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

NCT02655471 | Completed Early Phase 1 FDA Drug

• 1 other identifier: 65384
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

HTLV-I Infections; Tropical Spastic Paraparesis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Measure of Disability Scale

  48 weeks

Study Arms (1)

HTLV-1 plus Tropical Spastic paraparesis

EXPERIMENTAL

Patients with recent onset of Tropical Spastic paraparesis due HTLV-1 will receive combination of "Raltegravir" and "Zidovudine" during 48 weeks

Drug: "Raltegravir" and "Zidovudine"

Interventions

"Raltegravir" and "Zidovudine" DRUG

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

Also known as: "Raltegravir", "Zidovudine"

HTLV-1 plus Tropical Spastic paraparesis

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universidad Peruana Cayetano Heredia: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Instituto de Medicina Tropical Alexander von Humboldt

Lima, 01, Peru

Location

Related Publications (10)

• 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.

  PMID: 17376384 RESULT

• 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.

  PMID: 9180608 RESULT

• 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.

  PMID: 19578703 RESULT

• 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.

  PMID: 20573027 RESULT

• 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/jimmunol.1101562. Epub 2012 Jan 6.

  PMID: 22227566 RESULT

• 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.

  PMID: 7760890 RESULT

• 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.

  PMID: 12522449 RESULT

• 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.

  PMID: 21343468 RESULT

• 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.

  PMID: 21965433 RESULT

• 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.

  PMID: 15472843 RESULT

MeSH Terms

Conditions

HTLV-I Infections; Paraparesis, Tropical Spastic

Interventions

Raltegravir Potassium; Zidovudine

Condition Hierarchy (Ancestors)

Deltaretrovirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Myelitis; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Eduardo Gotuzzo, MD

  Instituto de Medicina Tropical Alexander von Humboldt

  PRINCIPAL INVESTIGATOR

• Fernando Mejía, MD

  Instituto de Medicina Tropical Alexander von Humboldt

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2015
• First Posted: January 14, 2016
• Study Start: July 1, 2017
• Primary Completion: March 15, 2019
• Study Completion: March 15, 2019
• Last Updated: May 22, 2019

Record last verified: 2019-05

Locations

PE (1)