Clinical trial NCT02655471: Effect of Raltegravir in Patients With Acute Tropical Spastic Paraparesis - Human T-Lymphotropic Virus 1 Infection
Official title: Effect of Raltegravir in Patients With Myelopathy/Tropical Spastic Paraparesis Associated With Infection by Human T-Lymphotropic Virus 1 (HTLV-1). Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: HTLV-I Infections
Tropical Spastic Paraparesis
Lead sponsor: Universidad Peruana Cayetano Heredia
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-01-14
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a pilot study of intervention in a group of patients with tropical spastic paraparesis/ myelopathy to evaluate virologic and clinical response of raltegravir plus zidovudine in this group of patients.

Detailed description: The study will the investigators develop in The Tropical Medicine Institute Alexander von Humboldt that is a referral center in Peru for diseases associated to Human T-Lymphotropic Virus 1 Infection (HTLV-1). The Institute has a cohort of around 600 patients currently being followed up and around 20 to 25 new patients are admitted every year with this disease.

This is a pilot study of intervention in a group of patients with tropical spastic paraparesis/ myelopathy to evaluate virologic and clinical response of raltegravir plus zidovudine in this group of patients on the follow-up of 48 weeks.

Eligibility criteria: Inclusion Criteria:

* human t lymphotrophic virus 1 confirmed
* Tropical Spastic Paraparesis of recent onset (less than 4 years)

Exclusion Criteria:

* Pregnant or breastfeeding or unwilling to use contraception.
* Treatment with immunosuppressive, immunomodulatory or experimental treatments within the last 6 months of enrolment in the study.
* Patients presenting with medical disorder such as poorly controlled diabetes or arterial hypertension, severe cardiac insufficiency, unstable ischemic heart disease, abnormal liver function tests (\>2.5 times upper limit normal (ULN)) and abnormal complete blood count (in particular leukopenia, as defined by a lymphocyte count \<500, neutrophil \<1.5 or platelet count \< 100, or thrombocytopenia \< 1.5 low limit normal (LLN), or any medical condition which, in the opinion of the chief investigator, would pose additional risk to the patient.
* Presence of human immunodeficiency virus antibodies.
* Patients with active hepatitis B or/and C with liver function tests \>2.5 times ULN
* Exposure to any other investigational drug within 30 days of enrolment in the study.

Primary outcomes:
measure: Measure of proviral load
timeFrame: 48 weeks
Secondary outcomes:
measure: Measure of Disability Scale
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Lima
country: Peru
facility: Instituto de Medicina Tropical Alexander von Humboldt
Study officials:
affiliation: Instituto de Medicina Tropical Alexander von Humboldt
name: Eduardo Gotuzzo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto de Medicina Tropical Alexander von Humboldt
name: Fernando Mejía, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Verdonck K, Gonzalez E, Van Dooren S, Vandamme AM, Vanham G, Gotuzzo E. Human T-lymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infect Dis. 2007 Apr;7(4):266-81. doi: 10.1016/S1473-3099(07)70081-6.
citation: Zurita S, Costa C, Watts D, Indacochea S, Campos P, Sanchez J, Gotuzzo E. Prevalence of human retroviral infection in Quillabamba and Cuzco, Peru: a new endemic area for human T cell lymphotropic virus type 1. Am J Trop Med Hyg. 1997 May;56(5):561-5. doi: 10.4269/ajtmh.1997.56.561.
citation: Primo J, Siqueira I, Nascimento MC, Oliveira MF, Farre L, Carvalho EM, Bittencourt AL. High HTLV-1 proviral load, a marker for HTLV-1 associated myelopathy/tropical spastic paraparesis, is also detected in patients with infective dermatitis associated with HTLV-1. Braz J Med Biol Res. 2009 Aug;42(8):761-4. doi: 10.1590/s0100-879x2009005000008. Epub 2009 Jul 3.
citation: Izumo S. Neuropathology of HTLV-1-associated myelopathy (HAM/TSP): The 50th Anniversary of Japanese Society of Neuropathology. Neuropathology. 2010 Oct;30(5):480-5. doi: 10.1111/j.1440-1789.2010.01135.x.
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citation: Gill PS, Harrington W Jr, Kaplan MH, Ribeiro RC, Bennett JM, Liebman HA, Bernstein-Singer M, Espina BM, Cabral L, Allen S, et al. Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine. N Engl J Med. 1995 Jun 29;332(26):1744-8. doi: 10.1056/NEJM199506293322603.
citation: Hermine O, Allard I, Levy V, Arnulf B, Gessain A, Bazarbachi A; French ATL therapy group. A prospective phase II clinical trial with the use of zidovudine and interferon-alpha in the acute and lymphoma forms of adult T-cell leukemia/lymphoma. Hematol J. 2002;3(6):276-82. doi: 10.1038/sj.thj.6200195.
citation: Seegulam ME, Ratner L. Integrase inhibitors effective against human T-cell leukemia virus type 1. Antimicrob Agents Chemother. 2011 May;55(5):2011-7. doi: 10.1128/AAC.01413-10. Epub 2011 Feb 22.
citation: Trevino A, Parra P, Bar-Magen T, Garrido C, de Mendoza C, Soriano V. Antiviral effect of raltegravir on HTLV-1 carriers. J Antimicrob Chemother. 2012 Jan;67(1):218-21. doi: 10.1093/jac/dkr404. Epub 2011 Sep 29.
citation: Gotuzzo E, Cabrera J, Deza L, Verdonck K, Vandamme AM, Cairampoma R, Vizcarra D, Cabada M, Narvarte G, De las Casas C. Clinical characteristics of patients in Peru with human T cell lymphotropic virus type 1-associated tropical spastic paraparesis. Clin Infect Dis. 2004 Oct 1;39(7):939-44. doi: 10.1086/423957. Epub 2004 Sep 1.