Trial record 9 of 17 for:    Tropical Spastic Paraparesis

Raltegravir for HAM/TSP

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier:
NCT01867320
First received: May 21, 2013
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

Background:

- Human T-cell lymphotropic virus type 1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an infection of the spinal cord. The infection is caused by a virus that has been known to cause cancers like leukemia and lymphoma. It causes a weakening of the legs. Researchers want to see if raltegravir, a drug for treating human immunodeficiency virus (HIV), can be used to treat HAM/TSP. They will see if the drug can reduce the amount of virus in the blood of people with HAM/TSP.

Objectives:

- To see if raltegravir can reduce the viral load of people with HAM/TSP.

Eligibility:

- Individuals at least 18 years of age who have HAM/TSP.

Design:

  • Participants will be screened with a physical exam and medical history. Blood samples will be collected. Imaging studies will be performed. A lumbar puncture will also be taken.
  • Participants will take the study drug twice a day for 6 months. They will note each dose in a study diary, as well as any side effects.
  • At the 6-month visit, participants will stop taking the study drug. They will have a physical exam and blood samples, as well as other tests.
  • Participants will have two further exams 9 months and 15 months after starting the study drug. They will have a physical exam and blood samples, as well as other tests.

Condition Intervention Phase
HAM/TSP
HTLV-1
Drug: Raltegravir
Phase 0

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Raltegravir, an Integrase Inhibitor, in Human T-Cell Lymphotrophic Virus-1(HTLV-1) Associated Myelopathy, Tropical Spastic Paraparesis (HAM/TSP)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Determine the effect of Raltegravir on HTLV-1 Proviral load in HAM/TSP patients [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 22
Study Start Date: May 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Raltegravir
    N/A
Detailed Description:

Objective:

In this pilot study, we wish to determine the effects of Raltegravir, a clinically approved HIV-1 integrase inhibitor, on HTLV-1 proviral load (PVL) in patients with HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP). We will also provide safety and tolerability information on Raltegravir use in this condition and examine the correlation of immune activation markers in HAM/TSP with the effects of Raltegravir on the PVL.

Study population:

HAM/TSP, a relentlessly progressive and disabling myelopathy, occurs in up to 3% of HTLV-1 infected subjects. It results from immune-mediated bystander damage of the neural tissues in association with an elevated PVL. In fact, a high PVL is considered to be the main risk factor for developing HAM/TSP as the risk of disease rises exponentially once the PVL exceeds 1 %. Currently there is no effective treatment for HAM/TSP.

There is evidence that active HTLV-1 replication, through the retroviral life cycle with new virus integration, is occurring in vivo and contributes to the total HTLV-1 PVL in infected subjects. Recently it was shown that Raltegravir could inhibit cell-free and cell-to-cell transmission of HTLV-1 in vitro. Given the substantial clinical experience with its use in HIV-1 infection and particularly its excellent safety profile, this agent is an attractive therapeutic option for patients with HAM/TSP, either alone or in combination with immunomodulatory treatment. In this pilot study we wish to determine the effects of Raltegravir in vivo on HTLV-1 PVL and immune activation markers in patients with HAM/TSP.

Design:

In this 15 months single center, single arm, open label, baseline versus treatment pilot clinical trial, sixteen subjects with HAM/TSP will receive Raltegravir at 400mg by mouth twice daily in an initial 6 months treatment phase, followed by an additional 9 months post treatment phase. Outcome measures will be collected every 3 months for the duration of the study.

Outcome measures:

The primary outcome measure is HTLV-1 proviral load, which will be measured by quantitative PCR. Secondary outcome measures include safety and tolerability of Raltegravir, which will be assessed by clinical exam and standardized neurological disability scales as well as clinical laboratory studies. In addition, viral and immunologic outcome measures investigating the impact of Raltegravir on HTLV-1 biology and its effects on immune function will be measured including HTLV-1 proviral load in different lymphocyte populations, the number of long terminal repeat (LTR) circles and HTLV-1 mRNA expression levels in freshly isolated PBMC, assays of spontaneous lymphoproliferation and T-cell phenotype analysis.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • 18 years or older
  • Diagnosis of HAM/TSP as defined by WHO criteria, including a positive HTLV-1 EIA and confirmatory Western Blot.
  • Patient must be willing and able to comply with all the aspects of trial design and follow-up.
  • Patients must be able to provide informed consent
  • If able to become pregnant or to father a child, agreeing to commit to the use of a reliable/accepted method of birth control (i.e. hormonal contraception (birth control pills, injected hormones, vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or surgical sterilization (hysterectomy, tubal ligation, or vasectomy) for the duration of treatment arm of the study

EXCLUSION CRITERIA:

  • Alternative diagnoses that can explain neurological disability
  • Clinically significant medical disorders that, in the judgment of the investigators might expose the patient to undue risk of harm confound study outcomes or prevent the patient from completing the study. Examples of such conditions include but are not limited to poorly controlled cardiopulmonary conditions such as congestive heart failure, asthma or uncontrolled hypertension.
  • Patient has received immunomodulatory/immunosuppressive therapy (including steroids) in the preceding 6 months.
  • Patient with known myopathy or risk factors for CK elevation including being on other drugs known to cause myopathy or rhabdomyolysis.
  • Pregnant or lactating women.
  • Patient has received other investigational drugs within 6 months before enrollment
  • Positive serological evidence of HIV, HTLV-II, Hepatitis B or C.
  • Abnormal screening/baseline blood tests exceeding any of the limits defined below:

    • Serum alanine transaminase (ALT) or aspartate transaminase (AST) levels greater than 3 times the upper limit of normal values; total bilirubin > 2.0mg/dl; Serum amylase or lipase levels greater than twice the upper limit of normal values; serum creatine phosphokinase (CK) level exceeding twice the upper limit of normal.
    • ANC < 1,000/mm(3)
    • Platelet count < 75,000/mm(3)
    • Serum creatinine level > 2.0 mg/dl
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01867320

Contacts
Contact: Steven Jacobson, Ph.D. (301) 496-0519 jacobsons@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Steven Jacobson, Ph.D. National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier: NCT01867320     History of Changes
Other Study ID Numbers: 130135, 13-N-0135
Study First Received: May 21, 2013
Last Updated: March 19, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
HTLV-1
HTLV-1 Associated Myelopathy

Additional relevant MeSH terms:
Paraparesis, Tropical Spastic
Myelitis
Central Nervous System Viral Diseases
Virus Diseases
HTLV-I Infections
Deltaretrovirus Infections
Retroviridae Infections
RNA Virus Infections
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Spinal Cord Diseases
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014