The safety and cost-effectiveness of discontinuing disease-modifying therapies in stable relapsing-onset multiple sclerosis (DOT-MS): a randomized rater-blinded multicenter trial.
- Conditions
- multiple sclerosis10012303
- Registration Number
- NL-OMON56344
- Lead Sponsor
- Vrije Universiteit Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Suspended
- Sex
- Not specified
- Target Recruitment
- 130
Patients who are treated with one of the first-line treatments (any of the
interferons, glatiramer acetate, dimethylfumarate, teriflunomide) and who had a
complete absence of inflammatory activity (no relapses, no new-T2 lesions and
no contrast-enhancing lesions on MRI) for 5 consecutive years under first-line
treatment will be eligible for inclusion. In case the last available MRI-scan
was conducted 10 or more years ago, no more than 3 new T2-lesions in these 10
years are accepted.
- Clinical or radiological inflammatory disease activity in the 5 years prior
to the study.
- 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.
In case the switch has been due to side-effects or by a personal preference of
the patient (such as the wish to switch to oral therapies), this is not
considered as an exclusion criterium.
3. 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
4. Patients that have previously used interferon-beta and have been tested
positive for neutralizing antibodies (NAbs).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is number of patients with return of inflammatory disease<br /><br>activity after 2 years based on: a clinically confirmed relapse (defined<br /><br>according to the definition most often used in MS phase-III trials: the onset<br /><br>of new or recurrent symptoms that last > 24 hours, that are accompanied by new<br /><br>objective abnormalities on a neurological examination and that are not<br /><br>explained by non-MS processes such as fever, infection, severe stress or drug<br /><br>toxicity (Gold et al NEJM 2012)) , or any emerging subclinical disease activity<br /><br>proven to be due to active disease/new inflammation (defined as 3 or more<br /><br>lesions on T2*weighted images or 2 or more gadolinium enhancing lesions on<br /><br>T1-weighted post-contrast MRI suggestive of demyelination) in the<br /><br>discontinuation group.</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Changes in neurological functioning: EDSS-change, MSFC-change (timed 25-foot<br /><br>walk test, 9-hole peg test, symbol digits modality test)<br /><br>- Individual MRI-parameters: T1 post-contrast lesion numbers, T2 lesion<br /><br>numbers, atrophy measurements.<br /><br>- Changes in quality of life measurements: MSIS-29, short form health survey<br /><br>(SF-36), CIS20r, MSSE, Treatment Satisfaction Questionnaire for Medication<br /><br>(TSQM), EQ5D-5L, iMCQ, iPCQ.<br /><br>- Changes in biomarker measurements (neurofilament light).<br /><br>- OCT and eye movement measurements: peri-papillary retinal nerve fiber (RNFL)<br /><br>thickness, macular ganglion cell-layer inner plexiform layer (GCL-IPL)<br /><br>thickness, eye movement measurements<br /><br>- Changes in digital biomarkers using the NeuroKeys and MS sherpa mobile<br /><br>applications: 2-minute walking test, cognition test, questionnaire, keystroke<br /><br>data.</p><br>