Cutaneous LeishmaniasisPhase 2/3GTNCT01464242
Add-on Study of Pentoxifylline in Cutaneous Leishmaniasis
A Phase 2/3 study testing Meglumine antimonate and Pentoxifylline in people with Cutaneous Leishmaniasis, run by Centro Internacional de Entrenamiento e Investigaciones Médicas at 1 site in Colombia.
Trial summary
The purpose of this study is to determine whether adding pentoxifylline to treatment of American cutaneous leishmaniasis with meglumine antimoniate increases the rate and speed of clinical response without diminishing safety, and to identify immune correlates of the healing response. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Cutaneous Leishmaniasis
- What is being tested?
- Meglumine antimonate and Pentoxifylline
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 1 siteColombia
- Study dates
- Nov 2011to Dec 2015
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with clinical diagnosis of cutaneous leishmaniasis (parasitologic confirmation or presumptive biopsy plus a positive Montenegro skin test).
- Age between 18 and 65 years.
- Lesions of a duration equal to or greater than one month
- More than one lesion or single lesion greater than 3 cm in diameter.
- Willingness to participate in the study after being informed through a consent process approved by the institutional ethical review committee
Who cannot join
- Pregnant or lactating women, and women who are planning to conceive during the study or that reject the use of birth control methods.
- Medical conditions that compromise the immune system (HIV infection, neoplasias, diabetes mellitus, autoimmune diseases, or use of corticosteroids, immunomodulators or antineoplastic drugs).
- Medical conditions that preclude the use of antimonials or pentoxifylline (cardiac, renal, hepatic or pancreatic disease or abnormalities).
- Alcohol abuse or use of recreational drugs that interfere with adherence to treatment
- Use of drugs with antileishmanial potential during the previous 13 weeks, including pentavalent antimonials, amphotericin B, miltefosine, and pentamidine
- Use of Theophylline , anticoagulants or antiarrhythmics.
Show all 9Show fewer
- Diffuse or disseminated leishmaniasis.
- Mucosal involvement secondary to Leishmania infection.
- Incapacity to attend the study visits or any other condition that according to the investigator could interfere with adherence to study procedures.
Trial locations and contacts
1 site in 1 country.
Colombia1 site
Corporación Centro Internacional de entrenamiento e Investigaciónes Médicas
Cali, Valle del Cauca Department, 5930
About this study
Official title: Therapeutic Gain of Adding the Immunomodulator Pentoxifylline to the Treatment of Cutaneous Leishmaniasis
The purpose of this study is to determine whether adding pentoxifylline to treatment of American cutaneous leishmaniasis with meglumine antimoniate increases the rate and speed of clinical response without diminishing safety, and to identify immune correlates of the healing response.
Read the detailed description
Failure of first line therapies for cutaneous leishmaniasis is a public health issue. Since pathogenesis of dermal leishmaniasis is mediated by the immune and inflammatory responses, resolution of disease and control of infection are intimately linked to the host response. Several investigations have substantiated "proof of principal" for the therapeutic gain of co-adjuvant immunotherapy. This study will evaluate the efficacy and safety of using pentoxifylline (PTX) as a co-adjuvant in the treatment of cutaneous leishmaniasis with meglumine antimoniate in a randomized, double-blind, controlled trial. One arm will receive meglumine antimoniate and PTX and the other arm will receive meglumine antimoniate plus placebo. Efficacy will be assessed at the end of the treatment, and 5, 7, 13 and 26 weeks after initiation of treatment. Efficacy will be measured as the proportion of patients with definitive cure at 26 weeks after initiation of treatment, and time to healing. Safety will be assessed at the end of treatment with respect to the frequency and severity of adverse events.
