Read the interview with study lead, Prof. Clague-Baker
Charlotte Stephens, Research Correspondent, ME Association.
Introduction
We are excited to announce the funding of a new research study that will examine the feasibility of measuring various physiological data during daily activity in people with Myalgic Encephalomyelitis/Encephalopathy (M.E.).
Funding for this new study has come from the MEA Ramsay Research Fund. It represents the first research of its type to be conducted in the UK.
The study is titled: “Feasibility of investigating oxygen consumption (VO2), Heart Rate, Blood Pressure, lactic acid levels and activity levels of people with ME during normal daily activities.”
The research will be led by Dr Nicola Clague-Baker, an Associate Professor of Physiotherapy and lecturer at the University of Leicester.
Recruitment has been delayed because of the Covid-19 pandemic, but is expected to begin by the end of this year or early in 2021. Participants will be recruited online once ethical approval has been granted.
Dr. Clague-Baker also treats patients with neurological problems privately. Her interest in M.E. started over 30 years ago when her best friend developed the condition.
We are very pleased to be able to announce ME Association funding for the first M.E. research project to be carried out here in the UK that involves CPAT (an adapted form of cardio-pulmonary exercise testing) and other measures of activity, that will take place in patent’s homes.
We have been working with Professor Clague-Baker and others from Leicester and Oxford Universities, who will be carrying out this new research, for some time. And, we are very confident that the research, which will record physiological measurements during everyday activities, will provide important new information on muscle, heart, and lung function in people with M.E.
As many people will already know, Professor Mark VanNess and Dr Betsy Keller in America have been involved in CPET research for several years. However, their findings have largely been ignored or even dismissed by the UK medical profession.
Their research has determined important physical abnormalities in people with M.E. that can be used to help to confirm a diagnosis.
It has also confirmed a physiological basis to activity-induced fatigue and post-exertional malaise which has nothing to do with deconditioning, and that graded exercise therapy is not therefore an appropriate form of management in M.E.We are very grateful for input from Professor Mark Van Ness during the preparation period and to Dr Betsy Keller for agreeing to be involved with the actual study.
More details on patient recruitment will follow once the Covid-19 lockdown has been lifted.
Dr Charles Shepherd, Hon. Medical Adviser, ME Association
Dr Clague-Baker is an active member of Physios for M.E. and in 2019 with fellow members, Natalie Hilliard, Dr. Michelle Bull and Karen Leslie, set out to improve the knowledge of M.E. in physiotherapy practice.
As they worked on their social media and website material, they became more aware of M.E. research and determined those areas they could build on to increase understanding of the condition and its management.
As a result, they put together this research study with the help and support of Professor Sarah Tyson from the University of Manchester and Professor Helen Dawes from Oxford Brookes University.
Dr Betsy Keller from Ithaca College in New York who has worked on CPET studies in M.E. (and with The Workwell Foundation) that helped determine abnormalities relating to exercise, energy production and lactic acid, will also provide some help with the study.
Cardiopulmonary Exercise Testing
Cardiopulmonary exercise (CPET) studies from the Workwell Foundation and others in America have determined that people with M.E. have an abnormal aerobic metabolism (problems converting food into energy using oxygen) when at maximum exercise capacity.
They found low levels of VO2 (oxygen uptake in the body) and greater levels of lactic acid during exercise when performed on an exercise bike under laboratory conditions.
However, it has not been determined if these abnormalities occur at normal levels of activity, such as during daily activities like washing, dressing, and moving about etc. which is what this new study will aim to discover.
Study Details
The study will be carried out on 15-20 adults with M.E. of differing severities (mild to severe) over the course of 7 days. During this time, various physiological responses will be measured and recorded during everyday activities completed in their homes.
The participants will wear a portable VO2 system during some activities, as well as a heart rate monitor and an accelerometer continuously throughout the day. In addition, lactic acid levels and blood pressure will be taken regularly throughout the study period.
Various questionnaires and scales will also be completed, to gauge symptom severity, activity levels and PEM (Post-exertional malaise) and correlate these with the physiological data. The participants will then give feedback at the end of the study as to whether they were able to wear and tolerate the equipment for this prolonged period.
The main aim of this study is to explore the acceptability and feasibility of the testing protocol (to see if patients can cope with the measuring devices and that it is an effective way of collecting data).
If it is successful, applications will be made for the funding of larger studies, which will indicate whether it may be possible to develop a diagnostic test using this protocol.
Additionally, the data could be used to validate the use of heart rate monitoring as an intervention to pace activity and prevent or minimise PEM.
Ultimately, this study protocol could be used as a gentler alternative to cardio-pulmonary exercise testing for studying and potentially diagnosing people with M.E. as many people with the condition are reluctant to undertake cardio-pulmonary exercise due to the risk of triggering a deterioration of their condition.
