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Possible Role of Butyrylcholinesterase in Fat Loss and Decreases in Inflammatory Levels in Patients with Multiple Sclerosis after Treatment with Epigallocatechin Gallate and Coconut Oil: A Pilot Study.
de la Rubia Ortí, JE, Platero, JL, Yang, IH, Ceron, JJ, Tvarijonaviciute, A, Sabater, PS, Benlloch, M, Sancho-Cantus, D, Sancho, S
Nutrients. 2021;(9)
Abstract
(1) Background. Multiple sclerosis (MS) is characterised by the loss of muscle throughout the course of the disease, which in many cases is accompanied by obesity and related to inflammation. Nonetheless, consuming epigallocatechin gallate (EGCG) and ketone bodies (especially β-hydroxybutyrate (βHB)) produced after metabolising coconut oil, have exhibited anti-inflammatory effects and a decrease in body fat. In addition, butyrylcholinesterase (BuChE), seems to be related to the pathogenesis of the disease associated with inflammation, and serum concentrations have been related to lipid metabolism. Objective. The aim of the study was to determine the role of BuChE in the changes caused after treatment with EGCG and ketone bodies on the levels of body fat and inflammation state in MS patients. (2) Methods. A pilot study was conducted for 4 months with 51 MS patients who were randomly divided into an intervention group and a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, and the control group was prescribed a placebo. Fat percentage and concentrations of the butyrylcholinesterase enzyme (BuChE), paraoxonase 1 (PON1) activity, triglycerides, interleukin 6 (IL-6), albumin and βHB in serum were measured. (3) Results. The intervention group exhibited significant decreases in IL-6 and fat percentage and significant increases in BuChE, βHB, PON1, albumin and functional capacity (determined by the Expanded Disability Status Scale (EDSS)). On the other hand, the control group only exhibited a decrease in IL-6. After the intervention, BuChE was positively correlated with the activity of PON1, fat percentage and triglycerides in the intervention group, whereas these correlations were not observed in the control group (4). Conclusions. BuChE seems to have an important role in lipolytic activity and the inflammation state in MS patients, evidenced after administering EGCG and coconut oil as a βHB source.
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Lifestyle, Exercise and Activity Package for People living with Progressive Multiple Sclerosis (LEAP-MS): adaptions during the COVID-19 pandemic and remote delivery for improved efficiency.
Lowe, R, Barlow, C, Lloyd, B, Latchem-Hastings, J, Poile, V, Scoble, C, Dean-Young, A, Button, K, Playle, R, Busse, M
Trials. 2021;(1):286
Abstract
The LEAP-MS (Lifestyle, Exercise and Activity Package for People living with Progressive Multiple Sclerosis) study has developed an individualised supported self-management approach for physical activity for people with progressive multiple sclerosis (MS) and severe disability. The intervention has been evaluated in a single-arm feasibility study with embedded process evaluation. The feasibility study was due to open to recruitment during the COVID-19 2020-2021 pandemic, 1 month into the first UK-wide lockdown. We worked rapidly to implement adaptions to the trial procedures and intervention delivery that we believe are applicable to randomised controlled trials. Recruitment became predominantly via self-referral. Electronic consent was employed, with consent discussions occurring over the telephone. Registration, consent, eligibility assessment and data collection as well as the intervention (online physical activity tool) were via a secure, encrypted multi-user web-based platform for participants, physiotherapists and researchers accessible via various hardware. Physiotherapy consultations, as well as the process evaluation, were conducted remotely using video conferencing software or the telephone. A remote training package for physiotherapists and site initiations was also developed and electronic site files employed. Our adaptions are extremely topical given the COVID-19 situation, and whilst not what we had originally planned, have enabled successful delivery of the feasibility study and are relevant to conducting randomised controlled trials and meeting the needs of people with MS who are far more isolated than ever before. TRIAL REGISTRATION ClinicalTrials.gov NCT03951181 . Registered on 15 May 2019.
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Dalfampridine to Improve Balance in Multiple Sclerosis: Substudy from a Randomized Placebo-Controlled Trial.
