Assessing the efficacy of cell transplantation for Parkinson's Disease: a patient-centered approach

Background: Evidence from a growing number of preclinical studies indicate that recently discovered stem cell lines may be translated into viable cellular therapies for people with Parkinson’s disease. Objectives: In a brief but critical review, we examine the use of primary and secondary outcome measures currently used to evaluate the efficacy of cellular therapies. Methods: The current practice of relying on a single primary outcome measure does not appear to provide the evidence required for demonstrating the robust, life-changing recovery anticipated with the successful implementation of cellular therapies. Results: We propose a 360-degree assessment protocol, which includes co-primary and composite outcome measures to provide accurate and comprehensive evidence of treatment efficacy, from the perspectives of both the researchers and the patients

Integrating self-management support for knee injuries into routine clinical practice: TRAK intervention design and delivery

Background TRAK is a web-based intervention that provides knee patients with health information, personalised exercise plans and remote clinical support. The aim of this study was to fully define TRAK intervention content, setting and context and develop the training through an implementation study in a physiotherapy out-patient service. Methods A mixed methods study. Phase 1 was a qualitative interview study, whereby fifteen physiotherapists used TRAK for 1 month with a patient of their choice. Interviews explored patient and physiotherapist views of TRAK intervention and training requirements. In Phase 2 seventy-four patients were recruited, all received conventional physiotherapy, a subset of 48 patients used TRAK in addition to conventional Physiotherapy. Aspects of feasibility measured included: uptake and usage of TRAK. Results Patients and physiotherapists reported that TRAK was easy to use and highlighted the therapeutic benefit of the exercise videos and personalised exercise plans to remind them of their exercises and the correct technique. Patients reported needing to use TRAK with the guidance of their treating physiotherapist initially. Physiotherapists highlighted appointment time constraints and lack of familiarity with TRAK as factors limiting engagement. In Phase 2, 67% patients accessed TRAK outside of the clinical environment. A total of 91% of patients were given a personalised exercise plan, but these were only updated in 34% of cases. Conclusion A comprehensive training package for patients and clinicians has been defined. The refined TRAK intervention is reported using the ‘Template for Intervention Description and Replication in preparation for a definitive randomised control trial

A pilot study of a minimally supervised home exercise and walking program for people with Parkinson’s disease in Jordan

Aim: This study aimed to evaluate the feasibility and cultural considerations of a minimally supervised, home-based exercise program in Jordan. Methods: Quantitative and qualitative approaches were used. Thirty participants were randomly allocated to either an 8-week intervention group (n = 16), or a standard care group (n = 14). The intervention incorporated the home use of an exercise DVD, walking program and initial instructional sessions and weekly phone calls provided by a physiotherapist. Interviews were used to explore feasibility. Unified Parkinson’s disease rating scale (UPDRS-III); balance and walking speed were assessed. Results: The retention rate was 86.7% and mean adherence rate was 77%. Personal and sociocultural barriers of adherence to the exercise program were identified. UPDRS-III at follow-up was lower in the intervention group. Conclusion: A home exercise program was feasible. Sociocultural barriers specific to Arabic culture may affect the uptake of such an intervention in Parkinson’s disease in these countries

Functional magnetic resonance imaging neurofeedback-guided motor imagery training and motor training for Parkinson's Disease: randomized trial

Objective: Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF) uses feedback of the patient’s own brain activity to self-regulate brain networks which in turn could lead to a change in behavior and clinical symptoms. The objective was to determine the effect of NF and motor training (MOT) alone on motor and non-motor functions in Parkinson’s Disease (PD) in a 10-week small Phase I randomized controlled trial. Methods: Thirty patients with Parkinson’s disease (PD; Hoehn and Yahr I-III) and no significant comorbidity took part in the trial with random allocation to two groups. Group 1 (NF: 15 patients) received rt-fMRI-NF with MOT. Group 2 (MOT: 15 patients) received MOT alone. The primary outcome measure was the Movement Disorder Society—Unified PD Rating Scale-Motor scale (MDS-UPDRS-MS), administered pre- and post-intervention “off-medication”. The secondary outcome measures were the “on-medication” MDS-UPDRS, the PD Questionnaire-39, and quantitative motor assessments after 4 and 10 weeks. Results: Patients in the NF group were able to upregulate activity in the supplementary motor area (SMA) by using motor imagery. They improved by an average of 4.5 points on the MDS-UPDRS-MS in the “off-medication” state (95% confidence interval: −2.5 to −6.6), whereas the MOT group improved only by 1.9 points (95% confidence interval +3.2 to −6.8). The improvement in the intervention group meets the minimal clinically important difference which is also on par with other non-invasive therapies such as repetitive Transcranial Magnetic Stimulation (rTMS). However, the improvement did not differ significantly between the groups. No adverse events were reported in either group. Interpretation: This Phase I study suggests that NF combined with MOT is safe and improves motor symptoms immediately after treatment, but larger trials are needed to explore its superiority over active control conditions

