1. Pilot RCT evaluating the AMPCARE Effective Swallowing Protocol (ESP™)
A new treatment protocol for swallowing difficulties following Stroke.
Dr Sue Pownall, Lise Sproson, Professor Pam Enderby, Dr Jenny Freeman
Hello- Good afternoon everyone. I would like to thank the TSHA Committee for the opportunity to present our work to you today, and also to all of you for coming to hear this presentation . I will be talking with you about a new treatment protocol which has been specifically developed for the treatment of persistent swallowing problems post stroke, i.e. those which have persisted for one month or longer beyond the onset of stroke.
Lise Sproson,
Sheffield Teaching Hospitals NHS Foundation Trust 

2. The Research Team
I am honoured to be presenting to you today on behalf of our research team: – anti-clockwise from the top left: Dr. Sue Pownall, Professor Pam Enderby, our statistician Dr. Jenny Freeman – and myself. We are all based in Sheffield, in the North of England. I would also like to acknowledge Russ Campbell and Rick McAdoo, based here in the States who are with us this afternoon and who developed this treatment protocol. Between us I hope we will be able to answer any questions you may have at the end of the session.

3. A taste of Yorkshire
So, just before we begin, I thought I would give you a little taste of some of the things we are famous for in Yorkshire– Henderson’s Relish, a spicy sauce we like to put in stews and steak pies, Yorkshire tea – by appointment to the Queen (who loves a “proper brew” Yorkshire puddings which we like to have with roast beef – and our beautiful Yorkshire Dales countryside. I hope the sheep can read so that he knows that animals need to go right to avoid getting their feet stuck in the cattle grid!

4. Aims of this presentation
To explain what this new treatment protocol entails
To describe how we have evaluated its treatment efficacy, when compared to usual care
To share with you what we found
Ok, so I am here today to tell you about an exciting new treatment package – the AMPCARE Effective Swallowing Protocol – or Ampcare ESP . This is a NEW approach to transcutaneous electrical stimulation. It is different from the e-stim approaches which you may have used or read about before in the research literature so far, and we have just completed a multi centre, randomised controlled pilot study in the UK in order to evaluate its treatment efficacy. I would like to outline for you what the treatment package involves and then to present our study findings.

5. Dysphagia care in the UK
There is much variability in dysphagia care in the UK
In some areas, treatment involves exercise programmes for swallow rehabilitation - but not on an intensive basis
In some areas, it involves management of symptoms only (e.g. modified food/drink consistencies, adaptive postures)
Our professional body does not currently support the routine use of electrical stimulation, due to conflicting evidence from previous research studies
To give a little context to our study, In the UK, as you know, healthcare is funded by the National Health Service –which means we have no insurance component to health care delivery. That being the case, we still have much variability in the way Stroke services are provided in different areas of the country. Stroke patients are admitted to acute admission wards and then transferred to specialist Stroke Units depending on bed availability. Once medically stable, they are then discharged either to rehab units in the community, or if well enough, to their own homes where they receive rehab visits. This period is the one in which most variability occurs – in terms of the overall length of rehab . This can vary from 6 weeks to several months. SLTs manage dysphagia at all stages but we are currently not resourced to see people intensively, so in many areas, SLT input for dysphagia involves management of symptoms, for example recommendations regarding modified diet and fluids, postural strategies and some dysphagia therapy exercises. We are currently not permitted to use electrical stimulation outside of a research setting, as our professional bodies have called for further research in order to clarify the evidence before brining electrical stimulation into mainstream practice. This is the approach we would take with any new drug or therapy.

6. Rationale for our study
Literature reviews have shown some promising evidence for the use of electrical stimulation – however results were conflicting
We were keen to find clearer answers about this potentially promising approach to:
improve swallow function rather than
manage dysphagia symptoms
Literature reviews on transcutaneous electrical stimulation for post stroke dysphagia have presented us so far with very conflicting results. We are keen therefore to try and clarify how well this new treatment approach might work, so that we might have more rehab tools at our disposal to improve swallow function, rather than merely to manage dysphagia symptoms.

