Home orthostatic training in CFS-- a randomized, placebo-controlled feasibility study

[Dolphin]

Full free text at: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2362.2009.02225.x/full

Home orthostatic training in chronic fatigue syndrome--a randomized, placebo-controlled feasibility study

Eur J Clin Invest. 2010 Jan;40(1):18-24. Epub 2009 Nov 12.

Sutcliffe K, Gray J, Tan MP, Pairman J, Wilton K, Parry SW, Newton JL.

UK NIHR Biomedical Research Centre in Ageing - Cardiovascular Theme, Newcastle, UK.

Abstract

BACKGROUND: Orthostatic (Tilt)-training is an effective treatment for neurally mediated hypotension (NMH). NMH is a frequent finding in chronic fatigue syndrome (CFS). We evaluated home orthostatic training (HOT) in CFS in a randomized placebo-controlled feasibility study.

METHODS: Thirty-eight patients with CFS (Fukuda Criteria) were randomly allocated to daily tilt training (n = 19) or sham training (n = 19) for 6 months. Haemodynamic responses to standing were performed in all subjects using continuous technology (Taskforce) at enrolment, week 1, 4 and 24. Symptom response and compliance were assessed using diaries.

RESULTS: Two patients (one from each arm) withdrew from the study. Fourteen patients in each group complied completely or partially, and patients found the training manageable and achievable. Compared to the sham group, blood pressure while standing dropped to 8.0 mmHg less in the HOT group at 4 weeks (95% CI: 1.0 to 15.0, P = 0.03). At 4 weeks, the HOT group had higher total peripheral resistance compared to the sham group; mean difference 70.2, 95% CI: -371.4 to 511.8. Changes were maintained at 6 months. There was no significant difference in fatigue between groups at 4 weeks (mean difference 1.4, 95% CI: -13.5 to 16.2), but there was a trend towards improvement in fatigue at 6 months. Compliers had lower fatigue compared to non-compliers.

CONCLUSIONS: A placebo-controlled study of HOT in CFS is feasible. HOT is well tolerated and generally complied with. A likely physiological rationale for HOT in CFS is related to reductions in orthostatic intolerance. An adequately powered study including strategies to enhance compliance is warranted.

PMID: 19912315 [PubMed - indexed for MEDLINE]

 

[Snow Leopard]

I'd like to see the results on how long the active treatment group subjects were actually standing for.

Overall, the results are very unimpressive.
The results on fatigue were non significant and although there was a drop in SBP, the result (12.5-12.6) was barely lower than the placebo baseline (13.0). I suggest there is significant variability in these measures, resulting in a type 1 error.


While 'placebo controlled' may be argued, whether it was well controlled is a matter for debate.

HOT therapy.  Subjects within HOT arm were asked to stand with their upper back against a wall and their heels approximately 15 centimetres (cm) from the wall with a cushioned “drop zone”. They were asked to maintain this position without movement for up to 40 min or until they experienced symptoms.

Sham training.  Subjects were asked to stand against a wall as described above for only 10 min. They were also taught to perform gentle flexion and extension exercises with their calf muscles while standing against the wall, to enhance believability, counter venous pooling and prevent any possible orthostatic training effect.

Any communication between the subjects would easily reveal the difference. It is possible that any such respondents might reply "I don't know" to the question of sham vs active, to hide such discussion.

 

[Dolphin]

I'd like to see the results on how long the active treatment group subjects were actually standing for.

Overall, the results are very unimpressive.
The results on fatigue were non significant and although there was a drop in SBP, the result (12.5-12.6) was barely lower than the placebo baseline (13.0). I suggest there is significant variability in these measures, resulting in a type 1 error.

Or simply if your sham treatment actually has a negative effect on people, it puts the whole study in doubt. Like you I don't like what they did here at all. And in the abstract, one isn't given the numbers, only the difference at the end so people can't see it.

Deep in the piece, they do mention the problem but the way they talk up the results means it doesn't really count

Furthermore, were the statistical differences that we found related to changes in the placebo group rather than to improvements in the active HOT group?

I admit I got lost when talking about TPRI. But it seems unclear to me how the result for HOT can be said to be good on this measure:

TPRI:
Placebo:
Before: 2918.7 (SD: 856.1)
After: 2723.1 (938.9)

HOT:
Before: 2937.7 (952.4)
After: 2810.5 (888.9)

Group difference: 51.1 (-399.0 to 501.2), P=0.8

Impedance cardiography
There was little difference in the cardiac index between the two
groups at week 4 or 6 months. However, there is a suggestion
that patients in the HOT group had a higher total peripheral
resistance (TPRI) than patients in the sham group (Table 1).
This improvement was sustained to 6 months with TPRI 229.7
units higher in the tilt training group compared to the sham
group (95% CI: -258.5 to 718.0, P = 0.3).

