(Oxford,UK) Recruiting: A study looking into energy status & MRS in CFS

Dolphin

Dolphin

Senior Member (Voting Rights)
via https://cfsme-registry.info

[2018-02-23] Energy Status and MRS
Part 1 of this document explains the purpose of this study and what will happen to you if you take part.
Part 2 gives you more detailed information about the conduct of the study.



PART ONE

What is the purpose of the study?



Chronic fatigue syndrome (CFS) can be very disabling for sufferers but the search for better treatments is handicapped by lack of knowledge about the brain biochemistry that underpins important symptoms such as exhaustion, poor memory and concentration and impaired sleep.



Advances in magnetic resonance imaging (MRI) mean that it is now possible to measure brain structure and function non-invasively. Magnetic resonance spectroscopy (MRS) is a form of MRI which is able to measure brain biochemistry and we have access to a new, advanced MRS system at the John Radcliffe Hospital at the Oxford Centre for Functional Imaging of the Brain (FMRIB) (www.fmrib.ox.ac.uk). The aim of this pilot study is to use this new MRS system to examine brain chemicals in people with CFS, focusing particularly on a chemical called lactate which is involved in energy production in cells and which can be measured with modern MRS systems.



Research studies have also noted a relationship between the immune system (how the body reacts to an infection) and the development of mood symptoms. For this reason we wish to take an optional blood sample.



Participants

We are asking you to participate as someone who has a history of CFS. Altogether we plan to study 12 people with CFS, 12 with bipolar disorder and 16 healthy controls in this investigation.



Do I have to take part?

No, this is a research study so it is completely up to you whether or not to take part. If you agree to take part we will give you this information sheet to keep and will ask you to sign a consent form. Even if you agree to take part you can withdraw from the study at any time without giving a reason and without any effect on your current or future treatment.



What will happen to me?

Below we describe the main parts of the research study:



Consent and screening

For the screening visit we would like you to come to the Neurosciences Building at the Warneford Hospital. Here, we would ask you some questions about your general health and your mood over the last few years. This would take the form of an interview. We would also like you to complete some questionnaires about mood, anxiety and energy levels. Altogether this would take about 60-90 minutes.



If from this interview you are eligible to take part in the study and agree to do so, we will ask you to sign a consent form saying that you understand the study procedures and agree to take part in the study. You may want some time to think about participating and you can take up to two weeks to decide if you want to take part. The consent will take place at the Neurosciences Building at the Warneford Hospital and will be taken by one of the study investigators listed at the bottom of this letter.



Optional Blood Sample

On the screening or MRS visit, whichever is most convenient, we wish to take a small blood sample, about 20 ml, or the equivalent of 4 teaspoons, from you to measure markers of inflammation. Possible side effects of blood taking (venepuncture) are discomfort and bruising, dizziness and possibly fainting. Only one sample is taken during the study and any sample remaining following the planned analysis is destroyed.



MRS scanning

The MRS scanning will take place at the Oxford Centre for Functional Imaging of the Brain (FMRIB) at the John Radcliffe Hospital on a separate day and will be within about two weeks of the screening interview. There is only one scan and it will take about 60 minutes. We are hoping that the scan will give us important information about the levels of lactate in the brain in bipolar disorder and CFS relative to healthy controls.



The scanner is a large cube shape. Running through the middle of the scanner is a tube, which is open at both ends. You will enter the scanner head-first and your feet will remain outside the tube. During the scan you will hear some tapping and bleeping noises. The radiographer and researcher will be able to see you throughout the scan and we will provide you with a call button, which you can press at any time if you want to come out of the scanner. The scanner makes a loud knocking noise when it is running, and therefore participants will be provided with earplugs and protective headphones during the scan. There are no known risks of MRS scanning provided standard safety guidelines are followed carefully.



What will I have to do?

The main requirement is to attend the appointments and brain scanning when arranged. Once you have completed these visits, your participation will end in the study.



What are the possible disadvantages and risks of taking part?

MRS scanning is safe and non-invasive and does not involve any ionizing radiation (xrays). However, because it uses a large magnet to work, MRI scans are not suitable for everybody. Because of this, you will be asked pre-screening safety questions to help determine if you are able to take part. For example, if you suffer from claustrophobia, you could not be scanned. Normally, MRS scanning for research purposes would not be performed without further investigation if you have a heart pacemaker, mechanical heart valve, mechanical implant such as an aneurysm clip, hip replacement, or if you carry other pieces of metal that have accidentally entered your body.