7. AMPCARE Effective Swallowing Protocol
Package of 3
potentially active
components
Electrical
Muscle
Stimulation
Resistive
Laryngeal
Exercises
Intensive
Treatment
Schedule
The Ampcare Effective swallowing protocol (or Ampcare ESP) has three main components, as shown here:1) Electrical transcutaneous muscle stimulation,2) 3 specially selected exercises, involving the use of resistance - and 3) an intensive therapy approach – we saw patients in the treatment arm each weekday for a 4 week period. This protocol uses newly designed electrodes, new treatment parameters and a specially designed resistance device. I will tell you more about each component in details as we continue. We are aware that this is a what the literature might term a “complex intervention” – i.e. it has 3 components – any one of which might be considered active in its own right – however we wanted to look at the effect of the treatment protocol as a whole – since the 3 components were designed to work synergistically. Our approach is therefore pragmatic, we are keen to find out how the protocol works as a whole, and to know whether it can deliver better patient outcomes than any of the traditional dysphagia therapy interventions employed currently in the UK.

8. Rationale for electrical stimulation
The rationale for this technique and parameters follow the rules of electrophysiology for stimulating small muscle groups.
Chronic illness and decreased physical activity leads to muscle weakness or disuse atrophy.
Slower and weaker muscle movements can alter timing/force/coordination of swallow.
This treatment protocol was designed by specialist physio and speech and language therapists and it is based on the scientific principles of muscle training and re-education and also of electrophysiology. It is also derived from the rationale that we know that chronic illness and disuse lead to muscle atrophy and also that slower and weaker muscle movement during swallowing can lead to increased risks of laryngeal penetration and aspiration.

9. Electrical Stimulation – principles
NMES definition: “the external control of innervated but paretic muscles by electrical stimulation of the corresponding intact peripheral nerves” (Huckabee and Doeltgen 2007).
Principles of electrophysiology for small muscle groups:
low levels of stimulation produce sensory feedback
increased current amplitude or pulse duration will produce muscle contraction
NMES – or neuromuscular electrical stimulation, is defined here by Huckabee and Doeltgen – in other words, the stimulation can produce activity in paretic muscles by stimulating their associated nerves. The principles of electrophysiology which are relevant here are that – with low levels of stimulation, you will achieve sensory feedback to the brain and with increased current intensity, you will get muscle contraction This is achieved by the current changing the polarity of the nerve endings at the neuromuscular junction.

10. Why use electrical stimulation to treat dysphagia?
Reduced or delayed hyo-laryngeal elevation is a common cause of dysphagia & aspiration (Burnett 2003).
It has been hypothesized that electrical stimulation can assist hyo-laryngeal elevation (Freed 2001, Leelamanit 2002, Permsirivanich, 2009, Gallas, 2010).
Stimulation of laryngeal elevation musculature via NMES in combination with traditional treatments is suggested to re-educate these muscles (Lim 2009, Park 2012, Kushner 2013, Lee 2014)
The treatment protocol specifically targets the suprahyoid muscles, since we know that reduced laryngeal elevation is one of the most commonly experienced symptoms of dysphagia. Here I have summarized for you some of the published literature to date which has found positive effects of electrical stimulation – it should be noted that some other studies (for example a trial by Bulow) have not been able to replicate this effect. We should also note that that these studies were reporting a different e-stim approach to the one used in this study. We were keen to try the new electrodes and treatment parameters and see how our results compared with the results achieved with the earlier approaches.

11. Does electrical stimulation work in the treatment of dysphagia?
NMES has been used on other muscle groups for some time
There are well established clinics in the NHS in the UK which use electrical stimulation to treat foot drop
Due to controversy about the efficacy of NMES in treating dysphagia – it is not currently used in this way in the UK
Currently in the UK, we have routine clinical use of electrical stimulation only for some applications – for example by physio’s to treat foot drop and facial palsy, however there is much research underway in the Uk and in Europe to investigate both electrical and magnetic stimulation, for example stimulation of the tibial nerve to treat incontinence, and the use of direct stimulation to the cortex with electrical and magnetic stimulation to treat dysphagia and aphasia. Studies are also underway to investigate stimulation delivered inside the pharynx, via adapted NG tubes.. These uses of stimulation and also the use of e-stim for dysphagia are not currently supported by the Royal College of Speech & Language Therapists as they have called for further research in order to clarify guidance for clinicians.

