Does aerobic training alleviate fatigue and improve societal participation in patients with multiple sclerosis? A randomized controlled trial

Background: Evidence supporting the effectiveness of aerobic training, specific for fatigue, in severely fatigued patients with multiple sclerosis (MS) is lacking. Objective: To estimate the effectiveness of aerobic training on MS-related fatigue and societal participation in ambulant patients with severe MS-related fatigue. Methods: Patients ( N = 90) with severe MS-related fatigue were allocated to 16-week aerobic training or control intervention. Primary outcomes were perceived fatigue (Checklist Individual Strength (CIS20r) fatigue subscale) and societal participation. An improvement of ⩾8 points on the CIS20r fatigue subscale was considered clinically relevant. Outcomes were assessed by a blinded observer at baseline, 2, 4, 6 and 12 months. Results: Of the 89 patients that started treatment (median Expanded Disability Status Scale (interquartile range), 3.0 (2.0–3.6); mean CIS20r fatigue subscale (standard deviation (SD)), 42.6 (8.0)), 43 received aerobic training and 46 received the control intervention. A significant post-intervention between-group mean difference (MD) on the CIS20r fatigue subscale of 4.708 (95% confidence interval (CI) = 1.003–8.412; p = 0.014) points was found in favour of aerobic training that, however, was not sustained during follow-up. No effect was found on societal participation. Conclusion: Aerobic training in MS patients with severe fatigue does not lead to a clinically meaningful reduction in fatigue or societal participation when compared to a low-intensity control intervention.

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Cognitive behavioral therapy positively affects fatigue in patients with multiple sclerosis: Results of a randomized controlled trial

Multiple Sclerosis Journal ◽

10.1177/1352458517709361 ◽

2017 ◽

Vol 23 (11) ◽

pp. 1542-1553 ◽

Cited By ~ 18

Author(s):

Lizanne E van den Akker ◽

Heleen Beckerman ◽

Emma H Collette ◽

Jos WR Twisk ◽

Gijs Bleijenberg ◽

...

Keyword(s):

Multiple Sclerosis ◽

Randomized Controlled Trial ◽

Cognitive Behavioral Therapy ◽

Behavioral Therapy ◽

Controlled Trial ◽

Cognitive Behavioral ◽

Control Treatment ◽

Post Intervention ◽

Randomized Controlled ◽

Societal Participation

Background: Fatigue is a common symptom in multiple sclerosis (MS) and often restricts societal participation. Cognitive behavioral therapy (CBT) may alleviate MS-related fatigue, but evidence in literature is inconclusive. Objective: To evaluate the effectiveness of CBT to improve MS-related fatigue and participation. Methods: In a multi-center, assessor-masked, randomized controlled trial, participants with severe MS-related fatigue were assigned to CBT or control treatment. CBT consisted of 12 individual sessions with a psychologist trained in CBT, the control treatment consisted of three consultations with a MS nurse, both delivered over 16 weeks. Assessments were at baseline, 8, 16 (i.e. post-intervention), 26, and 52 weeks post-baseline. Primary outcomes were the Checklist Individual Strength-fatigue subscale (CIS20r fatigue) and the Impact on Participation and Autonomy questionnaire (IPA). Data were analyzed according to the intention-to-treat principle, using mixed-model analysis. Results: Between 2011 and 2014, 91 patients were randomized (CBT: n = 44; control: n = 47). Between-group analysis showed a positive post-intervention effect for CBT on CIS20r fatigue (T16: −6.7 (95% confidence interval (CI) = −10.7; −2.7) points) that diminished during follow-up (T52: 0.5 (95% CI = −3.6; 4.4)). No clinically relevant effects were found on societal participation. Conclusion: Severe MS-related fatigue can be reduced effectively with CBT in the short term. More research is needed on how to maintain this effect over the long term.

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Intravenous immunoglobulin (IVIG) treatment for patients with primary or secondary progressive multiple sclerosis - outline of a double-blind randomized, placebo-controlled trial

Multiple Sclerosis Journal ◽

10.1177/135245859700300217 ◽

1997 ◽

Vol 3 (2) ◽

pp. 149-152 ◽

Cited By ~ 11

Author(s):

D. Poehlau ◽

J. Federlein ◽

T. Postert ◽

M. Sailer ◽

F. Bethke ◽

...

