Effect of Raltegravir in Patients With Acute Tropical Spastic Paraparesis - Human T-Lymphotropic Virus 1 Infection

Tropical Spastic Paraparesis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02655471
• Other study ID #: 65384
• Status: Completed
• Phase: Early Phase 1
• Start date: July 1, 2017
• Est. completion date: March 15, 2019

Study information

• Verified date: May 2019
• Source: Universidad Peruana Cayetano Heredia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 15, 2019
• Est. primary completion date: March 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• HTLV-I Infections
• Infection
• Muscle Spasticity
• Paraparesis
• Paraparesis, Spastic
• Tropical Spastic Paraparesis

Intervention

Drug:
• "Raltegravir" and "Zidovudine"
Through measure of pro-viral load and clinical score, we evaluate about safety and efficacy of combination of Raltegravir 400 mg BID and zidovudine 300 mg BID in patients with recent onset of Tropical Spastic paraparesis due HTLV-1 during 48 weeks

Locations

Country	Name	City	State
Peru	Instituto de Medicina Tropical Alexander von Humboldt	Lima

Sponsors (2)

Lead Sponsor	Collaborator
Universidad Peruana Cayetano Heredia	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Peru, 

References & Publications (10)

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;3 — View 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 I — View Citation

Hermine O, Allard I, Lévy 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. 2 — View 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. — View 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 wit — View 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. — View Citation

Treviño 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. — View Citation

Varrin-Doyer M, Nicolle A, Marignier R, Cavagna S, Benetollo C, Wattel E, Giraudon P. Human T lymphotropic virus type 1 increases T lymphocyte migration by recruiting the cytoskeleton organizer CRMP2. J Immunol. 2012 Feb 1;188(3):1222-33. doi: 10.4049/jim — View Citation

Verdonck K, González 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure of proviral load	Evaluate the effect of raltegravir on proviral load , measured as copies/1000 PBMC, in patients with myelopathy of recent onset associated to HTLV-1 at 48 weeks.	48 weeks
Secondary	Measure of Disability Scale	Evaluate the effect of raltegravir on Kurtzke Expanded Disability Status Scale in patients with myelopathy of recent onset associated to HTLV-1 at 48 weeks.	48 weeks