12. The call for robust research in this area
Burns and Miller (2011) reviewed the evidence on the effectiveness of NMES. They included 14 studies which all indicated positive effects of NMES, but found the studies were not robust, few in number and omitted longer term follow up.
A call for more robust research has also been made by Carnaby-Mann & Crary (2007), Clark et al (2009) & in the Cochrane Systematic Review by Geeganage et al (2012).
Review of the published literature to date clearly illustrates the need for large scale, randomized trials in order to provide clearer answers. Virtually all of the systematic reviews which have been completed to date comment upon the difficulty in combining studies to gain a clearer overall view,due to the fact that the studies all use different treatment parameters and electrode placements and many lack randomized controls as a comparator. This makes meta-analysis challenging, due to this heterogeneity of approaches. Repeated calls have therefore been made for large scale, randomized controlled trials. Examples of this include Mann and Crary, Clark et al and the Cochrane Database systematic review which was lead by Geeganage in 2012.

13. Steps in designing robust research
Full scale study
Pilot study
Feasibility Study
We wanted to take on board the criticism of earlier literature for not taking a robust enough approach to research. Our approach has therefore been to move systematically from the research question, via feasibility and pilot study stages, through to a full scale trial – if of course the pilot study results showed strong enough results to justify this.
Research Question

14. Feasibility Study
AMPCARE ESP™ was carried out on a case series of 5 participants
All 5 showed improvements in their swallowing
2 participants returned to full oral diet having been on PEG feeding for months
3 participants were able to increase the amount and range of food consistencies, although they continued to receive their main nutrition via PEG
We began with a feasibility study in 2011, on a case series of 5 patients. This was a mixed group – including patients with dysphagia due to Stroke, PD and Cancer. The patients all received the Ampcare ESP treatment – which I will describe for you in further detail in just a moment. We found that all of the patients made progress, but the strongest progress was made by the 2 Stroke patients, who returned to full oral diet – having been PEG fed for between 5 and 24 months. We therefore selected Stroke as a population for the next phase of the research – the pilot study.

15. Pilot Study Study design – a multi-centre RCT on 30 participants
Comparing:
Usual UK dysphagia care
AMPCARE Effective Swallowing Protocol (ESP™)
Outcome Measures included:
FOIS (functional oral intake scale)
Videofluoroscopy – blinded assessment using Rosenbek PAS scale
Tolerability and SWAL-QoL questionnaires
The pilot study which I would like to share with you today, involved a multi centre, randomized trial of 30 patients, 15 patients were randomized into the usual care arm, and 15 into the intervention or Ampcare ESP arm. We selected patients who were at least one month post onset of stroke as we wanted to control for effects of spontaneous recovery or response to traditional therapy in the more acute phase of stroke. There was no upper limit on time post stroke for inclusion in the study – the greatest time post onset was 73 months. Our study therefore focuses on more persistent dysphagia. We also selected patients who were experiencing reduced laryngeal elevation as one of their dysphagia symptoms, as this was the area of function we wanted to improve – and in doing so, to improve overall swallow safety. Reduction in laryngeal elevation was therefore checked at baseline, prior to randomisation. Our outcome measures included the Functional oral Intake scale – as a pragmatic measure of patients ability to eat and drink, the Rosenbek Penetration-Aspiration scale, which gave us an objective measure of safety in swallowing, which was completed by a blinded assessor in order to avoid bias. We also included tolerability and SWAL-Qol questionnaires to gain feedback from the patients about their experiences during treatment and a patient reported outcome measure of swallow related quality of life.

16. AMPCARE Effective Swallowing Protocol
Package of 3
potentially active
components
Electrical
Muscle
Stimulation
Resistive
Laryngeal
Exercises
Intensive
Treatment
Schedule
As shown earlier in the presentation, the Ampcare Effective Swallowing protocol contains 3 main components, electrical stimulation, exercise against resistance and intensive treatment each weekday for 20 sessions. I will now describe each of these components in turn.

