PMC:3605436 / 4822-7485 JSONTXT

{"project":"NEUROSES","denotations":[{"id":"T155","span":{"begin":1706,"end":1716},"obj":"PM3425"},{"id":"T130","span":{"begin":487,"end":498},"obj":"CHEBI_51062"},{"id":"T131","span":{"begin":487,"end":498},"obj":"CHEBI_2679"},{"id":"T132","span":{"begin":988,"end":991},"obj":"PATO_0001978"},{"id":"T133","span":{"begin":1296,"end":1305},"obj":"PATO_0002532"},{"id":"T134","span":{"begin":1399,"end":1408},"obj":"PATO_0002532"},{"id":"T135","span":{"begin":1359,"end":1367},"obj":"PATO_0000173"},{"id":"T136","span":{"begin":1493,"end":1497},"obj":"PATO_0001026"},{"id":"T137","span":{"begin":1512,"end":1516},"obj":"PATO_0001026"},{"id":"T138","span":{"begin":1553,"end":1560},"obj":"PATO_0000001"},{"id":"T139","span":{"begin":1578,"end":1583},"obj":"PATO_0000574"},{"id":"T140","span":{"begin":1578,"end":1583},"obj":"PATO_0000569"},{"id":"T141","span":{"begin":1764,"end":1772},"obj":"PATO_0000228"},{"id":"T142","span":{"begin":1843,"end":1848},"obj":"PATO_0000008"},{"id":"T143","span":{"begin":1985,"end":1992},"obj":"CHEBI_38960"},{"id":"T144","span":{"begin":2054,"end":2058},"obj":"CHEBI_4614"},{"id":"T145","span":{"begin":2263,"end":2272},"obj":"CHEBI_31859"},{"id":"T146","span":{"begin":2277,"end":2287},"obj":"CHEBI_2618"},{"id":"T147","span":{"begin":2499,"end":2505},"obj":"PATO_0001056"},{"id":"T148","span":{"begin":2499,"end":2505},"obj":"PATO_0001555"},{"id":"T149","span":{"begin":2499,"end":2505},"obj":"PATO_0000070"},{"id":"T150","span":{"begin":519,"end":529},"obj":"PM3425"},{"id":"T151","span":{"begin":1661,"end":1671},"obj":"PM3425"},{"id":"T152","span":{"begin":1706,"end":1716},"obj":"PM3425"},{"id":"T153","span":{"begin":519,"end":529},"obj":"PM3425"},{"id":"T154","span":{"begin":1661,"end":1671},"obj":"PM3425"}],"text":"Trial conduct\nConsecutive patients prescribed natalizumab at the participating centers gave their written, informed consent to enter the study after the therapy decision was made. Patients were eligible for inclusion in the trial if they were prescribed natalizumab according to national guidelines, aged 18–65 years (both inclusive) at screening and presented with an FSMC sum score of ≥43 (at least mild fatigue at baseline, Table 1). Patients with no symptoms of fatigue, EDSS of ≥6, amphetamine medication or major depression, were not included.\n10.1371/journal.pone.0058643.t001 Table 1 Cut-off values for the Fatigue Scale for Motor and Cognitive functions (FSMC). The study was performed at 27 centers in Sweden (12), Norway (7), Austria (5) and Denmark (3). The patients attended 5 visits, (at baseline, month 3, 6, 9 and 12) over 12 months. The primary endpoint was fatigue associated with MS as measured by the FSMC total score change at 12 months, compared with baseline. Cut-off values for the clinical categories mild, moderate and severe MS-related fatigue are shown in Table 1. The FSMC allows for the evaluation of the physical component of fatigue, i.e. motor fatigue, as well as the cognitive component, separately, which were also evaluated at every visit and constituted secondary endpoints. To address other important aspects of the function and well-being of MS patients, secondary endpoints were assessed at baseline and at months 6 and 12. They were: Capacity for work (capacity for work questionnaire; CWQ), health related quality of life ((HRQoL) Short Form -12 questionnaire (SF-12)), sleepiness (Epworth Sleepiness Scale; ESS), depression (Center for Epidemiologic Studies Depression scale; CES-D), cognitive impairment (the Paced Auditory Serial Addition Test; PASAT, and Symbol Digit Modalities Test; SDMT), Speed of walking (6 Minute Walk Test; 6MWT), MS disease disability (Expanded Disability Status Scale; EDSS) and amount of walking e.g. a step counter was worn for seven days the week before the study visit.\nThe DMTs used prior to initialization of natalizumab were documented. All concomitant medications taken during the trial were recorded and special attention was paid to change in symptomatic fatigue therapy, e.g. modafinil and amantadine. Information on relapses, adverse events (AEs) and serious adverse events (SAEs) were collected.\nThe first patient's first visit was on March 23, 2009 and the last patient's last visit on June 30, 2011. EudraCT number for the Swedish protocol: 2008-008065-35. Clinical Trials.gov identifier: NCT00884481. The study was considered observational in Austria, Norway and Denmark."}