If a high TPRI is good, they were both better at the start than after treatment, so the HOT treatment just made people less worse.

If a low TPRI is good, then the placebo did better than HOT.

 

[Dolphin]

Where are the results at 6 months?

I don't like that they only give us little bits of the results at 6 months.

 

[Dolphin]

Drop-outs/people made worse

I don't like how they deal with the issue of drop-outs. Also, people being made worse should be seen as at least as important as improverers but they don't stress that.

 

[Sasha]

I must read this study properly - I'm interested in this kind of training because drug and other treatments for OI aren't much fun. I'd like it to succeed - I'd be thrilled if I could stay upright and sit in a chair rather than having to sit with my feet up or lie down all the time, which is what keeps me housebound. I know Prof Julia Newton had been doing something on this at Newcastle University.

 

[Cort]

What is HOT?

 

[Snow Leopard]

What is HOT?

From the title of the article "Home orthostatic training". I quoted the "method" in my previous post.

 

[pictureofhealth]

'Strategies to enhance compliance' always sounds worrying to me. Surely if the treatment was so effective, there would be no need. Open heart surgery is pretty risky and extraordinarily painful, but you never hear of surgeons having to adopt 'strategies to enhance (patient) compliance'.

In general I think Julia Newton and her team appear to have done a number of excellent research studies, but if patients are not complying with a suggestion, there must be a VERY good reason, for eg, they must be having physical difficulties with the treatment or other aspects, that are not being adequately addressed ...

I still think there are some aspects of the illness that Newton and team are missing though. For eg, this is also an immune system and metabolic disorder - so perhaps a patient is feeling fluey and dizzy and in pain and unable to comply - I don't see how improving or restoring ANS function on its own is going to get rid of a viral infection in the lymphatic system for eg.

Edited having re read some of above! aargh.

 

[Snow Leopard]

Surely if the treatment was so effective, there would be no need. Open heart surgery is pretty risky and extraordinarily painful, but you never hear of surgeons having to adopt 'strategies to enhance (patient) compliance'.

Actually, you do hear of such things, as many people find the idea of open heart surgery quite frightening and are occasionally willing to risk the alternative!

 

[Angela Kennedy]

Actually, you do hear of such things, as many people find the idea of open heart surgery quite frightening and are occasionally willing to risk the alternative!

I have to ask - are there actual papers showing non-compliance in open heart surgery? If so, how is 'compliance' achieved?
The issue of 'compliance' in health care is often discussed, in terms of recalcitrant patients - but only in some areas (ME/CFS I think being one major one, and other 'mental health' interventions.)

 

[Snow Leopard]

I admit to not having read papers on the subject (which doesn't really interest me), but the topic of compliance is certainly discussed:

http://www.ncbi.nlm.nih.gov/pubmed/11216275
http://bjp.rcpsych.org/cgi/content/abstract/163/3/285
http://www.ncbi.nlm.nih.gov/pubmed/3114447
etc

The nature of such compliance might be a littler different to what you were referring to though.

 

[pictureofhealth]

As least with modern medical techniques nowadays there are some alternative options for heart patients to actual heart surgery (inserting stent via femoral artery for eg) - although potentially less effective depending on the degree of disease progression of the patient - but at least they won't be threatened with sectioning for saying 'no' (altho the Consultant might secretly think they're nuts of course)!

Usually the very real possibility of dying from severe heart disease and leaving one's family behind is enough to 'coerce' patients with severe heart disease into accepting potentially life saving/enhancing surgery and ensure compliance.

 

[Dolphin]

Compliance is a complicated issue.
I'm no expert but lots and lots of people aren't completely compliant with drug regimes i.e. take them every day.
But the standard analysis is "intention to treat" where one uses everyone who agreed to take part or maybe everyone who started. Sub-analyses can be useful but don't tell one everything.

The heart surgery comparison isn't perfect as it's very scary and you either do it or you don't.
In this, people stopped. It could be as was suggested, it wasn't working or could actually have been making somebody worse. Or expecting somebody with ME/CFS to use their time and energy to do 40 minutes standing is a big commitment that many may not be in a position to do. It's maybe a bit like people with ME/CFS not being compliant with an exercise program - pushing everyone to be compliant is risky.