17. Component 1: Electrical Stimulation
Here you can see the shape of the new electrodes - these were designed specifically to target the suprahyoid muscles. We were particularly targetting the geniohyiod, the mylohyoid and the anterior belly of the digastric muscles. The Ampcare electrodse contain fanned electrode wires, silver printing and carbon film in order to disperse the current evenly over the target area. The electrodes are connected to the stimulation unit, which has several pre-programmed settings but which also has the facility to adjust current intensity throughout treatment sessions, in order to provide maximum therapeutic gain, while working within each patients individual tolerance levels. The level of current can therefore be adjusted within and across therapy sessions, as patients become accustomed to the sensations, gain confidence and can therefore tolerate higher intensities.

18. Dispersion test results
Dispersion test to check the uniformity of current distribution
AMPCARE’s E Series Electrode:
Electrical stimulation occurs evenly across surface of electrode, resulting in a more comfortable treatment
Standard Electrode:
Electrical stimulation occurs primarily in the blue "Hot-Spot" area, resulting in a painful stimulus
Here you can see the results of dispersion tests of two types of electrodes in order to illustrate the impact of electrode shape and design upon stimulation delivery. You can see on the top picture the even dispersion of the current in the Ampcare electrodes, shown by the even green shading, compared to the hot-spots (shown on the lower picture in blue) that standard electrode designs can produce, particularly at higher intensities. This even dispersion of current means that the sensations are more comfortable for patients, thereby enabling them to engage more fully with the exercises, to complete the full course of treatment and to tolerate higher currents, producing stronger muscle contractions and therefore greater potential treatment outcomes.
Images Courtesy of Ampcare LLC

19. Effects of Ampcare stimulation on VF
In this slide, you can see the effects of the stimulation on hyoid elevation under videofluoroscopy. Note the elevation of the hyoid in the VF image on the right of the slide, which was taken while stimulation was on. Since we know that hyoid elevation impacts upon the degree of laryngeal elevation, this shows how stimulation can be used synergistically with many of the laryngeal elevation exercises we use within traditional dysphagia therapy. These slides were the stimulus for our team in the UK to begin work with the team in the States to test out their protocol in order to see whether we could achieve similar results.
Images Courtesy of Ampcare LLC

20. Procedure
Stimulation was given in 5 second pulses, and sessions lasted for 30 minutes
10 minute blocks of 3 swallowing exercises
Current intensity increased at each change of exercise as tolerated by participant
Pulse rate = 30Hz, to produce muscle contraction while avoiding fatigue/spasm
Waveform = symmetrical, biphasic, both electrodes are active, allowing stimulation of paired
muscles
The patients in the intervention group received stimulation in 5 second pulses, throughout each 30 minute session. Sessions took place each weekday, Monday to Friday for a total of 20 sessions. Participants were offerred a choice of receiving treatment in their own home or in an out-patient department. We found that all patients selcted to receive treatment in their own homes. During each 5 second pulses of stimulation, patients were encouraged to perform specified therapy exercises , and to rest in between until the next pulse. Sessions involved minute blocks and after each 10 minute block, participants were asked whether they could tolerate a stronger current. This is because larger current produces a stronger muscle contraction. A pule rate of 30HZ was used, to provide visible muscle contraction while avoiding muscle fatigue or spasm. Both electrodes are active, in order to permit stimulation of paired muscle groups.

21. Procedure Exercise and NMES Duty Cycle Progression
Week 1 – Duty cycle will be 5 seconds on and 25 seconds off for a total of 60 stimulations
Week 2 – Duty cycle will be 5 seconds on and 20 seconds off for a total of 72 stimulations
Week 3-4 – Duty cycle will be 5 seconds on and 15 seconds off for a total of 90 stimulations
The intervention group involved 20 sessions of treatment, given over a 4 week period. This slide shows how the rest period between pulses of stimulation was gradually reduced over consecutive weeks, so that patients moved from producing 60 swallows per session in the first week to 90 swallows per session in the third and fourth weeks. The control group received usual dysphagia care. As this was a multi-centre study, therapists were permitted to deliver whatever interventions they would normally, as we wanted to see how the intervention arm compared to usual UK dysphagia care.

