A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Quantitative assessment of sustained-release 4-aminopyridine for symptomatic treatment of multiple sclerosis. A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS). Vitamin D supplementation improves neuromuscular function in older people who fall. Evaluation of the effectiveness of professionally guided self-care for people with multiple sclerosis living in the community: a randomized controlled trial. Combining beta interferon and atorvastatin may increase disease activity in multiple sclerosis. High dose vitamin E therapy in amyotrophic lateral sclerosis as add-on therapy to riluzole: results of a placebo-controlled double-blind study. Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients. A randomised controlled trial comparing rehabilitation against standard therapy in multiple sclerosis patients receiving intravenous steroid treatment.
Low vitamin D status has been associated with multiple sclerosis (MS) prevalence and risk, but the therapeutic potential of vitamin D in established MS has not been explored. Our aim was to assess the tolerability of high-dose oral vitamin D and its impact on biochemical, immunologic, and clinical outcomes in patients with MS prospectively.
                An open-label randomized prospective controlled 52-week trial matched patients with MS for demographic and disease characteristics, with randomization to treatment or control groups. Treatment patients received escalating vitamin D doses up to 40,000 IU/day over 28 weeks to raise serum 25-hydroxyvitamin D [25(OH)D] rapidly and assess tolerability, followed by 10,000 IU/day (12 weeks), and further downtitrated to 0 IU/day. Calcium (1,200 mg/day) was given throughout the trial. Primary endpoints were mean change in serum calcium at each vitamin D dose and a comparison of serum calcium between groups. Secondary endpoints included 25(OH)D and other biochemical measures, immunologic biomarkers, relapse events, and Expanded Disability Status Scale (EDSS) score.
                Forty-nine patients (25 treatment, 24 control) were enrolled [mean age 40.5 years, EDSS 1.34, and 25(OH)D 78 nmol/L]. All calcium-related measures within and between groups were normal. Despite a mean peak 25(OH)D of 413 nmol/L, no significant adverse events occurred. Although there may have been confounding variables in clinical outcomes, treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls.
                High-dose vitamin D (approximately 10,000 IU/day) in multiple sclerosis is safe, with evidence of immunomodulatory effects.
                This trial provides Class II evidence that high-dose vitamin D use for 52 weeks in patients with multiple sclerosis does not significantly increase serum calcium levels when compared to patients not on high-dose supplementation. The trial, however, lacked statistical precision and the design requirements to adequately assess changes in clinical disease measures (relapses and Expanded Disability Status Scale scores), providing only Class level IV evidence for these outcomes. To evaluate the efficacy of 4-aminopyridine sustained release (4AP SR) (fampridine, EL-970) using quantitative measures of motor function in multiple sclerosis (MS) patients.
                In vitro, 4AP improves conduction through demyelinated axons. A previous multicenter trial of 4AP SR using the Expanded Disability Status Scale (EDSS) as the primary outcome was unable to establish clinical efficacy.
                Ten MS patients with stable motor deficits (EDSS 6.0-7.5) were given 4AP SR 17.5 mg bid and placebo for 1 week each in a double-blind, placebo-controlled, crossover trial. Time to walk 8 meters, time to climb four stairs, maximum voluntary isometric contraction measured quantitatively (MVICT), manual muscle testing (MMT), grip strength, EDSS, and the patient's global impression were measured.
                Timed gait was improved on 4AP SR compared with placebo in 9 of 10 subjects (p = 0.02). Timed stair climbing, MVICT, MMT, grip strength, and EDSS showed nonsignificant improvements on 4AP SR. Based on their global impressions, seven subjects preferred 4AP SR over placebo; only one preferred placebo. There were no serious side effects.
                4AP SR improved motor function in MS patients. The quantitative outcomes used in this study permit more sensitive evaluation of the therapeutic effect and promise to be useful in future trials of symptomatic treatments for MS. To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge.
                Multicenter, randomized, controlled trial with a factorial design.
                Five hospitals in Auckland, New Zealand, and Sydney, Australia.
                Two hundred forty-three frail older people.
                Patients were randomized to receive a single dose of vitamin D (calciferol, 300,000 IU) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits.
                The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months. Physical performance and self-rated function were secondary endpoints. Assessments took place in the participants' homes at 3 and 6 months after randomization and were performed by blinded assessors.
                There was no effect of either intervention on physical health or falls, but patients in the exercise group were at increased risk of musculoskeletal injury (risk ratio = 3.6, 95% confidence interval = 1.5-8.0). Vitamin D supplementation did not improve physical performance, even in those who were vitamin D deficient (<12 ng/mL) at baseline.
                Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization. There was no effect of vitamin D on physical performance, and the exercises increased the risk of musculoskeletal injury. These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people. vitamin D supplementation reduces the incidence of fractures in older adults. This may be partly mediated by effects of vitamin D on neuromuscular function.
                to determine the effects of vitamin D supplementation on aspects of neuromuscular function known to be risk factors for falls and fractures.
                randomised, double-blind, placebo-controlled study.
                falls clinic taking referrals from general practitioners and accident and emergency department.
