HTLV I Associated MyelopathyPhase 2/3HAM05NCT00773292
Ciclosporin in HTLV-1 Associated Myelopathy/ Tropical Spastic Paraparesis (HAM/TSP)
A Phase 2/3 study testing ciclosporin in people with HTLV I Associated Myelopathy, run by Imperial College London at 1 site in United Kingdom.
Trial summary
HAM/TSP is a chronic disease of the spinal cord, caused by a virus called HTLV-I. Worldwide approximately 20 million persons are infected.Infection with HTLV-I is lifelong, and about 3% of infected persons will develop this chronic debilitating disease, of which half will become wheelchair dependent. Read more about this study
- Who is it for?
- Ages 16 to 75 years
- Conditions the study is for
- HTLV I Associated Myelopathy
- What is being tested?
- ciclosporin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2006to Jan 2010
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 16 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Early (less than 2 years) HAM
- Progressing (within past 3 months) HAM
- Important to study the effect of therapy on disease that is most active as most likely to detect and measure improvement
Who cannot join
- HIV infection
- Tuberculosis, strongyloidiasis or other infection related to immune compromise
- Hepatitis B \& C viral infections
- Malignancy
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
National Centre for Human Retrovirology
London, W2 1NY
About this study
Official title: The HAM Ciclosporin Study : an Observational Trial of Therapy in Early or Progressing HAM/TSP
HAM/TSP is a chronic disease of the spinal cord, caused by a virus called HTLV-I. Worldwide approximately 20 million persons are infected.Infection with HTLV-I is lifelong, and about 3% of infected persons will develop this chronic debilitating disease, of which half will become wheelchair dependent. We, and others, have shown a strong and persistent immune response to HTLV-I in carriers and patients with HAM/TSP, but this fails to clear the virus. However, carriers with a low burden of virus in the blood have a low risk of developing disease. The immune response in these carriers seems better able to kill infected cells. A less efficient response is associated with a higher viral burden that drives the immune response with a resultant release of chemicals by the immune cells that inadvertently cause harm, most especially to cells in the spinal cord. Our understanding of HAM/TSP suggests that targeting the immune response should improve the health of our patients especially if the disease is diagnosed early. To identify the best type of treatment we are planning a series of studies of drugs that target the immune response in different ways. Each has been used in other inflammatory conditions but never before studied in HAM/TSP. We aim to study the extent and duration of the clinical response and to associate this with the different effects that the therapies have on the immune response and on the number of HTLV-I infected cells in the blood. This in turn will improve our knowledge and understanding of the disease and should lead to better therapy. This application is in relation to the first study - to explore that therapeutic benefit of ciclosporin in patients with HAM/TSP.
Read the detailed description
This is a proof of concept, open, observational study of Ciclosporin for the treatment of HTLV-I-associated myelopathy in patients with less than 2 years disease or new evidence of progression. After two baseline assessments patients will be commenced on ciclosporin in a weight dependent dose (2.5 - 5mg/kg/day) and the dose adjusted according to plasma drug concentrations. Participants will be monitored on a further 11 occasion as per the schedule every 2 - 8 weeks (less frequent with time) by self-administered questionnaires relating to quality of life and spasticity, by regular assessment of pain, timed walk, spasticity, bladder and bowel function and by blood tests to ensure the safety of the therapy. Blood samples will also be collected, at the same time points, for investigation of the immune response to HTLV-I and the quantity and activity of the virus. At 5 key time points the participants will undergo a more detailed neurological examination, the spinal cord will be imaged by MRI before, once during (12 weeks) and at the completion of the study and the fluid that bathes the brain (CSF) will be examined before and after 12 weeks of therapy. Therapy is planned for 12 months with 6 months further follow-up but therapy will be continued or discontinued according to clinical response.