22. Component 2: Laryngeal Exercises
Exercise 1 – Chin to chest + Effortful swallow
Exercise 2 – Chin to chest + Mendelsohn manoeuvre
Exercise 3 – Chin to chest + Jaw open/close + Effortful swallow
All against resistance -
provided by a new,
specially designed brace.
In the intervention group, during each 5 second stimulation pulse, patients were encouraged to perform these exercises, beginning with 10 minutes on exercise 1, chin to chest plus effortful swallow – through to exercise 3, chin to chest, jaw open and close followed by effortful swallow. This slide also shows the neck brace device – specially designed to provide resistance for the chin to chest exercises. You may be familiar with some of the recent literature (eg Watts 2013 and Yoon 2014) which showed greater muscle activity from chin tuck against resistance when compared to the Shaker manoeuvure.

23. Component 3: Intensive Treatment
Treatment is given for:
30 minutes per day
each weekday
for 20 treatments (approximately 4 weeks)
So – this was quite an intensive regime – I am not sure whether this cartoon represents the therapist or the patients! However, although we lost some patients to follow up – one patient due to other medical conditions, two patients who unfortunately passed away and and a couple who declined their follow up VF, we had no drop out from treatment sessions. In fact data from the tolerability questionnaires told us that the patients liked the feeling that they were working hard as they felt it was doing them good.

24. The 3 components working together
I would now like to show some video clips, to demonstrate how the treatment components work together.

25. Results - FOIS FOIS: End of treatment:
50% of usual care group improved, compared to 62% of
the intervention group.
FOIS: 1 month follow up:
57% of usual care group improved, compared to 75%
of the intervention group.
So – onto the results. To orientate you to this slide, the usual care group is shown in red and the Intervention group is shown in blue. The graph on the left shows the percentage of patients in each group who either got worse, stayed the same, or made progress by the end of the treatment month. We found that significantly more patients in the intervention group improved on the functional oral intake scale, compared to the usual care group. One example to illustrate this is a gentleman who had been NBM and PEG fed for 3 months following his stroke. At the end of 20 treatment sessions, he was able to safely manage fork-mashable diet and coating (nectar) fluids – and to enjoy a Christmas dinner with his family. You can also see here that some of the usual care group (shown in red) got worse, whereas none of the intervention group got worse. We also gathered data on functional oral intake one month later – in order to check the longer term outcomes of treatment. These results are shown on the graph on the right. We found that, not only were the initial treatment effects stable, but patients had continued to make improvement after treatment had ended, and that this was particularly true for patients in the intervention group (again shown in blue). We also wanted to find out the degree of progress each group had made. Prior to the start of the study, we determined that a one point change on the FOIS scale would constitute clinically meaningful change. We found that the usual care group improved by a mean of 0.5 points and the intervention group by a mean change of 2 points – i.e. clinically significant and meaningful change.

26. Results - Rosenbek Rosenbek:
Usual care: 50% improved with fluids & 17% on diet
Intervention: 58% improved with fluids & 67% on diet
These graphs show changes made on the Rosenbek penetration- aspiration scale. This outcome measurement was made by an assessor blinded as to which group each patient was in, in order to avoid bias. The graph on the left shows changes regarding diet and the graph on the right, changes with fluids. The control group are shown in red and the intervention group in blue. Again we found that both usual care and intervention groups improved, but again a greater percentage of the intervention group improved. This effect was especially marked with diet. Again, while some of the usual care group had got worse on both diet and fluids, none of the intervention group got worse . If we look at the graph on the left for a moment, you can also see here that the majority of the control group appeared to have stayed the same as regards diet – analysis of individual results however suggests that this was due to a ceiling effect – a greater proportion of the control group were less severely dysphagic and so had less progress to make with diet. We were unable to stratify participants by initial dysphagia into matched groups due to the restricted sample size numbers at this pilot stage. It is interesting to note however, the skew towards more severely dysphagic patients in the intervention group, as this further supports the trend towards efficacy of the intervention, since greater progress was even though this group included patients who were initially more severely dysphagic. Analysis of initial FOIS scores showed that 7 of the intervention group had initial FOIS scores of 2 or below, whereas only 4 of the control group had scores of 2 or below. This was also the case with the initial Rosenbek scores – 12 of the intervention group had initial scores of 6-8, indicating aspiration, compared to only 7 members of the control group.