Interview with Dr Nicola Clague-Baker (Study Lead)
1. Can you briefly explain what this study is hoping to achieve and how any subsequent research that builds on it might add to our knowledge about M.E.?
This study is a feasibility study that will determine if it is possible to carry out a larger study on this topic. It will establish the acceptability of the testing protocol for people with different levels of severity; assess recruitment rates; determine the outcome measures and monitor any adverse events.
With this knowledge, we would hope to apply for funding from the National Institute of Health Research (NIHR) in the UK and/or other funders to determine the oxygen consumption (VO2), Heart rate, blood pressure, lactic acid levels and activity levels of people with M.E. during normal daily activities.
This is important because we know that when people with M.E. exercise to their maximum levels: they have abnormally low levels of VO2 maximum scores; they reach their anaerobic thresholds quicker; they are slower to recover than healthy controls; they produce greater levels of lactic acid when exercising and they have an impaired capacity to recover from this acidosis.
However, we don’t know what happens during normal everyday activities. Some people with M.E. think that they are reaching their anaerobic threshold during normal daily functions which is leading to increased acidosis.
If we can verify this, then it may be possible to develop a diagnostic test involving non-maximal exercise testing and to validate the use of heart rate monitoring (to stay within the anaerobic threshold) as an intervention to pace activity and help prevent or minimise Post-Exertional Malaise (PEM).
2. How does the portable VO2 system work?
VO2 measurements record the amount of oxygen uptake in the body. It relies on healthy lungs to take in oxygen and transport it to the blood, an effective circulatory system to take that oxygen to the muscles, an effective system to transport that oxygen in to the muscles and finally healthy mitochondria to use that oxygen to produce energy.
The greater the VO2 at maximum exercise capacity, the healthier the body. VO2 is measured using a mask that can measure the amount of oxygen that is taken in and the amount of carbon dioxide that is breathed out. Normally this is attached to a non-portable system and a participant runs on a treadmill or cycles and the mask analyses the oxygen intake and carbon dioxide output.
A portable system allows us to go to the participant and measure their oxygen and carbon dioxide levels in their own environment.
This is important especially when researching people with M.E., many of whom are house- or bed-bound or are unable to exercise even in a laboratory.
There are difficulties with portable systems, the main one being the connection between the mask and the analyser which relies on Wi-Fi availability. This is one of the aspects we will be checking in the feasibility study.
Also, the masks have to fit quite tightly on the face and the analyser fits like a small rucksack on the back so we need to see if people with M.E. can manage this, especially those who are severely affected.
3. How and when will you be taking the lactic acid measurements?
The idea is to take the lactic acid measures using a lactic acid monitor, a little like a blood sugar monitor. This will mean pricking the finger, so we will need to work out exactly when to take these measures as we don’t want to be pricking fingers too many times.
This again is part of the feasibility study – is it feasible to prick the fingers of people with M.E. particularly those who are severely and very-severely affected? And, if so, how often can it be done without it causing a problem.
I would hope to take the lactic acid levels at the start of the testing and after each activity e.g. after getting dressed, after walking downstairs, after having a wash etc., but this might not be possible.
I was also hoping to leave the monitor with the participants so they can measure their lactic acid levels over a week. Again, we don’t know yet how often this might occur as some people will be able to cope with it and some will not.
It is also unclear at this point how accurate these measurements will be as lactic acid levels can be taken in different ways e.g. arterial, venous, and even cerebrospinal fluid and the fingertip method might not be as accurate.
4. Why did you choose not to have a control group? What will you be comparing the data against?
We did consider a control group but, as this is a feasibility study, it was not felt to be necessary to compare to controls in this study. There are also published values for VO2 during normal everyday activities in healthy individuals which we can compare to.
It might be that we will have time to do some tests with healthy individuals as comparators and we will apply for ethical approval to do this just in case. When we have completed this study and move on to a larger version that will be more definitive, there will be a control group so that we can be certain how people with M.E. compare to healthy control (even perhaps sedentary or other disease groups) participants.
5. What do you hope to find out from the results?
It would be wrong of a researcher to set out to look for something. We are just trying to understand what is happening to people with M.E. during routine everyday activities.
It might be that they are reaching their anaerobic threshold even at low levels of activity, it might be that their lactic acid levels have a correlation with PEM, it might be that their HR and BP show abnormal responses to activity or it might be that we don’t find anything at all.
We just don’t know and that’s why we need to do this kind of study.
6. What are your next steps following on from this study?
As this is a feasibility study, we will be looking to apply for funding from the NIHR or similar funding body to measure more people so the results can be regarded as definitive.
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