Prosperini, L, Castelli, L, De Giglio, L, Bonanno, V, Gasperini, C, Pozzilli, C
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2020;(2):704-709
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Abstract
This was a substudy of a randomized, double-blind, placebo-controlled trial originally designed to explore the effect of dalfampridine on information processing speed (2013-002558-64 EU Clinical Trials Register) in patients with multiple sclerosis (MS). A total of 120 patients were originally randomized in a 2:1 ratio to receive dalfampridine 10 mg or placebo twice daily for 12 weeks. Here, we sought to explore the effect of dalfampridine on static balance in single-task and dual-task conditions in a subgroup of 41 patients. They underwent static posturography in quiet standing (single-task) and while performing the Stroop test (dual-task) at randomization (baseline), after 12 weeks and after a 4-week wash-out period. Baseline characteristics of active group (n = 27) did not differ from those of placebo group (n = 14). Dalfampridine treatment was associated with better balance control than placebo in both single-task (F = 4.80, p = 0.034) and dual-task (F = 6.42, p = 0.015) conditions, with small-to-moderate effect sizes (Cohen's f2 = 0.122-0.162). The beneficial effect of dalfampridine was not retained 4 weeks after its discontinuation. The rate of accidental falls per month did not differ between the two groups (p = 0.12). Our preliminary findings suggest that dalfampridine can be considered a potential option to treat balance impairment due to MS. Larger sample sizes are needed to verify if the beneficial effect of dalfampridine on balance can be translated into a reduced risk of accidental falls.
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Safety and feasibility of various fasting-mimicking diets among people with multiple sclerosis.
Roman, SN, Fitzgerald, KC, Beier, M, Mowry, EM
Multiple sclerosis and related disorders. 2020;:102149
Abstract
BACKGROUND Fasting-mimicking diets have shown promise in experimental autoimmune encephalitis and are currently being investigated among people with multiple sclerosis (MS). Ensuring adherence to diet changes is critical to determining the efficacy of such interventions. OBJECTIVE Our primary aim was to evaluate the safety and feasibility of several fasting-mimicking diets and investigate whether various levels of clinical support improve diet adherence among people with MS. Secondarily, this study evaluated the impact of fasting-mimicking diets on weight and patient-reported outcomes (PROs). METHODS We conducted three pilot studies (two randomized controlled for 6 months; one randomized with transition to single arm) restricting either the amount or timing of calorie intake over 24 or 48 weeks. Interventions included calorie restriction (daily or intermittently) or time-restricted feeding. Adherence measures varied across studies but were collected at study visits along with weight and PRO data. RESULTS A total of 90 participants enrolled; 70 completed the studies, with no serious adverse events reported. Overall adherence to the calorie restriction diets was poor. When participants were tasked with maintaining a diet in a pragmatic setting, neither previously completed intense clinical support and education, nor weekly electronic communication throughout the diet period appeared to improve diet adherence. Participants who were able to adhere to a calorie restriction diet predictably lost weight. In contrast to calorie restriction, adherence to a time-restricted feeding (TRF) diet was relatively good. No statistically significant changes in PROs were observed in an intention-to-treat analysis. CONCLUSION The role diet may play in clinical outcomes in MS remains unknown, as class I evidence is lacking. Diet adherence remains a primary barrier to the feasible conduct of large, randomized controlled diet trials. Strict adherence to a TRF dietary change may be more feasible than calorie restriction and should be considered in future fasting-mimicking diet trials. ClinicalTrials.gov Registry:A Pilot Study of Intermittent Calorie Restriction in Multiple Sclerosis - NCT02647502. A Pragmatic Trial of Dietary Programs in People with Multiple Sclerosis (MS) - NCT02846558.
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Calling Out MS Fatigue: Feasibility and Preliminary Effects of a Pilot Randomized Telephone-Delivered Exercise Intervention for Multiple Sclerosis Fatigue.
