MSIPC-2
Research type
Research Study
Full title
Role of Remote Ischaemic Preconditioning on Activity, Fatigue and Gait of people with Multiple Sclerosis.
IRAS ID
262744
Contact name
KPS Nair
Contact email
Sponsor organisation
Sheffield Teaching Hospitals
Duration of Study in the UK
1 years, 11 months, 30 days
Research summary
Research summary- Regular physical activity has been shown to improve physical fitness, fatigue, quality of life, and reduce the progression of disability in people with multiple sclerosis (MS). However, people with MS are less physically active than the general population, due to both psychological factors such as lack of motivation, self-belief and self-regulatory constructs, and physical factors such as fatigue, weakness, pain and ataxia.\n\nRemote Ischemic Pre Conditioning (RIPC), the inflation of a blood pressure cuff around the arm to temporarily occlude blood circulation, has been shown to improve exercise performance and delay fatigue in athletes. RIPC is a simple and easy intervention which could have a significant impact on physical activity of people with MS. However, there is little to no research examining the effect of RIPC on walking or exercise performance in MS patients. Preliminary studies of ours showed that RIPC is safe and well tolerated by MS patients, and suggested an improvement in distance walked during the 6 minute walk test (6MW), a reduction in perceived exertion after exercise and improved exercise tolerance in MS patients. The aim of this trial is to assess whether RIPC can improve activity, gait and reduce fatigue in people with MS. \n\nParticipants will attend four study visits. They will be randomised to receive either RIPC or a dummy intervention (sham) which they (or their carer) will be taught how to perform and be asked to do so at home every day for six weeks. \n\nPhysical activity, gait and fatigue will be compared before and after the intervention period. Participants will be asked to wear an activity monitor at home for 1 week before and after the intervention to measure levels of activity. To assess gait, participants will complete the 6 minute walk test wearing inertial sensors which measure gait and distance walked. The modified fatigue impact scale will be completed before and after the intervention and levels of exertion recorded after each 6 minute walk test. \n\n
Summary of results- This randomised double blind placebo control trial aimed to assess whether Remote Ischaemic Preconditioning (RIPC) administered at home for 6 weeks benefited people with multiple sclerosis in terms of their fatigue, mobility and quality of life.
We recruited 94 people to the study over a 39 months period beginning in Oct 2019. The study was paused for 12months due to the COVID-19 pandemic. After revealing the group allocations, it was determined that 47 participants were allocated to the active RIPC group and 45 in the sham RIPC group and the follow-up assessments were completed in 32 active RIPC and 38 sham RIPC participants. Reasons for withdrawal included covid pandemic (Sham=4, Active=4), illness (Active=7), pain/discomfort due to RIPC (Active=3), personal reasons (Active=1), too busy (nSham=1), no reason given (Sham=1, Active=2). In addition, 2 people in the Active RIPC arm did not complete the full 6 weeks RIPC due to discomfort but were included in the analysis as completed follow-up assessments.
No statistically significant differences was detected between the two groups for all demographic and disease characteristics examined although the sham group had a significantly longer time since diagnosis. Disease severity was also matched between the two groups (Sham median EDSS = 4.0 [range 1.0 to 6.5], Active EDSS = 3.0 [1.0 to 7.0]).The primary end point of the study was number of participants achieving Minimum Clinical Important Difference (MCID) in the distance walked during 6-minute walk test before and after the intervention (at least 7% increase in distance walked). 10/32 (31.25%) patients in the active RIPC group and 14/37 (37.8%) patients in Sham group achieved this. This was not a statistically significant difference between the cohorts. Also, while no significant improvement was observed in the walking distance for the active RIPC group with use of 6week RIPC use, the Sham RIPC cohort did show an improvement.
Other outcomes of interest included the change of heart rate and resting Systolic Blood Pressure (SBP) and the reported exertion level (Borgs’ Rating of Perceived Exertion, RPE). Significant differences were observed in the change of heart rate and resting SBP in the active RIPC group within the randomisation visits. This could indicate an improvement in stamina with RIPC use. However, these changes did not persist after 6 weeks of RIPC use. There was also no significant improvement in reported exertion or the change in blood pressure. Meanwhile, the Sham RIPC cohort also exhibited changes in walking distance with 6 weeks intervention and improved exertion indicating a potential placebo effect.
In exploring the patient reported outcomes data, we looked into the number of participants that met the MCID thresholds for fatigue (Modified Fatigue Impact Scale), walking disability (MS walking scale) and quality of life (EQ5D index). There was also no difference in response rates between cohorts. Further, both cohorts reported similar patterns in responses to the patient reported outcomes with both cohorts indicating improved responses at follow-up and worsened quality of life. No statistical differences were observed between cohorts in these outcomes.
With regards to patient safety and tolerability, discomfort scores were significantly higher within the active RIPC cohort compared with the Sham RIPC cohort. Meanwhile, 93.6% and 82.2% of all randomised participants reported any AE within the study period in the active and sham RIPC groups respectively. Skin markings (temporary redness, blueing or pale discoloration), tingling and pins and needles (in the hand and fingers) were reported most commonly in both groups and more prevalently in the Active RIPC group. Pain during the intervention caused a pause or stop in 4 participants in the Active RIPC group.
Taken together, the results of this study indicate that no meaningful improvement in the factors measured was observed for the Active RIPC cohort compared with the Sham RIPC cohort with 6 week use of Remote Ischaemic Preconditioning. Considering the lack of efficacy and the level of discomfort experienced by some of the participants in Active RIPC cohort, this cannot currently be recommended for routine use in this population.
Further study exploring whether longer term use of RIPC might have beneficial effects since other studies have implemented RIPC in other populations over longer periods of time. This study was greatly impacted by the Covid-19 pandemic as the study paused for 12 months which led to participant withdrawals. Investigation of autonomic dysregulation could also be of interest in further study of RIPC in people with multiple sclerosis due to its prevalence in this cohort which could hamper our findings.
The walking tests conducted during this study were instrumented using wearable inertial sensors and a subset of participants completed at-home mobility monitoring using a similar device. This data is yet to be statistically analysed so further work is planned to investigate the impact of RIPC on participants walking gait and mobility performance in their daily lives. This will explore whether subtle changes in gait quality or volume of physical activity occurred due to RIPC use.
REC name
Yorkshire & The Humber - Bradford Leeds Research Ethics Committee
REC reference
19/YH/0187
Date of REC Opinion
3 Jun 2019
REC opinion
Favourable Opinion