Cutaneous Leishmaniasis Clinical Trial
Official title:
Treatment of Bolivian Cutaneous Leishmaniasis With a Combination of Oral Miltefosine Plus Topical Imiquimod 5%
Verified date | June 2011 |
Source | Foundation Fader |
Contact | n/a |
Is FDA regulated | No |
Health authority | Bolivia: Ministry of Health |
Study type | Interventional |
Cutaneous leishmaniasis is endemic in the New World from approximately the US-Mexican border
through Central America and the Northern part of South America down to the level of Rio de
Janeiro.
Until recently, the standard treatment for the leishmaniases was pentavalent antimony
(Glucantime or Pentostam). The cure rate for L panamensis in Colombia is 91%-93% [Soto,
1993; Velez, 1997], a large study with several formulations of antimony found a combined
Bolivia-Colombia cure rate of 86% [Soto, 2004b], and in work just completed, the cure rate
in Palos Blancos, Bolivia is 15 of 16 = 94% [ Soto, manuscript in preparation].
Nevertheless, pentavalent antimonials have the disadvantages of multiple injections and
mild-moderate clinical toxicity [gastrointestinal complaints, liver enzyme elevations,
pancreatic enzyme elevations], all of which are particularly unpleasant for a moderate
clinical problem such as cutaneous leishmaniasis.
The oral agent Miltefosine has now been shown to be as effective as antimony in Colombia and
Bolivia. In Colombia, the cure rate for miltefosine was 91% [Soto 2004a] and in the
just-completed trial in Palos Blancos, the cure rate for miltefosine was 32 of 37 = 88 % .
Side effects seen in patients with cutaneous disease that can be specifically attributed to
the drug are nausea and vomiting of mild grade in approximately 25% of patients, and
low-grade elevation of creatinine also in approximately 25% of patients [Soto 2001; Soto
2004].
The 6-month cure rate did not reach 100%, and miltefosine was relatively slow to cure
compared to Sb. 31 of 44 evaluable miltefosine patients (70%) were cured by 1 month after
therapy, compared to 16 of 16 evaluable Glucantime patients (100%).
Imiquimod (Aldara; 3M Pharmaceuticals) is a novel immune response-activating compound,
approved by the FDA for cervical warts, that activates macrophage killing of Leishmania
species. Combined imiquimod plus Glucantime was used as rescue treatment in 12 patients with
Peruvian cutaneous leishmaniasis who had previously not responded to Glucantime alone. 90%
of patients were cured at the 6-month follow-up period [Arevalo, 2001]. In a follow up study
[Miranda-Verastegui et al, 2005], naïve patients were randomized between the combination of
Sb plus imiquimod (18 patients) vs Sb plus placebo (20 patients). The cure rate at 1 month
after therapy was 50% in the imiquimod +Sb group compared to 15% in the placebo+Sb group (p
= 0.02). By 12 months after therapy, the Sb+placebo group had caught up, and the cure rate
was 72%-75% in each group. Local side effects were evaluated. Edema, itching, burning, pain
were equal in the two groups. There was more erythema in the imiquimod grup (55% of
patients) compared to the placebo group (25% of patients).
The Imiquimod studies in neighboring Peru suggest that combination with this immunomodulator
is capable of decreasing the time to cure, and potentially increasing the cure rate, in
Andean cutaneous leishmaniasis. The present study will evaluate the combination of oral
miltefosine plus topical imiquimod for cutaneous leishmaniasis in Bolivia. If in the first
group of patients, cure rate at 1 month after therapy is appreciably above the 70% historic
value for miltefosine alone and the cure rate at 6 months is greater than the 88% historic
value for miltefosine alone, subsequent patients will be randomized between
miltefosine+imiquimod and miltefosine+placebo cream.
Status | Completed |
Enrollment | 60 |
Est. completion date | July 2010 |
Est. primary completion date | March 2010 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 12 Years and older |
Eligibility |
Inclusion Criteria: - Gender: Male or female - Age: >12 yrs of age - Presentation: At least 1 lesion must be ulcerative. No more than 3 lesions. Parasitology: Parasitological confirmation of 1 lesion will be made by visualization or culture of leishmania from the biopsy or aspirate of the lesion. - No specific or putatively specific therapy (Sb, pentamidine, amphotericin B, imidazoles, allopurinol) in the last 6 months Exclusion Criteria: - Previous treatment for leishmaniasis - concomitant diseases by history - abnormal complete blood counts (white blood count, hemoglobin, platelet count), values of liver transaminases (SGOT), kidney function tests (creatinine). - pregnancy or breastfeeding or not willing to take contraception for 3 months after the end of treatment. |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Bolivia | Cenetrop | Santa Cruz | SC |
Lead Sponsor | Collaborator |
---|---|
Foundation Fader |
Bolivia,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Healing of ulcers | 45 days | No | |
Secondary | Clinical findings and normal laboratory parameters | 28 days | Yes |
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