Cutaneous Leishmaniasis
Conditions
Keywords
leishmaniasis, cutaneous, Old World, Leishmania major, 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.
Interventions
DRUGParomomycin +Gentamicin topical cream
WR297,396 for treatment of patients with parasitologically confirmed, primarily ulcerative, Old World CL, who had either failed pentavalent antimony treatment, or who where ineligible for pentavalent antimony therapy.
Sponsors
Walter Reed Army Medical Center
U.S. Army Medical Research and Development Command
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Appearance of Complete Epithelialization of Ulcerative Lesions Caused by Old World Cutaneous Leishmaniasis With no Relapse | 180 days | Appearance of complete (100%) epithelialization of a skin lesion at day 50+2 weeks, or the estimated 50%-99% re-epithelialization by day 50+2 weeks followed by complete eipithelialization by day 100+2 weeks, with both categories without relapse by day 180+30 days. Ulcer measured in millimeters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Relapses | 180 days | Evaluate the number of relapses occurring by day 180 |
| Safety and Tolerability (SAE's and AE's) | 180 days | Evaluate safety and tolerability as measured by completion of a full prescribed treatment course, treatment interruptions, SAE's and AE's |
Countries
United States
Participant flow
Recruitment details
Recruitment was conducted at Walter Reed Army Medical Center, Washington, DC. One subject was enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Paromomycin +Gentamicin Topical Cream WR279,396 topically twice a day for 20 days
Paromomycin +Gentamicin topical cream: WR297,396 for treatment of patients with parasitologically confirmed, primarily ulcerative, Old World CL, who had either failed pentavalent antimony treatment, or who where ineligible for pentavalent antimony therapy. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Paromomycin +Gentamicin Topical Cream |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
The Appearance of Complete Epithelialization of Ulcerative Lesions Caused by Old World Cutaneous Leishmaniasis With no Relapse
Appearance of complete (100%) epithelialization of a skin lesion at day 50+2 weeks, or the estimated 50%-99% re-epithelialization by day 50+2 weeks followed by complete eipithelialization by day 100+2 weeks, with both categories without relapse by day 180+30 days. Ulcer measured in millimeters.
Time frame: 180 days
Population: Ultimately, the planned statistical analysis could not be performed because only one patient was enrolled in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paromomycin +Gentamicin Topical Cream | The Appearance of Complete Epithelialization of Ulcerative Lesions Caused by Old World Cutaneous Leishmaniasis With no Relapse | Screening | 2,142 Surface area in millimeters squared |
| Paromomycin +Gentamicin Topical Cream | The Appearance of Complete Epithelialization of Ulcerative Lesions Caused by Old World Cutaneous Leishmaniasis With no Relapse | Day 20+3 | 1,488 Surface area in millimeters squared |
| Paromomycin +Gentamicin Topical Cream | The Appearance of Complete Epithelialization of Ulcerative Lesions Caused by Old World Cutaneous Leishmaniasis With no Relapse | Day 50+14 | 1,400 Surface area in millimeters squared |
| Paromomycin +Gentamicin Topical Cream | The Appearance of Complete Epithelialization of Ulcerative Lesions Caused by Old World Cutaneous Leishmaniasis With no Relapse | Day 180+30 (photos only) | 0 Surface area in millimeters squared |
Secondary
Number of Relapses
Evaluate the number of relapses occurring by day 180
Time frame: 180 days
Population: Ultimately, the planned statistical analysis could not be performed because only one patient was enrolled in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paromomycin +Gentamicin Topical Cream | Number of Relapses | 0 Number of relapses |
Secondary
Safety and Tolerability (SAE's and AE's)
Evaluate safety and tolerability as measured by completion of a full prescribed treatment course, treatment interruptions, SAE's and AE's
Time frame: 180 days
Population: Ultimately, the planned statistical analysis could not be performed because only one patient was enrolled in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paromomycin +Gentamicin Topical Cream | Safety and Tolerability (SAE's and AE's) | AEs Considered Related to Study Drug | 9 Number of AE's |
| Paromomycin +Gentamicin Topical Cream | Safety and Tolerability (SAE's and AE's) | AE's Not Considered Related to Study Drug | 23 Number of AE's |