Functional Magnetic Resonance Imaging Neurofeedback-guided Motor Imagery Training and Motor Training for Parkinson’s Disease: Randomized Trial

Objective: Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF) uses feedback of the patient’s own brain activity to self-regulate brain networks which in turn could lead to a change in behaviour and clinical symptoms. The objective was to determine the effect of neurofeedback and motor training and motor training (MOT) alone on motor and non-motor functions in Parkinson’s disease (PD) in a 10-week small Phase I randomised controlled trial. Methods: 30 patients with PD (Hoehn & Yahr I-III) and no significant comorbidity took part in the trial with random allocation to two groups. Group 1 (NF: 15 patients) received rt-fMRI-NF with motor training. Group 2 (MOT: 15 patients) received motor training alone. The primary outcome measure was the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale-Motor scale (MDS-UPDRS-MS), administered pre- and post-intervention ‘off-medication’. The secondary outcome measures were the ‘on-medication’ MDS-UPDRS, the Parkinson’s disease Questionnaire-39, and quantitative motor assessments after 4 and 10 weeks. Results: Patients in the NF group were able to upregulate activity in the supplementary motor area by using motor imagery. They improved by an average of 4.5 points on the MDS-UPDRS-MS in the ‘off-medication’ state (95% confidence interval: -2.5 to -6.6), whereas the MOT group improved only by 1.9 points (95% confidence interval +3.2 to -6.8). However, the improvement did not differ significantly between the groups. No adverse events were reported in either group. Interpretation: This Phase I study suggests that NF combined with motor training is safe and improves motor symptoms immediately after treatment, but larger trials are needed to explore its superiority over active control conditions. Clinical Trial website : Unique Identifier: NCT01867827 URL: https://clinicaltrials.gov/ct2/show/NCT01867827?term=NCT01867827&rank=

Exploration of a co-production approach to developing a walking group with people with Huntington's Disease

Background: People with Huntington’s disease (HD) struggle to maintain regular physical activity despite evidence of the benefits of exercise. This study aimed to evaluate the experiences of people who co-produced a walking group for people with HD. Methods: Three people with HD, a specialist HD advisor (sHDA), two project officers from Let’s Walk Cymru (LWC) and the research team co-produced and participated in a walking group for people with HD. A walking group for people with HD was supported weekly by LWC for eight weeks and fortnightly for a further 12 weeks. Semi-structured interviews were undertaken with three people with HD, a sHDA and two project LWC project officers. Interviews were transcribed verbatim and analysed using thematic analysis. Findings: Interviews identified six themes across participants: “organisation and planning”; “purpose of the walks”; “benefits”; “barriers”, “the group” and “the future”. People with HD enjoyed participating in the walks and reported increased confidence to be more active outside the home. All participants noted challenges including apathy, diminished planning skills, social stigma and motor problems specific to HD; people with HD perceived a lack of influence in relation to co-planning and co-execution of the walking group. Conclusions: The walking group was perceived as enjoyable, beneficial, and motivational. This is the first study to report co-production of a walking group with people with HD and the findings suggest that further research is needed to adapt models of co-production for people with a long-term complex condition

Exercise interventions in Huntington's disease: An individual patient data meta-analysis

Background: Physical activity may be beneficial in Huntington's disease, however studies to date have been underpowered to detect change. We combined data from five randomized controlled feasibility trials using individual patient data meta‐analyses. Methods/Design: All trial interventions comprised a combination of supervised and self‐directed physical activity, with varied emphasis on aerobic, strength, endurance, flexibility, and task training. Duration ranged from eight to 16 weeks. The primary outcome was the modified Unified Huntington's Disease Rating Motor Score. Secondary outcomes included the Symbol Digit Modality Test, Berg Balance Scale, 30‐second Chair stand, Timed Up and Go, Gait speed, Physical Performance Test, six‐minute Walk, International Physical Activity Questionnaire, Hospital Anxiety and Depression Scale, EuroQol Health Utility Index, Short‐Form 36 Health Related Quality of Life Scale. The primary analysis employed a two‐stage approach. A one‐stage approach was explored as a sensitivity analysis using a cross‐classified (by study site) linear mixed effects model. Results: 121 participants provided complete data. Risk of bias was moderate; however primary outcomes were blind assessed. Primary pooled effect estimates adjusted for baseline modified motor score (95% CI) were 0.2 (‐2.1 to 2.6) favoring control. There was considerable heterogeneity between the studies. Conclusions: There was no evidence of an exercise effect on the modified motor score in these relatively short duration interventions. Longer duration trials incorporating supervised components meeting frequency, intensity, time and type principles are required. Lack of common outcomes limited the analysis and highlight the importance of a core outcome set for evaluating exercise in Huntington's disease