                139 ambulatory subjects (>/=65 years) with a history of falls and 25-hydroxyvitamin D (25OHD) </=12 microg/l. Intervention: patients were randomised to receive a single intramuscular injection of 600,000 i.u. ergocalciferol or placebo.
                assessments including biochemistry, postural sway, choice reaction time (CRT), aggregate functional performance time (AFPT), and quadriceps strength were carried out at baseline and 6 months post-intervention.
                baseline characteristics were comparable between both groups. 25OHD in the treatment group increased significantly at 6 months. AFPT deteriorated in the control group and improved in the intervention group, representing a significant difference between groups (+6.6 s versus -2.0 s, t = 2.80, P < 0.05). Similar changes were observed for CRT (-0.06 s versus +0.41 s, t = -2.52, P < 0.01) and postural sway (+0.0025 versus -0.0138, t = 2.35, P < 0.02). There was no significant difference in muscle strength change between groups (-10 N versus -2 N, t = -1.26, ns). A significant correlation between change in AFPT and change in 25OHD levels was observed (r = 0.19, P = 0.03). There was no significant difference in the number of falls (0.39 versus 0.24, t = 1.08, P = 0.28) or fallers (14 versus 11, P = 0.52) between two groups.
                vitamin D supplementation, in fallers with vitamin D insufficiency, has a significant beneficial effect on functional performance, reaction time and balance, but not muscle strength. This suggests that vitamin D supplementation improves neuromuscular or neuroprotective function, which may in part explain the mechanism whereby vitamin D reduces falls and fractures. The aim of the study was to assess the efficacy of a patient-focused professionally guided self-care programme for the management of multiple sclerosis (MS) in the community.
                This was a single-blind randomized controlled trial.
                The study was conducted with people with MS living in the community.
                Two hundred and seventy-eight people with MS were invited to take part in the study. One hundred and eighty-nine people consented to take part (68%). Of these 183 began the study and 169 (92.3%) completed it. Seventy-three individuals were in the intervention group and 96 were in the control group.
                The intervention comprised discussion of self-care based on client priorities, using an information booklet about self-care.
                These included the Barthel Index, a measure of mobility, the SF-36, and the Standard Day Dependency Record (SDDR) which measures the need for assistance with daily activities. Assessments were conducted at baseline and again six months later.
                Changes in health status were small. However, at follow-up the intervention group had better SF-36 health scores, in mental health (p = 0.04), and vitality (p = 0.05) and considered help with daily activities to be less essential, as measured by the SDDR (p = 0.04), than the control group. Participants in the intervention group had maintained levels of independence at follow-up (p = 0.62) while the control group showed a significant decrease in independence (p= 0.001).
                This intervention could be a useful aid for health professionals who are supporting people with MS living in the community. To explore whether high-dose atorvastatin can be administered safely to persons with relapsing-remitting multiple sclerosis (MS) taking thrice weekly, 44 microg dose subcutaneous interferon beta-1a.
                Persons with clinically stable, relapsing-remitting MS, on standard high-dose subcutaneous interferon beta-1a, were randomized in a double-blind fashion to receive either placebo or atorvastatin at dosages of 40 or 80 mg/day for 6 months. Blinded neurologic examinations and brain MRI readings were obtained at months 0, 3, 6, and 9. Laboratory blood testing was performed monthly. Main outcome measures were the determination of drug toxicity using blood tests and ECG and determination of MS-related disease activity, either clinical relapses or new or contrast-enhancing lesions on MRI.
                Twenty-six subjects received at least one dose of study drug. Ten of 17 subjects on either 80 mg or 40 mg of atorvastatin per day had either new or enhancing T2 lesions on MRI or clinical relapses. One of the nine subjects on placebo had a relapse with active lesions on MRI. The subjects receiving atorvastatin were at greater risk for either clinical or MRI disease activity compared to placebo (p = 0.019). Significant changes in blood tests were noted only for lower cholesterol levels in subjects receiving atorvastatin.
                The combination of 40 or 80 mg atorvastatin with thrice weekly, 44 microg interferon beta-1a in persons with multiple sclerosis resulted in increased MRI and clinical disease activity. Caution is suggested in administering this combination. Increasing evidence has suggested that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E (alpha-tocopherol) has been shown to slow down the onset and progression of the paralysis in transgenic mice expressing a mutation in the superoxide dismutase gene found in certain forms of familial ALS. The current study, a double blind, placebo-controlled, randomised, stratified, parallel-group clinical trial, was designed to determine whether vitamin E (5000 mg per day) may be efficacious in slowing down disease progression when added to riluzole.