- Conditions
- HTLV I Associated Myelopathy
- Being tested
- ciclosporin
- Keywords
- HAM/TSP
- Medical subject headings
- Paraparesis, Tropical Spastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ciclosporinDrug
Ciclosporin 2.5 - 5mg/kg/day in two equally divided doses. dose adjusted according to trough ciclosporin concentration
| Study group | Role | What they receive |
|---|---|---|
| ciclosporin | Experimental | 48 weeks treatment with ciclosporin Receives: Drug: ciclosporin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patient With Lack of Objective Clinical Improvement
Lack of objective clinical improvement after three months of therapy. Objective improvement was defined as any of the following comparing baseline measurements to 12, 24 and 48 weeks: i) one point decrease in the IPEC 1 scale (Instituto de Pesquisa Clínica Evandro Chagas), ii) >30% improvement in 10 m timed walk, iii) visual analogue pain score reduced by >2 points, iv) reduction of frequency or nocturia by greater than one or reduction of residual volume by more than 10% at two consecutive visits.
Proof of concept study and therefore outcomes report is descriptive only. No statistical test appropriate.
Measured: up to 12 months
Secondary outcomes (1)
Change in Timed Walk Rank Between Baseline and 12 Weeks
Change in the time taken to walk 10 meters 0 - 12 weeks compared with baseline. A timed walk rank was created to take into account the use of walking aids.
Timed walk rank was calculated by ranking the time to walk 10 meters over all patients and visits, in the following order (highest/worst score to lowest/best score): unable to walk; able to walk, but not able to complete 10 meters (ranked on distance walked and time taken); able to walk 10 meters with a bilateral aid; able to walk 10 meters with a unilateral aid; able to walk 10 meters unaided (all ranked on time taken).
Decrease in score means improvement. All evaluable patients were ranked on the time taken. There is no specific range for the rank scores. Upper and lower limits vary with the number of participants evaluated
Measured: 0, 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2008 (estimated)
- Study startAug 2006
- Primary completionJan 2010
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HTLV I Associated MyelopathyStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- 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
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council, University Hospital Birmingham, Imperial College Healthcare NHS Trust
- Responsible party
- Sponsor
- Investigators
- Graham P Taylor, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00773292
- Sponsor's protocol ID
- Cro423
- Acronym
- HAM05
- Status last verified
- Sep 2021
- First submitted
- 15 Oct 2008
- Last updated
- 9 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Martin F, Castro H, Gabriel C, Adonis A, Fedina A, Harrison L, Brodnicki L, Demontis MA, Babiker AG, Weber JN, Bangham CR, Taylor GP. Ciclosporin A proof of concept study in patients with active, progressive HTLV-1 associated myelopathy/tropical spastic paraparesis. PLoS Negl Trop Dis. 2012;6(6):e1675. doi: 10.1371/journal.pntd.0001675. Epub 2012 Jun 12.
PubMed 22720101
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The HAM Ciclosporin Study : an Observational Trial of Therapy in Early or Progressing HAM/TSP
- ClinicalTrials.gov ID
- NCT00773292
- Acronym / sponsor ID
- HAM05 / Cro423
- Conditions
- HTLV I Associated Myelopathy
- Keywords
- HAM/TSP
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Medical Research Council, University Hospital Birmingham, Imperial College Healthcare NHS Trust
- Study start
- Aug 2006
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 16 Oct 2008 (estimated)
- Results
- Posted 9 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
HAM/TSP is a chronic disease of the spinal cord, caused by a virus called HTLV-I. Worldwide approximately 20 million persons are infected.Infection with HTLV-I is lifelong, and about 3% of infected persons will develop this chronic debilitating disease, of which half will become wheelchair dependent. We, and others, have shown a strong and persistent immune response to HTLV-I in carriers and patients with HAM/TSP, but this fails to clear the virus. However, carriers with a low burden of virus in the blood have a low risk of developing disease. The immune response in these carriers seems better able to kill infected cells. A less efficient response is associated with a higher viral burden that drives the immune response with a resultant release of chemicals by the immune cells that inadvertently cause harm, most especially to cells in the spinal cord. Our understanding of HAM/TSP suggests that targeting the immune response should improve the health of our patients especially if the disease is diagnosed early. To identify the best type of treatment we are planning a series of studies of drugs that target the immune response in different ways. Each has been used in other inflammatory conditions but never before studied in HAM/TSP. We aim to study the extent and duration of the clinical response and to associate this with the different effects that the therapies have on the immune response and on the number of HTLV-I infected cells in the blood. This in turn will improve our knowledge and understanding of the disease and should lead to better therapy. This application is in relation to the first study - to explore that therapeutic benefit of ciclosporin in patients with HAM/TSP.
