Ciclosporin in HTLV-1 Associated Myelopathy/ Tropical Spastic Paraparesis (HAM/TSP) (HAM05)

This study has been completed.
Sponsor:
Collaborators:
Medical Research Council
Selly Oak Hospital, Birmingham, UK
St Mary Hospital, Imperial College Healthcare NHS Trust, London, UK
Information provided by (Responsible Party):
Graham Taylor, Imperial College London
ClinicalTrials.gov Identifier:
NCT00773292
First received: October 15, 2008
Last updated: April 12, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
HTLV I Associated Myelopathy
Drug: ciclosporin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The HAM Ciclosporin Study : an Observational Trial of Therapy in Early or Progressing HAM/TSP

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Incidence of clinical failure [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in clinical outcome measures at 12,24, 48 and 72 weeks compared to baseline [ Time Frame: 12, 24, 48 and 72 weeks ] [ Designated as safety issue: No ]

Enrollment: 7
Study Start Date: August 2006
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ciclosporin
48 weeks treatment with ciclosporin
Drug: ciclosporin
Ciclosporin 2.5 - 5mg/kg/day in two equally divided doses. dose adjusted according to trough ciclosporin concentration

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.

  Eligibility

Ages Eligible for Study:   16 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • HIV infection
  • Tuberculosis, strongyloidiasis or other infection related to immune compromise
  • Hepatitis B & C viral infections
  • Malignancy
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00773292

Locations
United Kingdom
National Centre for Human Retrovirology
London, United Kingdom, W2 1NY
Sponsors and Collaborators
Imperial College London
Medical Research Council
Selly Oak Hospital, Birmingham, UK
St Mary Hospital, Imperial College Healthcare NHS Trust, London, UK
Investigators
Principal Investigator: Graham P Taylor Imperial College London
  More Information

No publications provided

Responsible Party: Graham Taylor, Reader in Communicable Diseases, Imperial College London
ClinicalTrials.gov Identifier: NCT00773292     History of Changes
Other Study ID Numbers: Cro423
Study First Received: October 15, 2008
Last Updated: April 12, 2013
Health Authority: United Kingdom: Medicines and Health Devices Regulatory Authority

Keywords provided by Imperial College London:
HAM/TSP

Additional relevant MeSH terms:
Paraparesis, Tropical Spastic
Bone Marrow Diseases
Hematologic Diseases
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
Cyclosporins
Cyclosporine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on October 19, 2014