Kratz, AL, Atalla, M, Whibley, D, Myles, A, Thurston, T, Fritz, NE
Journal of neurologic physical therapy : JNPT. 2020;(1):23-31
Abstract
BACKGROUND AND PURPOSE Fatigue is a common and debilitating symptom of multiple sclerosis (MS). Exercise therapy is effective in reducing MS-related fatigue; however, its feasibility, acceptability, and effectiveness when delivered over the telephone remain unknown. This randomized study aimed to determine the feasibility and acceptability of a telephone-delivered exercise intervention for MS-related fatigue. In addition, pre-/postchange in fatigue and secondary outcomes were compared with an otherwise identical in-person delivered exercise intervention. METHODS Twenty participants with MS and clinically significant fatigue were randomized to 8 sessions of either telephone (n = 10) or in-person (n = 10) delivered exercise therapy. Primary outcome measures concerned feasibility (number of sessions attended), acceptability (Client Satisfaction Questionnaire), and fatigue (Fatigue Severity Scale and two 11-point numeric rating scales: fatigue intensity and interference). Data on a range of secondary outcome measures were also collected. RESULTS There was no difference in average session attendance by group (telephone group: 7.6 ± 1.3 sessions; in-person 7.8 ± 0.42). Acceptability and reductions in fatigue were observed regardless of group, and improvements in a range of secondary outcomes were comparable. DISCUSSION AND CONCLUSIONS A telephone-delivered exercise intervention that targets MS-related fatigue is both feasible and acceptable. Primary and secondary outcome measures signaled that telephone-delivered exercise may be an effective mode of delivery that overcomes barriers to care in persons with MS and warrants testing in larger efficacy trials.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A293).
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Achillea millefolium is beneficial as an add-on therapy in patients with multiple sclerosis: A randomized placebo-controlled clinical trial.
Ayoobi, F, Moghadam-Ahmadi, A, Amiri, H, Vakilian, A, Heidari, M, Farahmand, H, Fathollahi, MS, Fatemi, I, Shafiei, SA, Alahtavakoli, M, et al
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2019;:89-97
Abstract
BACKGROUND Multiple sclerosis (MS) is a neurological disease for which to date there is no cure and the existing disease-modifying drugs just slow down the disease progression. PURPOSE In this clinical trial we evaluated the efficacy of Achillea millefolium (A. millefolium) aqueous extract in MS patients. METHODS A triple-blind randomized placebo-controlled parallel group trial was conducted on 75 MS patients. The patients were randomized into three groups including placebo and two groups receiving A. millefolium with two different doses, i.e. 250 mg/day and 500 mg/day, for 1 year. The primary outcome was the annualized relapse rate. Also, number and volume of lesions were obtained from magnetic resonance imaging (MRI) scans. Furthermore, we performed a comprehensive neurological and cognitive tests as follows: changes in the expanded disability status scale (EDSS), the multiple sclerosis functional composite (MSFC), fatigue severity scale (FSS), Ashworth spasticity assessment, Beck depression test, State-trait anxiety inventory (STAI), mini-mental status examination (MMSE), Wisconsin card sorting test (WCST), tower of London test (TOL), word-pair learning, paced auditory serial addition task (PASAT) and standard laboratory tests. RESULTS This study showed one year administration of A. millefolium (both doses) decreased the annual relapse rate in MS patients. The mean volume change of lesions significantly decreased in the 500 mg A. millefolium group. The add-on therapy also increased time to first relapse and the MSFC z-score; it decreased the EDSS score and improved performance in word-pair learning, PASAT, and WCST. CONCLUSION We found beneficial effects of A. millefolium aqueous extract as an add-on therapy in MS patients.
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Predicting responsiveness to fampridine in gait-impaired patients with multiple sclerosis.
