Dataset Information

Lipoic acid in secondary progressive MS: A randomized controlled pilot trial.

ABSTRACT: To determine whether lipoic acid (LA), an endogenously produced antioxidant, slowed the whole-brain atrophy rate and was safe in secondary progressive MS (SPMS).Patients with SPMS aged 40-70 years enrolled in a single center, 2-year, double-blind, randomized trial of daily oral 1,200 mg LA vs placebo. Primary outcome was change in annualized percent change brain volume (PCBV). Secondary outcomes were changes in rates of atrophy of segmented brain, spinal cord, and retinal substructures, disability, quality of life, and safety. Intention-to-treat analysis used linear mixed models.Participation occurred between May 2, 2011, and August 14, 2015. Study arms of LA (n = 27) and placebo (n = 24) were matched with mean age of 58.5 (SD 5.9) years, 61% women, mean disease duration of 29.6 (SD 9.5) years, and median Expanded Disability Status Score of 6.0 (interquartile range 1.75). After 2 years, the annualized PCBV was significantly less in the LA arm compared with placebo (-0.21 [standard error of the coefficient estimate (SEE) 0.14] vs -0.65 [SEE 0.10], 95% confidence interval [CI] 0.157-0.727, p = 0.002). Improved Timed 25-Foot Walk was almost but not significantly better in the LA than in the control group (-0.535 [SEE 0.358] vs 0.137 [SEE 0.247], 95% CI -1.37 to 0.03, p = 0.06). Significantly more gastrointestinal upset and fewer falls occurred in LA patients. Unexpected renal failure (n = 1) and glomerulonephritis (n = 1) occurred in the LA cohort. Compliance, measured by pill counts, was 87%.LA demonstrated a 68% reduction in annualized PCBV and suggested a clinical benefit in SPMS while maintaining favorable safety, tolerability, and compliance over 2 years.NCT01188811.This study provides Class I evidence that for patients with SPMS, LA reduces the rate of brain atrophy.

SUBMITTER: Spain R

PROVIDER: S-EPMC5489387 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Lipoic acid in secondary progressive MS: A randomized controlled pilot trial.

Spain Rebecca R Powers Katherine K Murchison Charles C Heriza Elizabeth E Winges Kimberly K Yadav Vijayshree V Cameron Michelle M Kim Ed E Horak Fay F Simon Jack J Bourdette Dennis D

Neurology(R) neuroimmunology & neuroinflammation 20170628 5

<h4>Objective</h4>To determine whether lipoic acid (LA), an endogenously produced antioxidant, slowed the whole-brain atrophy rate and was safe in secondary progressive MS (SPMS).<h4>Methods</h4>Patients with SPMS aged 40-70 years enrolled in a single center, 2-year, double-blind, randomized trial of daily oral 1,200 mg LA vs placebo. Primary outcome was change in annualized percent change brain volume (PCBV). Secondary outcomes were changes in rates of atrophy of segmented brain, spinal cord, a ...[more]

PMID: 28680916

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Project description:BackgroundPeople with chronic progressive multiple sclerosis (CPMS) have limited options in medical treatment. Enhancing physical activity (PA) might promote neuroregeneration in multiple sclerosis (MS) and positively influence disability, thus providing an alternative to medical treatment. Previous studies indicate that evidence-based patient information (EBPI) is essential for inducing behavioral change, e.g. enhancing PA.ObjectiveTo investigate feasibility of a smartphone app providing EBPI about the benefit of PA and a simple activity feedback to enhance PA in people with CPMS in a pilot randomized controlled trial over 3 months.MethodsThirty-eight people with CPMS (mean age 51 years, median Expanded Disability Status Scale 4.0) were 1:1 randomized into either a control group (n = 20) or an intervention group (n = 18). The intervention group received access to a multimedia EBPI app including activity feedback, texts, figures and videos. In the control group, participants received a leaflet with unspecific information about exercising in general. The EPBI itself was designed based on a systematic review. At baseline and after 3 months, all participants underwent clinical performance tests, filled in questionnaires and received an activity monitor (Actigraph®) for 7 days. The primary endpoint was the rate of responders defined as participants with a 20% increase of physical acitivity (time of moderate or vigiorous PA-MVPA) or 20% increase of the number of steps, both assessed with the activity monitor. As secondary endpoints, we compared accelerometry, performance and questionnaires adjusted for baseline measurments between the groups (ANCOVA). Moreover, we used questionnaires to compare knowledge about exercise (activity requiring physical effort, carried out to improve or improve health and fitness) in MS, usability of the app in general and motivation towards a more active lifestyle after 3 months in both groups.ResultsThe groups showed significant differences in disease duration and PA according to the Godin-Leisure Time Exercise Questionnaire at baseline. After 3 months, we detected no difference in the rate of responders, which was an overall 22%. However, MVPA significantly increased in both groups (p < 0.001) and the intervention group tended to have a higher motivation towards a more active lifestyle (Cohens D = 0.7, p = 0.09) as measured by the questionnaire. Reponses also showed, that participants appreciated the app but claimed a lack of interactivity as a short-coming.ConclusionJust providing information in a multimedia smartphone app did not enhance physical activitiy more than a simple leaflet in this small pilot trial in CPMS. However, the group of app users tended to have a higher motivation towards a more active lifestyle. Overall, the concept of a smartphone app to support an active lifestyle in MS is highly appreciated by participants.

