The Safety and Cost-effectiveness of Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS): a Randomized Rater-blinded Multicenter Trial.
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Clinical relapses
研究概览
简要总结
The aim of this study is to identify whether it is possible to safely discontinue treatment in relapsing-onset MS patients who have shown no evidence of active inflammation in the years prior to inclusion clinically and/or radiologically. The secondary objectives address the questions whether the discontinuation of first-line treatment has an effect on disability progression and whether the discontinuation of first-line treatment improves the quality of life for the patient. Furthermore, blood collections will be included to assess whether it is possible to retrospectively predict possible return of inflammatory activity with biomarkers such as neurofilament light (NFL) or patient characteristics such as disease activity prior to disease modifying therapy (DMT). In case of emerging disease activity after the cessation of therapy we will assess if reinitiation will lead to NEDA again, and if there are long-term consequences. If possible, post-hoc analysis are performed for the different types of treatment compounds.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Minimum age of 18 years
- •Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local privacy regulations.
- •Definite diagnosis of relapsing-onset MS according to the revised McDonald 2017 criteria
- •Treatment with one of the first-line DMTs: any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide
- •Complete absence of inflammatory activity (no objectively defined and confirmed relapses, no significant number (2 or more) of new-T2 lesions and no contrast-enhancing lesions) for 5 consecutive years under first-line treatment
排除标准
- •A switch between first-line disease modifying therapy over two years prior to inclusion, in case the switch has been due to in effectivity of the first DMT.
- •Women who want to discontinue medication because of a pregnancy wish and women who are pregnant or expect to become pregnant during the study period
- •Patients that have previously used interferon-beta and have been tested positive for neutralizing antibodies (NAbs).
研究组 & 干预措施
Discontinuation of DMT
Discontinuation of first-line disease modifying therapy (any of the interferons, glatiramer acetate, dimethylfumarate, teriflunomide)
干预措施: DMT (Drug)
结局指标
主要结局
Clinical relapses
时间窗: 2 years
New clinically confirmed relapses (defined according to the definition most often used in MS phase-III trials: the onset of new or recurrent symptoms that last \> 24 hours, that are accompanied by new objective abnormalities on a neurological examination and that are not explained by non-MS processes such as fever, infection, severe stress or drug toxicity).
New lesions on MRI-brain
时间窗: 2 years
New inflammatory disease activity on MRI (defined as 3 or more lesions on T2-weighted vimages or 2 or more gadolinium enhancing lesions on T1-weighted post-contrast MRI).
次要结局
- EDSS (Expanded Disability Status Scale)(2 years)
- 9-hole peg test(2 years)
- Timed 25-Foot Walk(2 years)
- Symbol Digits Modalities Test(2 years)
- MRI-parameter: T1 post-contrast lesion number(2 years)
- MRI-parameter: T2 post-contrast lesion number(2 years)
- Multiple Sclerosis Impact Scale (MSIS-29)(2 years)
- Short Form health survey (SF-36)(2 years)
- Checklist Individual Strength (CIS20r)(2 years)
- Treatment Satisfaction Questionnaire for Medication (TSQM)(2 years)
- EuroQol 5 dimensions questionnaire (EQ-5D-5L)(2 years)
- Medical consumption questionnaire (iMCQ)(2 years)
- Productivity costs questionnaire (iPCQ)(2 years)
- Neurofilament light level in serum(2 years)
研究者
Eline Coerver
Corresponding investigator, (also: E.M.M. Strijbis (coordinating investigator) and J. Killestein (principal investigator))
Amsterdam UMC, location VUmc