Raltegravir for HAM/TSP

NCT01867320 | Completed Early Phase 1

• 2 other identifiers: 13013513-N-0135
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HTLV-I Infection

Keywords

PVL; Immune; Activation; HTLV-1; HTLV-1 Associated Myelopathy

Outcome Measures

Primary Outcomes (1)

• HTLV-1 Proviral load, which will be measured by quantitative PCR

  The primary outcome measure is HTLV-1 proviral load in the peripheral blood mononuclear cells (PBMCs) measured by Taqman at month 6 compared to pretreatment value.

  month 6 compared to pretreatment value

Secondary Outcomes (1)

• Safety and tolerability of Raltegravir

  each patient visit

Study Arms (1)

Raltegravir

EXPERIMENTAL

Raltegravir at 400mg by mouth twice daily in an initial 6 months treatment phase, followed by an additional 9 months post treatment phase.

Drug: Raltegravir

Interventions

Raltegravir DRUG

Raltegravir at 400mg by mouth twice daily in an initial 6 months treatment phase, followed by an additional 9 months post treatment phase.

Raltegravir

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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 3 xULN and confirmed on repeat testing in 2 weeks.
• Platelet count \< 75,000/mm(3)
• Serum creatinine level \> 2.0 mg/dl

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Araujo AQ, Andrade-Filho AS, Castro-Costa CM, Menna-Barreto M, Almeida SM. HTLV-I-associated myelopathy/tropical spastic paraparesis in Brazil: a nationwide survey. HAM/TSP Brazilian Study Group. J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Dec 15;19(5):536-41. doi: 10.1097/00042560-199812150-00014.

  PMID: 9859969 BACKGROUND

• Asquith B, Hanon E, Taylor GP, Bangham CR. Is human T-cell lymphotropic virus type I really silent? Philos Trans R Soc Lond B Biol Sci. 2000 Aug 29;355(1400):1013-9. doi: 10.1098/rstb.2000.0638.

  PMID: 11186302 BACKGROUND

• Aye MM, Matsuoka E, Moritoyo T, Umehara F, Suehara M, Hokezu Y, Yamanaka H, Isashiki Y, Osame M, Izumo S. Histopathological analysis of four autopsy cases of HTLV-I-associated myelopathy/tropical spastic paraparesis: inflammatory changes occur simultaneously in the entire central nervous system. Acta Neuropathol. 2000 Sep;100(3):245-52. doi: 10.1007/s004019900170.

  PMID: 10965793 BACKGROUND

• Enose-Akahata Y, Billioux BJ, Azodi S, Dwyer J, Vellucci A, Ngouth N, Nozuma S, Massoud R, Cortese I, Ohayon J, Jacobson S. Clinical trial of raltegravir, an integrase inhibitor, in HAM/TSP. Ann Clin Transl Neurol. 2021 Oct;8(10):1970-1985. doi: 10.1002/acn3.51437. Epub 2021 Sep 25.

  PMID: 34562313 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

HTLV-I Infections; Paraparesis, Tropical Spastic

Interventions

Raltegravir Potassium

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

Study Officials

• Steven Jacobson, Ph.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 21, 2013
• First Posted: June 4, 2013
• Study Start: September 5, 2013
• Primary Completion: September 25, 2018
• Study Completion: September 25, 2018
• Last Updated: March 30, 2023

Record last verified: 2023-03

Locations

US (1)