Project description:Few randomized controlled trials (RCTs) report interventions targeting improvement of frailty status as an outcome.This RCT enrolled 117 older adults (65-79?years of age) in Toufen, Taiwan who scored 3-6 on The Chinese Canadian Study of Health and Aging Clinical Frailty Scale Telephone Version and then score ?1 on the Cardiovascular Health Study Phenotypic Classification of Frailty (CHS_PCF). With a two by two factorial design, subjects were randomly assigned to interventions (Exercise and nutrition, EN, n?=?55 or problem solving therapy, PST, n?=?57) or controls (non-EN, n?=?62 or non-PST, n?=?60). Educational booklets were provided to all. EN group subjects received nutrition consultation and a thrice-weekly exercise-training program while PST group subjects received 6 sessions in 3?month. Subjects were followed at 3, 6, and 12?months. Primary outcome was improvement of the CHS_PCF by at least one category (from pre-frail to robust, or from frail to pre-frail or robust) from baseline assessments. One hundred and one completed final assessments. Intention-to-treat analysis with the generalized estimating equation model was applied with adjustment for time and treatment-by-time interactions.Mean age was 71.4?±?3.7?years, with 59% females. Baseline characteristic were generally comparable between groups. EN group subjects had a higher improvement rate on the primary outcome than non-EN group subjects (45% vs 27%, adjusted p?=?0.008) at 3?months, but not 6 or 12?months. They also had more increase of serum 25(OH) vitamin D level (4.9?±?7.7 vs 1.2?±?5.4, p?=?0.006) and lower percentage of osteopenia (74% vs 89% p?=?0.042) at 12?months. PST group subjects had better improvement (2.7?±?6.1 vs 0.2?±?6.7, p?=?0.035, 6-month) and less deterioration (-3.5?±?9.7 vs -7.1?±?8.7, p?=?0.036, 12-month) of dominant leg extension power than non-PST subjects. Some secondary outcomes were also improved in control groups (non-EN or non-PST). No adverse effects were reported.The three-month EN intervention resulted in short-term (3-month) frailty status improvement and long-term effect on bone mineral density and serum vitamin D (12-month) among Taiwanese community-dwelling elders. The effect of PST was less pronounced.ClinicalTrials.gov: EC0970301

Project description:Background and objectivesImproved biomarkers of neuroprotective treatment are needed in progressive multiple sclerosis (PMS) to facilitate more efficient phase 2 trial design. The MS-STAT randomized controlled trial supported the neuroprotective potential of high-dose simvastatin in secondary progressive MS (SPMS). Here, we analyze serum from the MS-STAT trial to assess the extent to which neurofilament light (NfL) and neurofilament heavy (NfH), both promising biomarkers of neuroaxonal injury, may act as biomarkers of simvastatin treatment in SPMS.MethodsThe MS-STAT trial randomized patients to 80 mg simvastatin or placebo. Serum was analyzed for NfL and NfH using Simoa technology. We used linear mixed models to investigate the treatment effects of simvastatin compared with placebo on NfL and NfH. Additional models examined the relationships between neurofilaments and MRI and clinical measures of disease severity.ResultsA total of 140 patients with SPMS were included. There was no evidence for a simvastatin treatment effect on NfL or NfH: compared with placebo, NfL was 1.2% lower (95% CI 10.6% lower to 9.2% higher; p = 0.820) and NfH was 0.4% lower (95% CI 18.4% lower to 21.6% higher; p = 0.969) in the simvastatin treatment group. Secondary analyses suggested that higher NfL was associated with greater subsequent whole brain atrophy, higher T2 lesion volume, and more new/enlarging T2 lesions in the previous 12 months, as well as greater physical disability. There were no significant associations between NfH and MRI or clinical variables.DiscussionWe found no evidence of a simvastatin treatment effect on serum neurofilaments. While confirmation of the neuroprotective benefits of simvastatin is awaited from the ongoing phase 3 study (NCT03387670), our results suggest that treatments capable of slowing the rate of whole brain atrophy in SPMS, such as simvastatin, may act via mechanisms largely independent of neuroaxonal injury, as quantified by NfL. This has important implications for the design of future phase 2 clinical trials in PMS.Trial registration informationMS-STAT: NCT00647348.Classification of evidenceThis study provides class I evidence that simvastatin treatment does not have a large impact on either serum NfL or NfH, as quantified in this study, in SPMS.

Dataset Information

Lipoic acid in secondary progressive MS: A randomized controlled pilot trial.

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Lipoic acid in secondary progressive MS: A randomized controlled pilot trial.

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