Blood samples will be taken to evaluate the effects of PTX invitro and ex vivo on cells of the immune system. Proliferation and secretion of cytokines relevant to the immune and inflammatory responses by peripheral blood mononuclear cells will be measured before and after treatment. Likewise, macrophages will be differentiated from peripheral blood monocytes and infected with a strain of L. panamensis transfected with the luciferase (luc) gene. The investigators will measure the capacity of patient macrophages to kill parasites before and after treatment using a luminometric assay of viable parasite burden. Additionally, the investigators will measure the expression of inducible nitric oxide synthase, an enzyme that is necessary for nitric oxide production, one of the main leishmanicidal mechanisms used by macrophages. The investigators postulate that the use of the co-adjuvant with antimonials will increase the therapeutic response and that indicators predictive of a healing response can be identified by this prospective analysis of the immune response and therapeutic outcome.
- Conditions
- Cutaneous Leishmaniasis
- Being tested
- Meglumine antimonate, Placebo, Pentoxifylline
- Keywords
- Cutaneous Leishmaniasis, pentoxifylline, immunomodulation
- Medical subject headings
- Leishmaniasis, Cutaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Meglumine antimonateDrug
Also called Glucantime ®
Glucantime® 20mg/kg/day IM daily for 20 days
PlaceboDrug
Placebo 400mg orally 3 times a day for 20 days
PentoxifyllineDrug
Pentoxifylline 400mg orally 3 times a day for 20 days
| Study group | Role | What they receive |
|---|---|---|
| Glucantime® + pentoxifylline | Experimental | Glucantime® 20mg/kg/day intramuscular injection (IM) daily for 20 days + pentoxifylline 400mg orally 3 times a day for 20 days. Receives: Drug: Meglumine antimonate; Drug: Pentoxifylline |
| Glucantime® + placebo | Placebo comparator | Glucantime® 20mg/kg/day IM each day for 20 days + placebo 400mg orally 3 times a day for 20 days. Receives: Drug: Meglumine antimonate; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary efficacy outcome: Definitive Cure
Definitive cure, defined as complete re-epithelialization and absence of inflammatory signs in all cutaneous leishmaniasis lesions, and absence of new leishmaniasis lesions
Measured: Participants will be followed up to 26 weeks
Primary safety outcome: Adverse Events
Clinical and laboratory adverse events will be qualified according to the Common Toxicity Criteria for Adverse Effects (CTCAE). All unexpected non serious adverse events will be notified and expected adverse events of moderate or higher category will be reported. All serious adverse events will be reported.
Measured: Participants will be followed up to 26 weeks
Secondary outcomes (4)
In vitro lymphoproliferation
Proliferation of peripheral blood mononuclear cells (PBMCs) after stimulation invitro with L. panamensis antigens will be measured by tritiated thymidine uptake
Measured: Participants will be followed for an average of 20 days
Cytokine secretion by PBMCs
Secretion of a panel of cytokines relevant to the inflammatory and immune responses will be measured in supernatants from PBMCs cultured with L. panamensis antigens using Luminex technology
Measured: Participants will be followed for an average of 20 days
Macrophage leishmanicidal capacity
Macrophages will be differentiated from peripheral blood monocytes and their leishmanicidal capacity will be measured by luminometry after infecton with luciferase-transfected promastigotes.
Measured: Participants will be followed for an average of 20 days
Macrophage inducible nitric oxide synthase (iNOS) expression
Macrophage expression of iNOS after infection will be measured by quantitative real-time Polymerase Chain Reaction (RT-PCR).
Measured: Participants will be followed for an average of 20 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2011 (estimated)
- Study startNov 2011
- Primary completionJan 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cutaneous LeishmaniasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centro Internacional de Entrenamiento e Investigaciones Médicas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nancy C Saravia, PhD, Principal investigator, Centro Internacional de Entrenamiento e Investigación Médica
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01464242
- Sponsor's protocol ID
- 222951928964
- Acronym
- GT
- Status last verified
- Aug 2016
- First submitted
- 24 Oct 2011
- Last updated
- 23 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Castro MDM, Cossio A, Velasco C, Osorio L. Risk factors for therapeutic failure to meglumine antimoniate and miltefosine in adults and children with cutaneous leishmaniasis in Colombia: A cohort study. PLoS Negl Trop Dis. 2017 Apr 5;11(4):e0005515. doi: 10.1371/journal.pntd.0005515. eCollection 2017 Apr.
PubMed 28379954
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Gain of Adding the Immunomodulator Pentoxifylline to the Treatment of Cutaneous Leishmaniasis
- ClinicalTrials.gov ID
- NCT01464242
- Acronym / sponsor ID
- GT / 222951928964
- Conditions
- Cutaneous Leishmaniasis
- Keywords
- Cutaneous Leishmaniasis, pentoxifylline, immunomodulation
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Centro Internacional de Entrenamiento e Investigaciones MédicasUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Jan 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 3 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether adding pentoxifylline to treatment of American cutaneous leishmaniasis with meglumine antimoniate increases the rate and speed of clinical response without diminishing safety, and to identify immune correlates of the healing response.
Detailed description
Failure of first line therapies for cutaneous leishmaniasis is a public health issue. Since pathogenesis of dermal leishmaniasis is mediated by the immune and inflammatory responses, resolution of disease and control of infection are intimately linked to the host response. Several investigations have substantiated "proof of principal" for the therapeutic gain of co-adjuvant immunotherapy. This study will evaluate the efficacy and safety of using pentoxifylline (PTX) as a co-adjuvant in the treatment of cutaneous leishmaniasis with meglumine antimoniate in a randomized, double-blind, controlled trial. One arm will receive meglumine antimoniate and PTX and the other arm will receive meglumine antimoniate plus placebo. Efficacy will be assessed at the end of the treatment, and 5, 7, 13 and 26 weeks after initiation of treatment. Efficacy will be measured as the proportion of patients with definitive cure at 26 weeks after initiation of treatment, and time to healing. Safety will be assessed at the end of treatment with respect to the frequency and severity of adverse events.
Blood samples will be taken to evaluate the effects of PTX invitro and ex vivo on cells of the immune system. Proliferation and secretion of cytokines relevant to the immune and inflammatory responses by peripheral blood mononuclear cells will be measured before and after treatment. Likewise, macrophages will be differentiated from peripheral blood monocytes and infected with a strain of L. panamensis transfected with the luciferase (luc) gene. The investigators will measure the capacity of patient macrophages to kill parasites before and after treatment using a luminometric assay of viable parasite burden. Additionally, the investigators will measure the expression of inducible nitric oxide synthase, an enzyme that is necessary for nitric oxide production, one of the main leishmanicidal mechanisms used by macrophages. The investigators postulate that the use of the co-adjuvant with antimonials will increase the therapeutic response and that indicators predictive of a healing response can be identified by this prospective analysis of the immune response and therapeutic outcome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Glucantime® + pentoxifylline | Experimental | Drug: Meglumine antimonate, Drug: PentoxifyllineGlucantime® 20mg/kg/day intramuscular injection (IM) daily for 20 days + pentoxifylline 400mg orally 3 times a day for 20 days. |
| Glucantime® + placebo | Placebo comparator | Drug: Meglumine antimonate, Drug: PlaceboGlucantime® 20mg/kg/day IM each day for 20 days + placebo 400mg orally 3 times a day for 20 days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with clinical diagnosis of cutaneous leishmaniasis (parasitologic confirmation or presumptive biopsy plus a positive Montenegro skin test).
- Age between 18 and 65 years.
- Lesions of a duration equal to or greater than one month
- More than one lesion or single lesion greater than 3 cm in diameter.
- Willingness to participate in the study after being informed through a consent process approved by the institutional ethical review committee
Key exclusion criteria (9 listed)
- Pregnant or lactating women, and women who are planning to conceive during the study or that reject the use of birth control methods.
