HTLV-I InfectionEarly Phase 1NCT01867320
Raltegravir for HAM/TSP
A Early Phase 1 study testing Raltegravir in people with HTLV-I Infection, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HTLV-I Infection
- What is being tested?
- Raltegravir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Sep 2013to 25 Sep 2018
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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)
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.
Read more
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.
Read the 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.
- Conditions
- HTLV-I Infection
- Being tested
- Raltegravir
- Keywords
- PVL, Immune, Activation, HTLV-1, HTLV-1 Associated Myelopathy
- Medical subject headings
- HTLV-I Infections, Paraparesis, Tropical Spastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RaltegravirDrug
Raltegravir at 400mg by mouth twice daily in an initial 6 months treatment phase, followed by an additional 9 months post treatment phase.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Raltegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: month 6 compared to pretreatment value
Secondary outcomes (1)
Safety and tolerability of Raltegravir
Safety and tolerability will be assessed at each patient visit by full interim history, physical exam and clinical bloodwork. Neurologic safety will be specifically assessed by Standardized neurologic examination and scoring relevant to HAM/TSP
Measured: each patient visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2013 (estimated)
- Study start5 Sep 2013
- Primary completion25 Sep 2018
- Study completion25 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HTLV-I InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Steven Jacobson, Ph.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01867320
- Sponsor's protocol ID
- 130135
- Other IDs
- 13-N-0135
- Status last verified
- Mar 2023
- First submitted
- 21 May 2013
- Last updated
- 30 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 9859969Asquith 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.
PubMed 11186302Aye 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.
PubMed 10965793Enose-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.
PubMed 34562313
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01867320
- Acronym / sponsor ID
- 130135
- Conditions
- HTLV-I Infection
- Keywords
- PVL, Immune, Activation, HTLV-1, HTLV-1 Associated Myelopathy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 5 Sep 2013 (actual)
- Primary completion
- 25 Sep 2018 (actual)
- Study completion
- 25 Sep 2018 (actual)
- First posted
- 4 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Raltegravir | Experimental | Drug: RaltegravirRaltegravir at 400mg by mouth twice daily in an initial 6 months treatment phase, followed by an additional 9 months post treatment phase. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RaltegravirRaltegravir at 400mg by mouth twice daily in an initial 6 months treatment phase, followed by an additional 9 months post treatment phase. | Drug | Raltegravir |
Primary outcome
HTLV-1 Proviral load, which will be measured by quantitative PCR
Time frame: month 6 compared to pretreatment value
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.
1 secondary outcome
Safety and tolerability of Raltegravir
Time frame: each patient visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2023.
- Background: PubMed 9859969Araujo 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.
- Background: PubMed 11186302Asquith 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.
- Background: PubMed 10965793Aye 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.
- Derived from this study: PubMed 34562313Enose-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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Jacobson, Ph.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Raltegravir in people with HTLV-I Infection, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HTLV-1 Proviral load, which will be measured by quantitative PCR (time frame: month 6 compared to pretreatment value). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01867320, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2023.