Ciclosporin in HTLV-1 Associated Myelopathy/ Tropical Spastic Paraparesis (HAM/TSP)
Condition: HTLV I Associated Myelopathy
MeSH terms: Paraparesis, Tropical Spastic; Spinal Cord Diseases; Bone Marrow Diseases
Study type: Interventional
Phase: Phase 2/Phase 3

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. 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.
    

Intervention name(s): ciclosporin
Intervention type(s): Drug
Intervention description(s): Ciclosporin 2.5 - 5mg/kg/day in two equally divided doses. dose adjusted according to trough ciclosporin concentration
Intervention MeSH terms: Cyclosporine; Cyclosporins
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HAM/TSP