The HAM Ciclosporin Study : an Observational Trial of Therapy in Early or Progressing HAM/TSP
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Number of Patient With Lack of Objective Clinical Improvement
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •HIV infection
- •Tuberculosis, strongyloidiasis or other infection related to immune compromise
- •Hepatitis B & C viral infections
- •Malignancy
研究组 & 干预措施
ciclosporin
48 weeks treatment with ciclosporin
干预措施: ciclosporin (Drug)
结局指标
主要结局
Number of Patient With Lack of Objective Clinical Improvement
时间窗: 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.
次要结局
- Change in Timed Walk Rank Between Baseline and 12 Weeks(0, 12 weeks)