Keyword(s):

Multiple Sclerosis ◽

Controlled Trial ◽

Progressive Multiple Sclerosis ◽

Phase Iii ◽

Ivig Treatment ◽

Double Blind ◽

Disability Status ◽

Chronic Progressive Multiple Sclerosis ◽

Phase Iii Study ◽

Two Measures

We present the design of a double-blind, randomised placebo-controlled phase III study to evaluate safety and efficacy of IVIG in the treatment of patients suffering from primary or secondary chronic progressive multiple sclerosis. The primary endpoint is disability. Two measures of disability were chosen in order to assess the primary end point: (a) sustained improvement (assessed at month 6, confirmed at month 9) and (b) progression to increasing disability of the disease (sustained for 3 months) at any time during the course of this 2 years study. The disability is measured by the Extended Disability Status Scale (EDSS). Secondary end points include the assessment of visual function, functions of the upper extremity, cognitive functions, depression and quality of life.

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Riboflavin Supplementation to Patients with Multiple Sclerosis does not Improve Disability Status nor is Riboflavin Supplementation Correlated to Homocysteine

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000170 ◽

2013 ◽

Vol 83 (5) ◽

pp. 281-290 ◽

Cited By ~ 9

Author(s):

Mahshid Naghashpour ◽

Nastaran Majdinasab ◽

Ghodratollah Shakerinejad ◽

Maryam Kouchak ◽

Mohammad H. Haghighizadeh ◽

...

Keyword(s):

Multiple Sclerosis ◽

Demyelinating Disease ◽

Reductase Activity ◽

Controlled Trial ◽

Riboflavin Deficiency ◽

Double Blind ◽

Serum Homocysteine ◽

Study Results ◽

Disability Status ◽

Before And After

Background: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Riboflavin is involved in myelin formation in nerve cells. Riboflavin is a precursor of flavin adenine D-nucleotide (FAD), which is a coenzyme of methylene tetrahydrofolate reductase (MTHFR), which is an important enzyme for remethylation of homocysteine. Riboflavin supplementation has been shown to affect the serum levels of homocysteine in healthy volunteers. The aim of the present study was to test the effect of riboflavin supplementation on the status and disability of patients with MS and whether this effect could be mediated by serum homocysteine levels. Materials and Methods: This was a randomized, double-blind, controlled trial in which 29 MS patients with a mean age of 33 were tested with riboflavin, and the placebo group, with a mean age of 31, received either riboflavin supplementation (10 mg) or the placebo daily for six months. Disability, measured by the Expanded Disability Status Scale (EDSS) scores, erythrocyte glutathione reductase activity coefficient (EGRAC), and serum homocysteine levels were measured before and after the study. Results: The mean ± SD of EDSS score was significantly decreased in both groups over the six months of the study (2.3 ± 0.7 vs. 1.6 ± 0.6 for the riboflavin group and 2.8 ± 1.1 vs. 2.3 ± 1.3 for the placebo groups. The comparison across both groups yielded a non-significant change (P = 0.001 and 0.02, respectively). No significant differences were observed between the two groups in terms of EGRAC, riboflavin deficiency levels by EGRAC category, and serum homocysteine levels before and after the study. Conclusion: Riboflavin supplementation (10 mg/day) to patients with MS does not improve disability status. It appears that this effect is not related to serum homocysteine levels.

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Free From Falls education and exercise program for reducing falls in people with multiple sclerosis: A randomized controlled trial

Multiple Sclerosis Journal ◽

10.1177/13524585211046898 ◽

2021 ◽

pp. 135245852110468

Author(s):

Michelle H Cameron ◽

Andrea Hildebrand ◽

Cinda L Hugos ◽

Grace I Judd ◽

Garnett McMillan ◽

...