Filli, L, Werner, J, Beyer, G, Reuter, K, Petersen, JA, Weller, M, Zörner, B, Linnebank, M
European journal of neurology. 2019;(2):281-289
Abstract
BACKGROUND AND PURPOSE Fampridine leads to significant improvements in walking in many people with multiple sclerosis (PwMS). However, a relevant proportion of PwMS does not respond to fampridine and predictors of initial drug responsiveness are unknown. METHODS Drug response to prolonged-release (PR)-fampridine was assessed in 55 PwMS using the timed 25-foot walk (T25FW), 6-min walk test (6MWT) and 12-item multiple sclerosis walking scale as outcome parameters. Patients were treated with PR-fampridine and placebo for 6 weeks each in a randomized, double-blind, placebo-controlled trial with crossover design (NCT01576354). Possible predictors of drug responsiveness were investigated by multiple correlation analysis and binary logistic regression models. An additional longitudinal analysis followed the drug responses of 32 patients treated with PR-fampridine over 3 years to identify potential predictors of long-term drug responsiveness. RESULTS Severity of walking disability was positively correlated with enhanced responses to PR-fampridine. The strongest single predictor of drug responsiveness was poor 6MWT performance at baseline, which was positively correlated with enhanced drug response in the 6MWT (R = -0.541; P < 0.001). A multivariable logistic regression model including 6MWT and T25FW baseline performances predicted PR-fampridine responder status with an accuracy of 85.5% (specificity, 90.0%; sensitivity, 73.3%), with a threshold of 211 m in the 6MWT best separating responders from non-responders. Enhanced drug responsiveness after 3 years correlated with decline in walking endurance during this period (R = -0.634; P = 0.001). CONCLUSIONS Initial walking impairment is a good predictor of therapeutic responsiveness to PR-fampridine. Valid predictors of patients' responsiveness to PR-fampridine are essential for patient stratification and optimization of multiple slcerosis treatment.
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The effect of retinyl-palmitate on the level of pro and anti-inflammatory cytokines in multiple sclerosis patients: A randomized double blind clinical trial.
Bitarafan, S, Mohammadpour, Z, Jafarirad, S, Harirchian, MH, Yekaninejad, MS, Saboor-Yaraghi, AA
Clinical neurology and neurosurgery. 2019;:101-105
Abstract
OBJECTIVE Multiple sclerosis (MS) is an inflammatory and autoimmune disease associated with the imbalance of cytokines secreted from CD4+ T cells. Studies have shown that vitamin A and its active derivatives are able to modulate the immune system in MS patients. The aim of the present study was to investigate the effect of supplementation of retinyl palmitate (RP), the dietary form of vitamin A, on pro- and anti-inflammatory cytokines in the plasma and supernatants of cultured peripheral blood mononuclear cells (PBMCs) of MS patients. PATIENTS AND METHODS Thirty-six relapsing-remitting MS patients were enrolled in this double-blind randomized clinical trial. Participants received one capsule of 25,000 IU RP or a placebo per day for six months. Blood samples were taken before and after intervention. After intervention, the PBMCs were isolated and cultured. The levels of pro- and anti-inflammatory cytokines in the plasma and supernatant of cells stimulated with myelin oligodendrocyte glycoprotein, phytohemagglutinin or vehicle (media) were determined. The sample t-test and Mann Whitney U test were used to compare data between groups. RESULTS The changes in pro-inflammatory cytokine levels (IL-1β, TNF-α, IFN- γ, IL-2, IL-6, and IL-17) in the serum and supernatant of MS patients were not significant (p > 0.05). There were also no significant changes in the levels of anti-inflammatory cytokines (IL-10, IL-13, IL-4, and TGF-β) (p > 0.05). CONCLUSION Unexpectedly, this study found no significant changes in cytokine levels after six months of RP supplementation in MS patients. The results of other studies by our team have shown significant changes in the gene expression of the cytokines in response to RP supplements. Therefore, we recommend that periodic follow-up of RP supplementation may be needed to reveal changes in the level of the cytokines in the plasma and PBMCs and to clarify the real effect of RP on the immune factor levels in the serum of MS patients.
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MD1003 (High-Dose Pharmaceutical-Grade Biotin) for the Treatment of Chronic Visual Loss Related to Optic Neuritis in Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study.
