Clinical trial NCT00657917: Topical Treatment of Recalcitrant Ulcerative Old World Leishmaniasis With WR 279,396
Official title: Topical Treatment of Recalcitrant Ulcerative Old World Leishmaniasis With WR 279,396
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cutaneous Leishmaniasis
Keywords: leishmaniasis
cutaneous
Old World
Leishmania major
Treatment
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
Collaborators: name: Walter Reed Army Medical Center
First posted: 2008-04-14
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Appearance of Complete Epithelialization of Ulcerative Lesions Caused by Old World Cutaneous Leishmaniasis With no Relapse
timeFrame: 180 days
Secondary outcomes:
measure: Number of Relapses
timeFrame: 180 days
measure: Safety and Tolerability (SAE's and AE's)
timeFrame: 180 days
Other outcomes:
Locations:
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
Study officials:
affiliation: Uniformed Services Univ of the Health Sciences
name: COL Naomi Aronson, M.D.
role: PRINCIPAL_INVESTIGATOR
References: