Treatment of Bolivian L Braziliensis Mucosal Leishmaniasis with Inhaled Pentamidine Plus Oral Miltefosine

NCT06550609 | Recruiting Phase 2

• 1 other identifier: ABF-BO-100-10
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2 study of the combination of inhaled-pentamidine plus oral miltefosine for Bolivian mucosal leishmaniasis.

Conditions

Mucosal Leishmaniasis

Keywords

Leishmaniasis; Mucosal leishmaniasis; Miltefosine; Pentamidine; Combined therapy

Outcome Measures

Primary Outcomes (1)

• Efficacy

  Clinical Score.Qualification compromise in five places (nose skin, nose mucosa, mouh-palate mucosa, pharynx and larynx usind four signs ( erythema, inflamation, infiltration and ulceration) with this scale: 0= absen5t, 1=mild, 2= moderate and 3= severe. Maximun score: 60

  25 months

Secondary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  6 months

Study Arms (1)

Subjects treated

EXPERIMENTAL

Miltefosine TID for 28 days Inhaled pentamidine 300 mg on days 1,3,5,8,10,12,15,17,19,22

Drug: Miltefosine Oral Capsule

Interventions

Miltefosine Oral Capsule DRUG

Miltefosine 3 pill per day during 28 days AND pentamidine inhaled 300 mg / d during 10 dosis

Also known as: Pentamidine isethionate inhaled

Subjects treated

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Gender: Male or female
• Age: \>12 yrs of age
• Weight: \> 45 kg
• Consent: Prior to any investigations
• Mucosal disease: Involvement of the nares, nasal mucosa, palate, pharynx, larynx according to the ENT specialist.
• Parasitology: Parasitological confirmation of the lesion (s) will be made by visualization of Leishmania, culture of Leishmania, or molecular identification of Leishmania (PCR) from the biopsy or aspirate of the lesion (s); or a positive Leishmanin skin test plus a scar characteristic of cutaneous leishmaniasis, plus the epidemiologic antecedent of living now or in the past, in an endemic area.

You may not qualify if:

• Previous treatment for leishmaniasis: No specific or putatively specific therapy (Sb, pentamidine, amphotericin B, miltefosine, imidazoles, allopurinol) in the last 12 months. Patients may have been previously treated with the agents under investigation---miltefosine, pentamidine---if that treatment ended more than 12 months ago and the disease has not diminished in the last 6 months.
• Other diseases: Concomitant diseases by history that would be likely in the PI's opinion to interact, either positively or negatively, with treatment.
• Laboratory : Values of complete blood count, liver function (AST, ALT, alkaline phosphatase), renal function (creatinine, BUN), pancreatic function (lipase), or uric acid beyond 1.5 x Normal Range and that in the PI's opinion would be clinically meaningful.
• EKG: Clinically significant abnormalities.
• Contraception: Women of childbearing age are required to practice reproductive contraception for 5 months after initiating therapy: abstinence or effective contraception defined as 2 forms of contraception \[a barrier method (diaphragm, condom, or cervical cap with spermicidal foam, gel, or cream) plus a 2nd barrier method or hormonal contraceptive or intrauterine device\] from day 1 through 5 months post therapy.

Sponsors & Collaborators

• Fundacion Nacional de Dermatologia: lead

Study Sites (1)

Hospital de Clinicas

La Paz, La Paz Department, 00000, Bolivia

RECRUITING

Related Publications (5)

• Aronson N, Herwaldt BL, Libman M, Pearson R, Lopez-Velez R, Weina P, Carvalho E, Ephros M, Jeronimo S, Magill A. Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Am J Trop Med Hyg. 2017 Jan 11;96(1):24-45. doi: 10.4269/ajtmh.16-84256. Epub 2016 Dec 7. No abstract available.

  PMID: 27927991 BACKGROUND

• Carvalho JP, Silva SN, Freire ML, Alves LL, Souza CSA, Cota G. The cure rate after different treatments for mucosal leishmaniasis in the Americas: A systematic review. PLoS Negl Trop Dis. 2022 Nov 17;16(11):e0010931. doi: 10.1371/journal.pntd.0010931. eCollection 2022 Nov.

  PMID: 36395328 BACKGROUND

• Cincura C, de Lima CMF, Machado PRL, Oliveira-Filho J, Glesby MJ, Lessa MM, Carvalho EM. Mucosal leishmaniasis: A Retrospective Study of 327 Cases from an Endemic Area of Leishmania (Viannia) braziliensis. Am J Trop Med Hyg. 2017 Sep;97(3):761-766. doi: 10.4269/ajtmh.16-0349. Epub 2017 Jul 19.

  PMID: 28722607 BACKGROUND

• Piccica M, Lagi F, Bartoloni A, Zammarchi L. Efficacy and safety of pentamidine isethionate for tegumentary and visceral human leishmaniasis: a systematic review. J Travel Med. 2021 Aug 27;28(6):taab065. doi: 10.1093/jtm/taab065.

  PMID: 33890115 BACKGROUND

• Soto J, Toledo J, Valda L, Balderrama M, Rea I, Parra R, Ardiles J, Soto P, Gomez A, Molleda F, Fuentelsaz C, Anders G, Sindermann H, Engel J, Berman J. Treatment of Bolivian mucosal leishmaniasis with miltefosine. Clin Infect Dis. 2007 Feb 1;44(3):350-6. doi: 10.1086/510588. Epub 2006 Dec 27.

  PMID: 17205440 BACKGROUND

MeSH Terms

Conditions

Leishmaniasis, Mucocutaneous; Leishmaniasis

Interventions

miltefosine

Condition Hierarchy (Ancestors)

Leishmaniasis, Cutaneous; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

jaime soto, MD

CONTACT

75648894; Jasm.dlb@gmail.com

Paula Soto, MD

CONTACT

75648893; dra.paula.dermalaser@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This proof-of-concept phase 2 trial will enroll 20 moderate-to-severe ML patients. The primary endpoint is the cure rate for moderate-severe patients in comparison to literature values for miltefosine alone. If mild ML patients present, up to 10 will also be enrolled. The secondary endpoint is demonstrating that the cure rate for mild disease is 90%-100%.

Study Record Dates

• First Submitted: August 8, 2024
• First Posted: August 13, 2024
• Study Start: February 4, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: February 26, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

BO (1)