- Medical conditions that compromise the immune system (HIV infection, neoplasias, diabetes mellitus, autoimmune diseases, or use of corticosteroids, immunomodulators or antineoplastic drugs).
- Medical conditions that preclude the use of antimonials or pentoxifylline (cardiac, renal, hepatic or pancreatic disease or abnormalities).
- Alcohol abuse or use of recreational drugs that interfere with adherence to treatment
- Use of drugs with antileishmanial potential during the previous 13 weeks, including pentavalent antimonials, amphotericin B, miltefosine, and pentamidine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Meglumine antimonateAlso: Glucantime ®Glucantime® 20mg/kg/day IM daily for 20 days | Drug | Glucantime® + pentoxifylline, Glucantime® + placebo |
| PlaceboPlacebo 400mg orally 3 times a day for 20 days | Drug | Glucantime® + placebo |
| PentoxifyllinePentoxifylline 400mg orally 3 times a day for 20 days | Drug | Glucantime® + pentoxifylline |
Primary outcome
Primary efficacy outcome: Definitive Cure
Time frame: Participants will be followed up to 26 weeks
Definitive cure, defined as complete re-epithelialization and absence of inflammatory signs in all cutaneous leishmaniasis lesions, and absence of new leishmaniasis lesions
Primary safety outcome: Adverse Events
Time frame: Participants will be followed up to 26 weeks
Clinical and laboratory adverse events will be qualified according to the Common Toxicity Criteria for Adverse Effects (CTCAE). All unexpected non serious adverse events will be notified and expected adverse events of moderate or higher category will be reported. All serious adverse events will be reported.
4 secondary outcomes
In vitro lymphoproliferation
Time frame: Participants will be followed for an average of 20 days
Cytokine secretion by PBMCs
Time frame: Participants will be followed for an average of 20 days
Macrophage leishmanicidal capacity
Time frame: Participants will be followed for an average of 20 days
Macrophage inducible nitric oxide synthase (iNOS) expression
Time frame: Participants will be followed for an average of 20 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2016.
- Derived from this study: PubMed 28379954Castro MDM, Cossio A, Velasco C, Osorio L. Risk factors for therapeutic failure to meglumine antimoniate and miltefosine in adults and children with cutaneous leishmaniasis in Colombia: A cohort study. PLoS Negl Trop Dis. 2017 Apr 5;11(4):e0005515. doi: 10.1371/journal.pntd.0005515. eCollection 2017 Apr.
Related trials for Cutaneous Leishmaniasis
RecruitingObservational study
Diagnosis and Treatment of Leishmania Infections
Kinetoplastid, Skin Diseases, Parasitic
Recruiting
Feasibility of Integrating Thermotherapy for Treatment of Cutaneous Leishmaniasis in Primary Health Care Setup
Cutaneous Leishmaniasis
Not yet recruiting
Immersive Technology Headsets to Reduce Procedural Pain and Anxiety: Feasibility and Effects in Cutaneous Leishmaniasis Patients in Pakistan
Cutaneous Leishmaniasis, Pain
RecruitingObservational study
Ex Vivo Immunogenicity Screening of Vaccine Candidate Antigen Combinations in Ethiopian Patients With Leishmaniasis
Leishmaniasis, Cutaneous, Leishmaniasis
Not yet recruitingPhase 2
Comparison of Intralesional Glucantime With and Without Fractional CO₂ Laser in Adults With Cutaneous Leishmaniasis
Cutaneous Leishminiasis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nancy C Saravia, PhD principal investigator
Centro Internacional de Entrenamiento e Investigación Médica
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Meglumine antimonate and Pentoxifylline in people with Cutaneous Leishmaniasis, run by Centro Internacional de Entrenamiento e Investigaciones Médicas at 1 site in Colombia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Colombia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary efficacy outcome: Definitive Cure (time frame: Participants will be followed up to 26 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01464242, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2016.