27. Results – SWAL-QoL SWAL-QoL:
Usual care: 39% reported improved quality of life by end of
treatment & 42% at 1 month follow up.
Intervention: 83% reported improved quality of life by end
of treatment & 100% at 1 month follow up.
The SWAL_QOL (swallow related quality of life) data illustrates how much patients themselves felt that the treatment had worked. The graph on the left shows patient rating of swallow related quality of life immediately after treatment. The vertical axis shows the patients’ ratings out of a maximum score of 100%. You can see significantly fewer of the intervention group (shown in blue) felt less happy about their swallow after treatment compared to the usual care group. We know from experience that it is not uncommon for some patients to feel less satisfied about their swallow immediately after treatment – this can be due to increased awareness of their difficulties, or frustration at modifications to their diet and fluids.You can also see that the intervention group achieved the highest patient QOL ratings. Looking now at the graph on the right, you can see that improvement in patient ratings of swallow related quality of life were not only maintained but extended after treatment, as we found that patients continued to make progress after treatment. finished. This effect is hugley significant in the intervention group at one month after treatment (again shown in blue)

28. Patient & Carer feedback
Patient feedback: “I feel better at swallowing – no problems swallowing at all now.” “I thought the treatment was very good and I would recommend it to anybody.” “I’ve enjoyed taking part. It’s given me a positive feeling about my swallow.”
Carer feedback: “He can drive short distances now without having to pull over to use the pot.” “He sleeps through the night now without waking up coughing.” “She’s definitely not coughing anywhere near as much now.”
These are some quotes from our intervention group about the effective swallowing protocol. One gentleman who had initially been unable to manage even his saliva and so was woken up several times throughout the night needing to expectorate, found a hugely significant benefit from being able to sleep throughout the night. This was a finding which is not captured from the standardised scales, but as I am sure you will appreciate, was much valued by him and by his wife.

29. Limitations
This was a pilot study – therefore sample sizes are not large enough at this stage to show statistical significance, however they have shown clinically meaningful change
The outcome measures which were used were relevant and captured change, however it may be useful to also include a measure of some physiological changes – e.g. laryngeal elevation.
It was not possible within the sample size to match for initial dysphagia severity, with more severe patients in the intervention group. Larger sample size in the full scale trial should balance this effect.
Our current study was at pilot scale – therefore our sample size for this phase is not large enough to fully determine statistical significance, however our statistician advises that the results show strong positive trends and justify progression to a fully powered trial. Also, while the outcome measures we used proved to be specific and sensitive enough to capture change, we feel that it may also be useful to include a measure of physiological changes – eg hyo-laryngeal elevation, and possibly also the effects of treatment on reduction of pharyngeal residue . We therefore plan to use some of the newer software applications such as ImageJ and MorphoJ to analyse this. Finally, although we were unable to match across groups for initial dysphagia severity due to the small sample size, we expect that during the fully powered trial of 220 patients, the sample size will be great enough to balance out the groups.

30. Conclusions No adverse events occurred during 295 interventions –
the treatment is safe and tolerable
The pilot study findings justify progression to a fully
powered trial
We have piloted the outcome measures successfully
Based on the findings from the pilot results, power
calculations indicate we will need around 220 participants
for the full scale study, involving around 12 UK sites
In conclusion from our pilot study, we found the treatment to be safe and tolerable for patients. There were no adverse events during 295 treatment sessions. Our results have displayed clinically meaningful change, justifying progression to a fully powered randomized controlled trial. Sample size calculations on this data suggest that this trial would need to recruit around 220 patients in order to confidently determine statistical significance. We are currently in the process of bidding for funding to undertake this work.

31. Acknowledgements
The study team; Dr Sue Pownall, Lise Sproson, Professor Pam Enderby and Dr Jenny Freeman gratefully acknowledge funding for this study from:
We would like to acknowledge funding for this pilot study from these organizations.
NIHR CLAHRC
for South Yorkshire

32. Thank you for your attention – do you have any questions?