                160 patients in 6 German centres with either probable or definite ALS (according to the El Escorial Criteria) and a disease duration of less than 5 years, treated with riluzole, were included in this study and were randomly assigned to receive either alpha-tocopherol (5000 mg per day) or placebo for 18 months. The Primary outcome measure was survival, calculating time to death, tracheostomy or permanent assisted ventilation, according to the WFN-Criteria of clinical trials. Secondary outcome measures were the rate of deterioration of function assessed by the modified Norris limb and bulbar scales, manual muscle testing (BMRC), spasticity scale, ventilatory function and the Sickness Impact Profile (SIP ALS/19). Patients were assessed at entry and every 4 months thereafter during the study period until month 16 and at a final visit at month 18. Vitamin E samples were taken for compliance check and Quality Control of the trial. For Safety, a physical examination was performed at baseline and then every visit until the treatment discontinuation at month 18. Height and weight were recorded at baseline and weight alone at the follow-up visits. A neurological examination as well as vital signs (heart rate and blood pressure), an ECG and VEP's were recorded at each visit. Furthermore, spontaneously reported adverse experiences and serious adverse events were documented and standard laboratory tests including liver function tests performed. For Statistical Analysis, the population to be considered for the primary outcome measure was an "intent-to-treat" (ITT) population which included all randomised patients who had received at least one treatment dose (n = 160 patients). For the secondary outcome measures, a two way analysis of variance was performed on a patient population that included all randomised patients who had at least one assessment after inclusion.
                Concerning the primary endpoint, no significant difference between placebo and treatment group could be detected either with the stratified Logrank or the Wilcoxon test. The functional assessments showed a marginal trend in favour of vitamin E, without reaching significance.
                Neither the primary nor the secondary outcome measures could determine whether a megadose of vitamin E is efficacious in slowing disease progression in ALS as an add-on therapy to riluzol. Larger or longer studies might be needed. However, administration of this megadose does not seem to have any significant side effects in this patient population. To determine whether a low fat diet supplemented with omega-3 positively affects quality of life (QOL) in relapsing-remitting MS (RRMS) patients. In this 1-year long double-blind, randomized trial, patients were randomized to two dietary interventions: the "Fish Oil" (FO) group received a low fat diet (15% fat) with omega-3 FOs and the "Olive Oil" (OO) group received the AHA Step I diet (fat 30%) with OO supplements. The primary outcome measure was the Physical Components Summary Scale (PCS) of the Short Health Status Questionnaire (SF-36). Additional measures using MS specific QOL questionnaires, neurological status and relapse rate were obtained.
                31 RRMS patients were enrolled, with mean follow up over 11 +/- SD 2.9 months. Clinical benefits favoring the FO group were observed on PCS/SF-36 (P = 0.050) and MHI (P = 0.050) at 6 months. Reduced fatigue was seen on the OO diet at 6 months (P = 0.035). The relapse rate decreased in both groups relative to the rates during the 1 year preceding the study: mean change in relapse rate in the FO group: -0.79 +/- SD 1.12 relapses/year (P = 0.021) vs. -0.69 +/- SD 1.11 (P = 0.044) in the OO group. This study suggests that a low fat diet supplemented with omega-3 PUFA can have moderate benefits in RRMS patients on concurrent disease modifying therapies. There is evidence to support both the use of intravenous methylprednisolone (IVMP) in multiple sclerosis (MS) relapse and physiotherapy in the management of MS, but no studies have investigated the combination of steroids and rehabilitation together.
                To evaluate the benefits of IVMP with planned, comprehensive multidisciplinary team (MDT) care compared to IVMP with standard care.
                In this randomised controlled trial, patients confirmed to have had a definite MS relapse severe enough to warrant IVMP (1 g daily for three days) were randomised to two groups. The control group was managed according to the standard ward routine; the treatment group received planned coordinated multidisciplinary team assessment and treatment. Baseline assessments, including demographics and Expanded Disability Status Scale (EDSS) were carried out on both groups. The primary outcome measures were Guy's Neurological Disability Scale (GNDS), and Amended Motor Club Assessment (AMCA). The secondary measures were the Barthel Index (BI), Human Activity Profile (HAP), and Short Form Item 36 Health Survey (SF-36). All measures have published data on reliability and validity. Measures were administered at one and three months.
                Forty subjects, including 27 females, completed data collection. There were no significant differences between the two groups at baseline. Results showed statistically significant differences in GNDS (p = 0.03), AMCA (p = 0.03), HAPM (p < 0.01), HAPA (p = 0.02), and BI (p = 0.02) at three months in favour of planned MDT care.
                This study indicates that combining steroids with planned MDT care is superior to administering them in a standard neurology or day ward setting. Further research is necessary in order to confirm this finding.
The current level of evidence for the effectiveness of vitamin D supplementation in the management of people with MS is based on a single RCT with potential high risk of bias, which does not at present allow confident decision-making about the use of Vitamin D in MS. Therefore, until further high quality evidence is available, clinicians may wish to consider relevant MS guidelines on vitamin D supplementation when making decisions about the care of people with multiple sclerosis. Adequately powered, multi-centred RCTs with a focus on clinical as well as immunological and MRI outcomes that are meaningful to people with MS, and are able to provide insight into the benefits of Vitamin D in people with MS, are still required.