While there is no evidence to suggest that MRI is harmful to unborn babies, as a precaution, the Department of Health advises against scanning pregnant women unless there is a clinical benefit. We do not test for pregnancy as routine so if you think you may be pregnant you should not take part in this study. As some of the scans are noisy, we would give you earplugs, head padding or headphones to make this quieter for you. It is important that these are fitted correctly as they are designed to protect your ears. In preparation for your scan and for your comfort and safety we may ask you to change into pocket-less and metal free "pajama-style" top and trousers, which are available in a range of sizes. You may keep your underwear and socks on but we would ask ladies to remove underwired bras, if you have a suitable sports type bra you may wear this instead. Please avoid any fabrics that contain metallic threads or have been silver impregnated (often marketed as anti-microbial/bacterial or anti-odour).



Metal jewelry including body piercing must also be removed. Eye shadow and mascara must also be avoided, since some types contain materials that can interact with the magnetic field. If you wish to wear eye makeup to your scan we can provide makeup removal wipes but you are advised to bring your own makeup to reapply. Lockers are provided to secure your personal belongings and clothing. Some people scanned in MRI scanners, especially 7 Tesla scanners, may experience a mild dizzy sensation as they are moved into the scanner. This is normal and the sensation starts to go away as soon as you are in the scanner.



It is important to note that we do not carry out scans for diagnostic purposes, and therefore these scans are not a substitute for a doctor’s appointment. Our scans are not routinely looked at by a doctor; rather our scans are intended for research purposes only. Occasionally a possible abnormality may be detected. In this case, we would have the scan checked by a doctor. If the doctor felt that the abnormality was medically important, you would be contacted directly and recommended to have a hospital (NHS) diagnostic scan arranged. All information about you is kept strictly confidential.



What are the benefits of taking part?



The study will not be of direct benefit to you but we hope that the information we obtain will help improve the understanding and later the treatment of CFS.



Will my taking part in the study be kept confidential?

Yes. We will follow ethical and legal practice and all information about you will be handled in confidence. The details are included in Part 2.

If the information in Part 1 has interested you and you are considering participation please read the additional information in Part 2 before making any decision.



PART TWO

What will happen if I don’t want to carry on with the study?

You can leave the study at any time, including during the scan itself. If you withdraw before the MRS scan is completed all your screening data will be destroyed.



What if there is a problem?

The University of Oxford, as Sponsor, has appropriate insurance in place in the unlikely event that you suffer any harm as a direct consequence of your participation in this study. If you wish to complain about any aspect of the way in which you have been approached or treated during the course of this study, you should contact either Dr Beata Godlewska (01865 618309, beata.godlewska@psych.ox.ac.uk) directly or you may contact the University of Oxford Clinical Trials and Research Governance (CTRG) office on 01865 572224 or you can email the head of CTRG, ctrg@admin.ox.ac.uk.



Will my taking part in the study be kept confidential?

Your data will be collected by clinical researchers and anonymized which means that it will be coded and only the study investigators will be have access to the code. All the investigators have a duty of confidentiality towards you exactly as in usual medical practice. Responsible members of the University of Oxford, or the Oxford University Hospitals NHS Trust may be given access to data for monitoring and/or audit of the study to ensure we are complying with regulations.



Anonymized study data will be stored for ten years and then disposed of securely unless we obtain further ethical committee approval to use it in a subsequent study. Your anonymized scan data might be shared with other bona fide researchers so that the maximum value of your contribution can be realized. However, no researchers outside the immediate research team will have access to any personal information about you and it will not be possible to link the scans to any particular individual.



What will happen to the results of the research study?

We hope to publish the results of the study in the scientific literature. You will not be identified in the publication. The results of the study will also be made available on our Departmental Web-site (http://www.psych.ox.ac.uk/research/psychopharmacology).



Who is organizing and funding the research?

The University Department of Psychiatry is funding the study and the research is being sponsored and organised by the University of Oxford. No payment is made to either the doctors conducting the research or the hospitals where this research is carried out if you were to decide to help with the study.



Expenses and payments

We will reimburse any expenses you incur taking part in the study (for example, travel expenses) and will also offer a payment of £50 to all participants who have the MRS scan and interviews as reimbursement for time and inconvenience.



Who has reviewed the study?

All research in the NHS is looked at by independent group of people, called a Research Ethics Committee to protect your safety, rights, well being and dignity. This study has been reviewed and given favourable opinion by the Research Ethics Committee South Central-Oxford A.



Thank you for reading this information sheet. If you have any questions please get in touch with Dr Beata Godlewska (tel: 01865-618309 or beata.godlewska@psych.ox.ac.uk)
Dr Brian Angus (brian.angus@ndm.ox.ac.uk)
Professor PJ Cowen (phil.cowen@psych.ox.ac.uk)
Dr Beata Godlewska (beata.godlewska@psych.ox.ac.uk)
Dr Ann Sharpley (ann.sharpley@psych.ox.ac.uk)
Ms Clare Williams (clare.williams@psych.ox.ac.uk)
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So what are thoughts?
Initially brain imaging at Oxford with lactate as focus seemed good. Funding by Oxford university, again good. Latest high tech, good.