Keyword(s):

Multiple Sclerosis ◽

Randomized Controlled Trial ◽

Controlled Trial ◽

Exercise Program ◽

Control Group ◽

Post Intervention ◽

Randomized Controlled ◽

Credible Intervals ◽

Falls In Older Adults ◽

The Impact

Background: People with multiple sclerosis (PwMS) fall frequently. Community-delivered exercise and education reduce falls in older adults, but their efficacy in multiple sclerosis (MS) is unknown. Objectives: To evaluate the impact of the Free From Falls (FFF) group education and exercise program on falls in PwMS. Methods: This was a prospective, assessor-blinded, two-arm parallel randomized controlled trial. Ninety-six participants were randomized to FFF (eight weekly 2 hour sessions) or the control condition (a fall prevention brochure and informing their neurologist of their fall history). Participants counted falls prospectively from enrollment through 6 months following intervention. Effects on fall frequency were evaluated by the Bayesian analysis. Results: The modeled mean fall frequency pre-intervention was 1.2 falls/month in the FFF group (95% credible intervals (CIs) = 0.8–2.0) and 1.4 falls/month in the control group (95% CI = 0.9–2.1). Fall frequency decreased by 0.6 falls/month in both groups over time (nadir 4–6 months post-intervention: FFF 0.6 falls/month (95% CI = 0.4–0.9); control 0.8 falls/month (95% CI = 0.5–1.1)). Conclusion: In-person group exercise and education are not superior to written education and neurologist-initiated interventions for preventing falls in PwMS.

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Obstructive sleep apnea is associated with fatigue in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458511432328 ◽

2011 ◽

Vol 18 (8) ◽

pp. 1159-1169 ◽

Cited By ~ 68

Author(s):

M Kaminska ◽

RJ Kimoff ◽

A Benedetti ◽

A Robinson ◽

A Bar-Or ◽

...

Keyword(s):

Multiple Sclerosis ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Apnea Hypopnea Index ◽

Severe Fatigue ◽

Obstructive Sleep ◽

Disability Status ◽

Fatigue Severity ◽

Relationship Of ◽

Multiple Sleep Latency

Background: Multiple sclerosis (MS) patients often suffer from fatigue. Objective: We evaluated the relationship of obstructive sleep apnea (OSA) to fatigue and sleepiness in MS patients. Methods: Ambulatory MS patients without known sleep disorders and healthy controls underwent diagnostic polysomnography and a multiple sleep latency test (objective sleepiness measure). Fatigue was measured with the Fatigue Severity Scale (FSS) and the Multidimensional Fatigue Inventory (MFI), and subjective sleepiness by Epworth Sleepiness Scale. Covariates included age, sex, body mass index, Expanded Disability Status Scale (EDSS), depression, pain, nocturia, restless legs syndrome, and medication. Results: OSA (apnea–hypopnea index ≥15) was found in 36 of 62 MS subjects and 15 of 32 controls. After adjusting for confounders, severe fatigue (FSS ≥5) and MFI-mental fatigue (>group median) were associated with OSA and respiratory-related arousals in MS, but not control subjects. Subjective and objective sleepiness were not related to OSA in either group. In a multivariate model, variables independently associated with severe fatigue in MS were severe OSA [OR 17.33, 95% CI 2.53–199.84], EDSS [OR 1.88, 95% CI 1.21–3.25], and immunomodulating treatment [OR 0.14, 95% CI 0.023–0.65]. Conclusions: OSA was frequent in MS and was associated with fatigue but not sleepiness, independent of MS-related disability and other covariates.

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Pilot trial of speed-intensive gait training on balance and walking in people with multiple sclerosis

International Journal of Therapy and Rehabilitation ◽

10.12968/ijtr.2020.0059 ◽

2020 ◽

Vol 27 (11) ◽

pp. 1-10

Author(s):

Herb I Karpatkin ◽

Allison Benson ◽

Nolan Gardner ◽

Naomi Leb ◽

Nicole Ramos ◽

...

Keyword(s):