Detailed description
This is a proof of concept, open, observational study of Ciclosporin for the treatment of HTLV-I-associated myelopathy in patients with less than 2 years disease or new evidence of progression. After two baseline assessments patients will be commenced on ciclosporin in a weight dependent dose (2.5 - 5mg/kg/day) and the dose adjusted according to plasma drug concentrations. Participants will be monitored on a further 11 occasion as per the schedule every 2 - 8 weeks (less frequent with time) by self-administered questionnaires relating to quality of life and spasticity, by regular assessment of pain, timed walk, spasticity, bladder and bowel function and by blood tests to ensure the safety of the therapy. Blood samples will also be collected, at the same time points, for investigation of the immune response to HTLV-I and the quantity and activity of the virus. At 5 key time points the participants will undergo a more detailed neurological examination, the spinal cord will be imaged by MRI before, once during (12 weeks) and at the completion of the study and the fluid that bathes the brain (CSF) will be examined before and after 12 weeks of therapy. Therapy is planned for 12 months with 6 months further follow-up but therapy will be continued or discontinued according to clinical response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ciclosporin | Experimental | Drug: ciclosporin48 weeks treatment with ciclosporin |
Who may qualify
- Ages
- 16 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Early (less than 2 years) HAM
- Progressing (within past 3 months) HAM
- Important to study the effect of therapy on disease that is most active as most likely to detect and measure improvement
Key exclusion criteria (4 listed)
- HIV infection
- Tuberculosis, strongyloidiasis or other infection related to immune compromise
- Hepatitis B \& C viral infections
- Malignancy
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 |
|---|---|---|
| ciclosporinCiclosporin 2.5 - 5mg/kg/day in two equally divided doses. dose adjusted according to trough ciclosporin concentration | Drug | ciclosporin |
Primary outcome
Number of Patient With Lack of Objective Clinical Improvement
Time frame: up to 12 months
Lack of objective clinical improvement after three months of therapy. Objective improvement was defined as any of the following comparing baseline measurements to 12, 24 and 48 weeks: i) one point decrease in the IPEC 1 scale (Instituto de Pesquisa Clínica Evandro Chagas), ii) >30% improvement in 10 m timed walk, iii) visual analogue pain score reduced by >2 points, iv) reduction of frequency or nocturia by greater than one or reduction of residual volume by more than 10% at two consecutive visits. Proof of concept study and therefore outcomes report is descriptive only. No statistical test appropriate.
1 secondary outcome
Change in Timed Walk Rank Between Baseline and 12 Weeks
Time frame: 0, 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22720101Martin F, Castro H, Gabriel C, Adonis A, Fedina A, Harrison L, Brodnicki L, Demontis MA, Babiker AG, Weber JN, Bangham CR, Taylor GP. Ciclosporin A proof of concept study in patients with active, progressive HTLV-1 associated myelopathy/tropical spastic paraparesis. PLoS Negl Trop Dis. 2012;6(6):e1675. doi: 10.1371/journal.pntd.0001675. Epub 2012 Jun 12.
- Individual participant dataSharing planned: No
Related trials for HTLV I Associated Myelopathy
RecruitingObservational study
Evaluation of Patients With HAM/TSP
HTLV-I Infection, Tropical Spastic Paraparesis
RecruitingPhase 1/2
Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
HAM/TSP
RecruitingPhase 2
Dolutegravir Versus Dolutegravir in Combination With Tenofovir for the Treatment of HTLV-1 Infection
HTLV-1 Infection, HTLV I Associated Myelopathies
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.
Graham P Taylor principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing ciclosporin in people with HTLV I Associated Myelopathy, run by Imperial College London at 1 site in United Kingdom.
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 3 inclusion and 4 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 9 Sep 2021. 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 Kingdom. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Patient With Lack of Objective Clinical Improvement (time frame: up to 12 months). 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 NCT00773292, which also lists 1 linked publication.
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 9 Sep 2021.