Concerns -
Psychiatrists
Wasn't Brian Angus a PACE promoter
Why control with bipolar? Unless they just have interest in both conditions.
Why refer to mood symptoms when for patients with CFS it's not a chief concern.
 
Trish said:
Interesting - it looks like they are doing the same thing as in this pilot study:

Elevations of ventricular lactate levels occur in both chronic fatigue syndrome and fibromyalgia, 2017, Natelson et al
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But why's it being run by someone whose interest is in mood disorders? And with the lower patient numbers and extra control group, it looks like an attempt to generate a false negative result.
 
Cinders66 said:
Wasn't Brian Angus a PACE promoter
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Also was going to be part of MEGA. Here's what he said about PACE:
Dr Brian John Angus, Clinical Tutor in Medicine and Honorary Consultant Physician, University of Oxford, said: “This study is the largest ever done in CFS/ME and as such is critically important. The study should reassure patients that there is an evidence-based treatment that can help them to get better and there is no need to worry about harm from the treatment.”
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Edited to add: He also co-authored a PACE paper claiming CBT and GET are safe: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065570/
 
Cinders66 said:
Why control with bipolar? Unless they just have interest in both conditions.
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Personally, I'd rather that studies like this did use a depressive disorder as a control group, alongside HCs - provided that they exclude for comorbid depressive disorders in the ME/CFS group.

I'm tempted to sign up. Just need to decide whether I can schlep up to Oxford or not.
 
So what if they come up with a result that distinguishes bipolar and ME from healthy controls, but not from each other? Then what spin might they put on that, before further research could dig deeper? Being as bipolar is deemed a mental disorder.
 
Barry said:
So what if they come up with a result that distinguishes bipolar and ME from healthy controls, but not from each other? Then what spin might they put on that, before further research could dig deeper? Being as bipolar is deemed a mental disorder.
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I suppose the counter-argument is so what if they do? That would still be progress and I'd be wary of arguing that scientific research shouldn't be undertaken just because it might find an overlap with bipolar.
 
Londinium said:
I suppose the counter-argument is so what if they do? That would still be progress and I'd be wary of arguing that scientific research shouldn't be undertaken just because it might find an overlap with bipolar.
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No, I didn't make myself clear. I agree with what you say completely, the truth is what counts. With research of course, the truth unfolds over time, so along the way all you have is partial truths. I was not suggesting to run away from these partial truths, but just pondering what BPS folks might exploit if a partial truth showed a bipolar and ME similarity, without yet knowing what further truths might differentiate them.
 
Funding from Sharpe's department to a previous PACE trial promoter? Sounds bad.

This is what an anonymous spokesperson for Oxford said in the SMC's response the the JHP special issue on PACE:

A spokesperson for University of Oxford said:

“The PACE trial of Chronic Fatigue Syndrome treatments was conducted to the highest scientific standards and scrutiny. This included extensive peer review from the Medical Research Council, ethical approval from a Research Ethics Committee, independent oversight by a Trial Steering Committee and further peer review before publication in high-impact journals such as The Lancet.

“The allegation that criteria for patient improvement and recovery were changed to increase the reported benefit of some treatments is completely unfounded. As the study authors have repeatedly made clear, the criteria were changed on expert advice and with oversight committee approvals before any of the outcome data was analysed.

“Oxford University considers Professor Sharpe and his colleagues to be highly reputable scientists whose sole aim has been to improve quality of life for patients with ME/CFS. While scientific research should always be open to challenge and debate, this does not justify the unwarranted attacks on professionalism and personal integrity which the PACE trial team have been subjected to.”
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Barry said:
No, I didn't make myself clear. I agree with what you say completely, the truth is what counts. With research of course, the truth unfolds over time, so along the way all you have is partial truths. I was not suggesting to run away from these partial truths, but just pondering what BPS folks might exploit if a partial truth showed a bipolar and ME similarity, without yet knowing what further truths might differentiate them.
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You're right, there are a small coterie of BPS proponents who will always argue that any finding supports their model, by dialling up or down the B, the P or the S depending on circumstances. I suppose the flip side of that (which is why I'm a fan of using depressive disorders as an additional control group wherever possible) is that any identified cytokine/metabolic disturbance can always be counteracted by BPS proponents as 'so, you get immunological/metabolic changes in depression as well'. I might have possibly too optimistic a view, but I welcome as much research as possible unless it's out-and-out psychobabble, potentially harmful to participants, or both - because such research, in time, is in the process of showing the previous claims of the psychology lobby to be based on very dubious premises. (Even the fact that out-and-out 'false illness belief' now has to be cloaked as 'biopsychosocial factors' is a victory of sorts).
 