Multiple Sclerosis ◽

Walking Speed ◽

Pilot Trial ◽

Gait Training ◽

Training Programme ◽

Expanded Disability Status Scale ◽

Post Intervention ◽

Safety And Efficacy ◽

Disability Status ◽

Walking Endurance

Background/Aims Diminished walking speed and endurance is commonly experienced by individuals with multiple sclerosis. Speed-intensive gait training has led to improvements in walking speed and endurance in other neurological populations; however, its effect in persons with multiple sclerosis is unknown. This pilot study examined the feasibility, safety and efficacy of speed-intensive gait training in a sample of people with multiple sclerosis. Methods A total of eight participants (five women, median Expanded Disability Status Scale 3.5) underwent a 6-week, twice weekly speed-intensive gait training programme. Walking speed and endurance, balance and fatigue were measured pre- and post-intervention. Results Speed-intensive gait training was feasible, with excellent adherence and safety. It proved effective, with improvements in walking speed (P=0.05), walking endurance (P=0.036) and balance (P=0.041) without an increase in fatigue. Conclusions The intermittent design of speed-intensive gait training may enable individuals with multiple sclerosis to achieve higher training volumes than traditional models. Although further study is warranted, rehabilitation clinicians should consider adding speed-intensive gait training as an intervention to improve walking and balance in this patient group.

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The Compensatory Increased BDNF and NGF in Patients with Multiple Sclerosis Following Home-based Aerobic Training and Vitamin D Supplementation During COVID-19 Outbreak

10.21203/rs.3.rs-629297/v1 ◽

2021 ◽

Author(s):

Elahe Bahmani ◽

Rastegar Hoseini ◽

Ehsan Amiri

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Aerobic Training ◽

Controlled Trial ◽

Vitamin D Supplementation ◽

Lifestyle Modifications ◽

Home Based ◽

Post Test ◽

Multiple Sclerosis Patients ◽

And Control

Abstract Background: Lifestyle modifications (physical activity and diet) are among the most promising strategies in MS rehabilitation. This study aimed to investigate the effect of home-based aerobic training and vitamin D supplementation in patients with multiple sclerosis during the COVID-19 outbreak.Methods: In this randomized, single-blinded, placebo-controlled trial, 38 females with Multiple sclerosis with EDSS: 3-5 (aged 20–40 years with body mass index [BMI] of 25–30 kg/m2) were randomly assigned into four groups: aerobic training + Vitamin D supplementation (AT+Vit D; n=10); aerobic training (AT; n=9); Vitamin D supplementation (Vit D; n=9), and Control (Placebo) (n=10). The AT program consisted of 50-70% of HRMax, 25-40 min/day, three days/wk for eight weeks. Participants in the Vit D group consumed 50000 IU of Vitamin D supplement capsules per week for eight weeks. The data were analyzed through paired t-test and one-way analysis of variance, as well as Tukey's post hoc test at the signification level of P<0.05.Results: BDNF and NGF levels improved significantly from pre-test to post-test within all experimental groups. BDNF and NGF decreased significantly in AT+Vit D, AT, and Vit D compared to C. Also, the results show that the AT+Vit D had significantly lower BDNF and NGF compared to AT (P=0.023 and P=0.011) and Vit D (P=0.001 and P=0.002). Conclusion: These findings suggest that the combination of AT+Vit D improves BDNF and NGF status more effectively than AT or Vit D alone in female Multiple sclerosis patients.

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Effects and mechanisms of differently cued and non-cued motor imagery in people with multiple sclerosis: A randomised controlled trial

Multiple Sclerosis Journal ◽

10.1177/1352458518795332 ◽

2018 ◽

Vol 25 (12) ◽

pp. 1593-1604 ◽

Cited By ~ 1

Author(s):

Barbara Seebacher ◽

Raija Kuisma ◽

Angela Glynn ◽

Thomas Berger

Keyword(s):

Multiple Sclerosis ◽

Motor Imagery ◽

Walking Speed ◽

Controlled Trial ◽

Walking Distance ◽

Post Intervention ◽

Sensorimotor Synchronisation ◽

Underlying Mechanisms ◽

Randomised Controlled ◽

Auditory Cueing

Background: Walking impairment and fatigue are prevalent symptoms in people with multiple sclerosis (PwMS). Motor imagery (MI) with rhythmic auditory cueing improved walking in PwMS, but so far, the underlying mechanisms are not fully explored. Objective: This study investigated the effects and mechanisms of differently cued and non-cued MI on walking, fatigue and quality of life (QoL) in PwMS. Methods: A total of 60 PwMS with mild to moderate disability were randomised to music- and verbally cued MI (MVMI), music-cued MI (MMI) or MI. Participants practised cued or non-cued MI of walking for 17 minutes, six times per week for 4 weeks at home. Primary outcomes were walking speed (timed 25-foot walk) and walking distance (6-minute walk test). Results: A total of 59 participants completed the study. All interventions induced significant improvements in walking speed and distance, while MVMI was superior. After cued MI, fatigue and QoL significantly improved, with greatest changes seen after MVMI. All participants showed high MI ability. Post-intervention, sensorimotor synchronisation (SMS) was significantly more accurate after cued MI. Conclusion: All interventions significantly improved walking. MVMI was superior in improving walking, fatigue and QoL. Results suggest that MI and SMS were mechanisms of action.