Tourbah, A, Gout, O, Vighetto, A, Deburghgraeve, V, Pelletier, J, Papeix, C, Lebrun-Frenay, C, Labauge, P, Brassat, D, Toosy, A, et al
CNS drugs. 2018;(7):661-672
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Abstract
BACKGROUND Chronic visual loss is a disabling feature in patients with multiple sclerosis (MS). It was recently shown that MD1003 (high-dose pharmaceutical-grade biotin or hdPB) may improve disability in patients with progressive MS. OBJECTIVE The aim of this study was to evaluate whether MD1003 improves vision compared with placebo in MS patients with chronic visual loss. METHODS The MS-ON was a 6-month, randomized, double-blind, placebo-controlled study with a 6-month open-label extension phase. Adult patients with MS-related chronic visual loss of at least one eye [visual acuity (VA) below 0.5 decimal chart] were randomized 2:1 to oral MD1003 300 mg/day or placebo. The selected eye had to show worsening of VA within the past 3 years following either acute optic neuritis (AON) or slowly progressive optic neuropathy (PON). The primary endpoint was the mean change from baseline to month 6 in VA measured in logarithm of the minimum angle of resolution (logMAR) at 100% contrast of the selected eye. Visually evoked potentials, visual field, retinal nerve fiber layer (RNFL) thickness, and health outcomes were also assessed. RESULTS Ninety-three patients received MD1003 (n = 65) or placebo (n = 28). The study did not meet its primary endpoint, as the mean change in the primary endpoint was nonsignificantly larger (p = 0.66) with MD1003 (- 0.061 logMAR, + 3.1 letters) than with placebo (- 0.036 logMAR, + 1.8 letters). Pre-planned subgroup analyses showed that 100% contrast VA improved by a mean of + 2.8 letters (- 0.058 logMAR) with MD1003 and worsened by - 1.5 letters (+ 0.029 logMAR) with placebo (p = 0.45) in the subgroup of patients with PON. MD1003-treated patients also had nonsignificant improvement in logMAR at 5% contrast and in RNFL thickness and health outcome scores when compared with placebo-treated patients. There was no superiority of MD1003 vs placebo in patients with AON. The safety profile of MD1003 was similar to that of placebo. CONCLUSIONS MD1003 did not significantly improve VA compared with placebo in patients with MS experiencing chronic visual loss. An interesting trend favoring MD1003 was observed in the subgroup of patients with PON. Treatment was overall well tolerated. TRIAL REGISTRATION EudraCT identifier 2013-002112-27. ClinicalTrials.gov Identifier: NCT02220244 FUNDING MedDay Pharmaceuticals.
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Flavonoid rich dark cocoa may improve fatigue in people with multiple sclerosis, yet has no effect on glycaemic response: An exploratory trial.
Coe, S, Axelsson, E, Murphy, V, Santos, M, Collett, J, Clegg, M, Izadi, H, Harrison, JM, Buckingham, E, Dawes, H
Clinical nutrition ESPEN. 2017;:20-25
Abstract
CONTEXT Current research suggests that dark cocoa may reduce fatigue; however, the effect on fatigue in people with MS (pwMS) has never been established. The objective of this feasibility study was to explore the acute effect of high flavonoid cocoa on measures of fatigue and glycaemic response. METHODS This was a randomised crossover participant blind exploratory study in 12 participants (2 male and 10 female) with MS-related fatigue (>4 on the Fatigue Severity Scale; FSS). After fasting overnight, participants consumed the high flavonoid cocoa drink (350 mg gallic acid equivalents {GAE}/g) or a low flavonoid cocoa control (120 mg GAE/g), consuming the alternative drink on the next visit. Fatigue was self-reported on a 100 mm visual analogue scale at 30-min time intervals for 2 h post cocoa consumption and every 2 h for the rest of the day. Fatigability was monitored using a 6 min walk test (6MWT) at the end of the visit (2 h), and activity monitors worn for 24 h commencing at 12 noon on the day of testing. The feasibility of performing the trial including outcome measures was documented. RESULTS A moderate effect was found in self-reported fatigue throughout the day in favour of the high flavonoid group (Cohen's d 0.32, 95% non-central t CI -0.57 to 1.20). Fatigability measures did not change. Participants consumed and enjoyed the cocoa, all participants completed the study and outcome measures were accepted. CONCLUSION The results of this study support further trials to investigate the feasibility and efficacy of pure cocoa as a dietary supplement for fatigue in pwMS.