Londinium said:
I suppose the counter-argument is so what if they do? That would still be progress and I'd be wary of arguing that scientific research shouldn't be undertaken just because it might find an overlap with bipolar.
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The problem is that it's relatively easy for quacks to deliberately create and exploit methadological flaws in their own research to "prove" that there is no difference between patients and controls. You use fewer patients, and add more control groups - this paper is doing both. You can also add more comparisons to make, to reduce the statistical significance of results (or not, if corrections are not made). So it will likely end up (by design, rather than in reflection of reality) that ME patients are not physically different to healthy controls and/or bipolar patients.

They don't state criteria, but it will probably be Oxford, based on the symptoms they focus on:
... important symptoms such as exhaustion, poor memory and concentration and impaired sleep.
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They will make many comparisons, including an unspecified number of "brain chemicals":
The aim of this pilot study is to use this new MRS system to examine brain chemicals in people with CFS, focusing particularly on a chemical called lactate which is involved in energy production in cells and which can be measured with modern MRS systems.
Click to expand...

Blood tests are optional, but only to correlate to psychological issues:
Research studies have also noted a relationship between the immune system (how the body reacts to an infection) and the development of mood symptoms. For this reason we wish to take an optional blood sample.
Click to expand...

A lot more focus on mood. This would probably include grossly inappropriate questionnaires such as HADS, where symptoms of biomedical illness are treated as indicative of a mood disorder:
For the screening visit we would like you to come to the Neurosciences Building at the Warneford Hospital. Here, we would ask you some questions about your general health and your mood over the last few years. This would take the form of an interview. We would also like you to complete some questionnaires about mood, anxiety and energy levels. Altogether this would take about 60-90 minutes.
Click to expand...

They are trying to avoid meaningful sharing of anonymized data by writing it into the consent forms:
Your anonymized scan data might be shared with other bona fide researchers so that the maximum value of your contribution can be realized.
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Oxford University is now actively supporting and encouraging poor research practices:
The University Department of Psychiatry is funding the study and the research is being sponsored and organised by the University of Oxford.
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This study is already badly flawed, and they'll just find ways to make it worse as time goes on. It doesn't matter if they get "real" ME patients or not - they have pre-determined the results which they want, they have put methodology in place to ensure that they get those results, and then they will hide the data from the world while insisting we use their research as a basis for policy.

There is no point in engaging with this study, except to protest against the University of Oxford for funding it.
 
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Thanks @Valentijn , those are some useful points. I think you're absolutely right on not engaging with a study if it were to use Oxford criteria, and I'd also be wary of the phrase 'bona-fide researchers' w.r.t. information sharing.

As to the bit around whether the immune system 'affects mood', I'm probably less concerned. If ME/CFS were found to be due to the immune system screwing up the brain (e.g. via permeability of the blood-brain barrier) I'd actually have no problem with that - that to me *is* a biomedical illness, would fit with the current WHO classification of a neurological disorder, and IMHO is miles away from 'learned helplessness', 'false illness belief' or just plain malingering. Also, it's arguably harder to hide/manipulate the results on this experiment than it is on a subjective clinical trial.

Still, I toy with participating (subject to the selection criteria and data sharing points above) - better to have me, who meets most/all of the stricter selection criteria and who doesn't have, and has never had, any co-morbid depression in the patient group than only having those with ideopathic chronic fatigue participating.


(Entirely separately: I'm guessing this is why they are using bipolar as an extra control group - https://www.ncbi.nlm.nih.gov/pubmed/23810640)
 
adambeyoncelowe said:
Sadly, the way it's designed means they may only end up recruiting patients who already think their illness is psychological (proper ME patients will run a mile), so they're likely to prove exactly what they want to prove. I'm definitely a cynic a though...
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They'll prove what they want to prove regardless. That's the joy of badly flawed methodology - you can eliminate the impact of any unwanted variables, like the actual disease which patients have, and still get the desired outcome.
 
The defense of PACE is astounding, why take this 'weird rare disease' of ME and stake the reputations of so many researchers, institutions, and publications on its validity? Why give a quack a knighthood?

There is something here that seems out of proportion, and desperate. Pick another illness, MS, Lupus, Alzheimer's, you name it, can you imagine the same strange history and effort made principally by US and UK medical institutions with such vehemence?

It seems an elephant in the room, obvious, but problematic to bring it up without the claims of being conspiratorial, but then what sort of people call for patients to be ridiculed, to call them terrorists, and so on. They are a strange bunch, whatever their motivations.
 
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