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A randomized trial to assess the efficacy of a psychoeducational intervention on caregiver burden in schizophrenia

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.003 ◽

2016 ◽

Vol 33 (1) ◽

pp. 9-17 ◽

Cited By ~ 12

Author(s):

M. Martín-Carrasco ◽

P. Fernández-Catalina ◽

A.I. Domínguez-Panchón ◽

M. Gonçalves-Pereira ◽

E. González-Fraile ◽

...

Keyword(s):

Caregiver Burden ◽

Standard Care ◽

Intervention Program ◽

Controlled Trial ◽

Intervention Group ◽

Psychoeducational Intervention ◽

Negative Consequences ◽

Post Intervention ◽

Control Intervention

AbstractBackgroundPatient's relatives usually care for patients with schizophrenia, and as informal caregivers they experience negative consequences. The aim of the EDUCA-III trial is to test the efficacy of a psychoeducational intervention program (PIP) versus standard care to reduce the caregiver burden at post-intervention (4 months), and at follow-up (8 months).MethodA two-arm, evaluator blind, multicentre, randomized controlled trial. The PIP group had 12 weekly group sessions. The control intervention group had the usual support and standard care. Primary outcomes were change scores since baseline on the Zarit Burden Interview (ZBI) and the Involvement Evaluation Questionnaire (IEQ).ResultsOne hundred and nine caregivers were randomized to PIP and 114 to control condition from 23 research sites. The decrease of ZBI scores was significantly higher on the PIP arm at 4 months (mean difference [MD] = −4.33; 95% CI −7.96, −0.71), and at 8 months (MD = −4.46; 95% CI −7.79, −1.13). There were no significant decreases in the IEQ scores (MD at 4 months = −2.80; 95% CI −6.27, 0.67; MD at 8 months = −2.85; 95% CI −6.51, 0.81).ConclusionsThe PIP condition seems to reduce caregiver burden.Trial registrationISRCTN32545295.

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Reliability of Outcome Measures in Clinical Trials in Secondary Progressive Multiple Sclerosis

Neurology ◽

10.1212/wnl.0000000000011123 ◽

2020 ◽

Vol 96 (1) ◽

pp. e111-e120 ◽

Cited By ~ 1

Author(s):

Marcus W. Koch ◽

Jop Mostert ◽

Pavle Repovic ◽

James D. Bowen ◽

Bernard Uitdehaag ◽

...

Keyword(s):

Multiple Sclerosis ◽

Outcome Measures ◽

Controlled Trial ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Disability Progression ◽

Secondary Progressive ◽

Randomized Controlled ◽

Disability Status ◽

Over Time

ObjectiveTo investigate the reliability of clinical outcomes in secondary progressive multiple sclerosis (SPMS) trials, we compared the frequency of progression and improvement events on different clinical outcome measures in the placebo arms of 2 large randomized controlled trial (RCT) datasets.MethodsUsing original trial data from the placebo arms of IMPACT (International MS Secondary Progressive Avonex Controlled Trial) and ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis), 2 large RCTs in SPMS, we compared disability progression and similarly defined improvement with and without 3- or 6-month confirmation on the outcome measures Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and their combinations.ResultsIn both datasets, the EDSS showed the highest rates of improvement over time, and the smallest difference between progression and improvement rates, followed by the T25FW and the 9HPT. For the T25FW and 9HPT, improvement rates were fairly stable over time and remained at below or around the 10% level. For the EDSS, improvement rates increased in parallel with disability progression rates.ConclusionsAll investigated outcome measures in SPMS showed some evidence of random variation and measurement error, the T25FW and 9HPT less so than the more established outcome EDSS. Our findings are relevant for the design and critical appraisal of trials in SPMS.

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