Physical therapy and exercise interventions in Huntington's disease: a mixed methods systematic review protocol

Review question/objective: : The review seeks to evaluate the effectiveness of physical therapy and exercise interventions in Huntington's disease (HD). The review question is: What is the effectiveness of physiotherapy and therapeutic exercise interventions in people with HD, and what are patients’, families’ and caregivers’ perceptions of these interventions? Review question/objective: The specific objectives are: Review question/objective: This mixed methods review seeks to develop an aggregated synthesis of quantitative, qualitative and narrative systematic reviews on physiotherapy and exercise interventions in HD, in an attempt to derive conclusions and recommendations useful for clinical practice and policy decision-making

Exploring computerised cognitive training as a therapeutic intervention for people with Huntington's disease (CogTrainHD): protocol for a randomised feasibility study

Background Cognitive impairments, especially deficits of executive function, have been well documented as a core and early feature in Huntington’s disease (HD). Cognitive impairments represent considerable burden and can be devastating for people and families affected by HD. Computerised cognitive training interventions that focus on improving executive function present a possible non-pharmacological treatment option. We propose to determine the feasibility, acceptability, and appropriate outcome measures for use in a randomised controlled feasibility study. Methods/design Participants will be randomised into either a computerised cognitive training group or a control group. Those randomised to the training group will be asked to complete a cognitive training intervention based on the HappyNeuron Pro software tasks of executive function, for a minimum of 30 min, three times a week for the 12-week study duration. Participants in the control group will not receive computerised cognitive training but will receive a similar degree of social interaction via equivalent study and home visits. We will explore quantitative outcome measures, including measures of cognitive performance, motor function, questionnaires and semi-structured interviews, as well as magnetic resonance imaging (MRI) measures in a subset of participants. Feasibility will be determined through assessment of recruitment, retention, adherence and acceptability of the intervention. Discussion The results of this study will provide crucial guidance and information regarding the feasibility of conducting a randomised controlled study into computerised cognitive training in HD. This study is crucial for the development of larger definitive randomised controlled trials which are powered to determine efficacy and for the development of future cognitive training programmes for people affected by HD

A randomised feasibility study of computerised cognitive training as a therapeutic intervention for people with Huntington's disease (CogTrainHD)

Background Huntington’s disease (HD) is associated with a range of cognitive deficits including problems with executive function. In the absence of a disease modifying treatment, cognitive training has been proposed as a means of slowing cognitive decline; however, the impact of cognitive training in HD patient populations remains unclear. The CogTrainHD study assessed the feasibility and acceptability of home-based computerised executive function training, for people impacted by HD. Methods Thirty HD gene carriers were recruited and randomised to either executive function training or non-intervention control groups. Participants allocated to the intervention group were asked to complete executive function training three times a week for 30 min for 12 weeks in their own homes. Semi-structured interviews were conducted with participants and friends, family or carers, to determine their views on the study. Results 26 out of 30 participants completed the baseline assessments and were subsequently randomised: 13 to the control group and 13 to the intervention group. 23 of the 30 participants were retained until study completion: 10/13 in the intervention group and 13/13 in the control group. 4/10 participants fully adhered to the executive function training. All participants in the control group 13/13 completed the study as intended. Interview data suggested several key facilitators including participant determination, motivation, incorporation of the intervention into routine and support from friends and family members. Practical limitations, including lack of time, difficulty and frustration in completing the intervention, were identified as barriers to study completion. Conclusions The CogTrainHD feasibility study provides important evidence regarding the feasibility and acceptability of a home-based cognitive training intervention for people with HD. Variable adherence to the cognitive training implies that the intervention is not feasible to all participants in its current form. The study has highlighted important aspects in relation to both the study and intervention design that require consideration, and these include the design of games in the executive function training software, logistical considerations such as lack of time, the limited time participants had to complete the intervention and the number of study visits required. Further studies are necessary before computerised executive function training can be recommended routinely for people with HD