in at least one skin lesion
Lesions primarily ulcerative (i.e., not verrucous or nodular)
Written informed consent to participate in protocol
Negative pregnancy test within 72 hours of starting protocol
Agrees to take precautions not to become pregnant or father a child for at least two months after completion of treatment with WR 279,396
Cutaneous leishmaniasis acquired in Southwest Central Asia/Middle East*
Inadequate response to treatment with pentavalent antimony or medical condition that precludes the use of pentavalent antimony

Exclusion criteria

Drug intolerance: history of known or suspected hypersensitivity or idiosyncratic reactions to aminoglycosides in the patient
any leishmanial lesion on mucosal surface
Presence of signs or symptoms of peripheral neuropathic myasthenia gravis, neuromuscular block
Routinely taking nephrotoxic or ototoxic medications
Disseminated disease defined as clinically significant subcutaneous nodules that are in the lymphatic drainage tract for the skin lesion with regional adenopathy > 1 cm
Abnormal Romberg test at baseline
Clinically significant medical problems of the kidney or liver as determined by history and by the following laboratory studies:
- Kidney: Creatinine > 2x the upper limit of normal
- Liver: ASTor ALT >4x the upper limit fo normal
  - This includes "L. major," "L. tropica," and "L. infantum" with over 98% of cases in U.S. military in 2002-2004 being "L. major"
    - An inadequate response to treatment with pentavalent antimony includes patients who show no or little improvement during a 15-20 day treatment course, those that initially epithelialize but later show signs of breakdown/ ulceration or develop new lesions. In general, for those with initial treatment response, would recommend waiting for approximately two months after pentavalent antimony and if lesion is not epithelialized at that time, consideration for further therapy is advised.