 

[Angela Kennedy]

I'm looking at the issue of 'compliance' from a sociological, conflict theoretical lens: how 'compliance' is demanded even when treatments are dodgy and no patient should rationally 'comply'. There is massive conflict in many doctor-patient relationships which has been constructed as wise doctors versus recalcitrant patients, when this is an extremely unsafe interpretation, and quite significant when thinking about 'patient empowerment' versus patient/doctor power relations etc. Obviously GET, CBT and psychogenic dismissal is a very interesting example of these problems.

 

[urbantravels]

Compliance is a big issue in HIV drug regimens; the problem has improved since the early days, when the drug "cocktails" were insanely complicated and you had to take multiple pills at different times of day, some on empty stomach, some with food, etc. They've helped that problem by developing more streamlined regimens, but there are still patients who don't take their meds properly, even when the alternative is a decline into AIDS and likely death. Side effects are still a big issue.

It seems reasonable to question closely the reasons why patients drop out of a study or don't "comply" with a treatment regimen and be willing to re-examine your assumptions about the benefits of your proposed treatment.

 

[Dolphin]

Currently, there are few biological based treatments for CFS, and we believe that this study provides first insights into a novel treatment that could easily and cheaply be integrated into existing clinical services and addresses the physiological abnormalities found frequently in those with CFS.

I think this is their driver (which may make them biased).

Money is tightly controlled in the NHS, especially when dealing with ME/CFS patients.

It can be good to look for easy and cheap treatments. However, life may not be as simple. It reminds me of graded exercise (walking, etc). - it's such a seductive idea - so many doctors around the world love to recommend it. It's cheap and "easy" (to recommend) also. Doesn't mean that's what patients should be told to do.

 

[pictureofhealth]

I'm looking at the issue of 'compliance' from a sociological, conflict theoretical lens: how 'compliance' is demanded even when treatments are dodgy and no patient should rationally 'comply'. There is massive conflict in many doctor-patient relationships which has been constructed as wise doctors versus recalcitrant patients, when this is an extremely unsafe interpretation, and quite significant when thinking about 'patient empowerment' versus patient/doctor power relations etc. Obviously GET, CBT and psychogenic dismissal is a very interesting example of these problems.

Agree with all posts above - especially this one!

 

[Desdinova]

Hum seems to be a lot of Study’s being done on The Syndromes (IBS, CFS, FM) involving Placebo's. Personally if these are people suffering from any of the three listed ones sheer desire to get well can provide some perceived but unsustainable short term improvement. But when one is truly suffering from something that is physical in origin it will in most cases become evident that one is in fact still not well.

Just a few days ago I heard on one of the news channels about the IBS placebo study. That study really alarmed me as someone who suffered from IBS for years. And for the potential implications for CFS/ME and FM http://pagingdrgupta.blogs.cnn.com/..._campaign=Feed2Fcnn_gupta+3A+Paging+Dr.+Gupta)

 

[IamME]

It seems reasonable to question closely the reasons why patients drop out of a study or don't "comply" with a treatment regimen and be willing to re-examine your assumptions about the benefits of your proposed treatment.

That's not what they're doing though, they're thinking about ways to *improve* compliance, not consider whether being non-complient might actually be a good idea for some or that there might be a biomedical reason for noncompliance. They're convinced the treatment is or virtually is 100% safe and 100% appropriate despite the appalling shortcomings of this study -- excluding people with neurological or cardiovascular illness(!) or people who couldn't stand 40 minutes(!). yet claiming it's appropriate "for all"!

The biggest question they need to ask themselves is why did graded standing seem a good idea for a people for whom graded exercise is the worst possible treatment, who may have a disease (not deconditioning) perpetuated heart/vascular abnormality as per Cheney, Baraniuk, Lerner, Spence et al, and how does this help them distinguish "CFS" from deconditioning?

They then have the temerity to try to argue that doing this "successful" behavioural graded activity somehow proves the case for pharmacological treatment. That would be like Peter White turning round and saying CBT/GET is ok as it points towards a need for mito treatment (compare with the psychs' low cortisol research findings which has lead to nothing except more psychobabble). Why not just do the study on midodrine to start with?! Or are we to believe physiotherapists are needed to prescribe it. Maybe midodrine is Newton's equivalent of antidepressants in lieu of CBT. (IIRC midodrine may not be appropriate for severely affected cases with diastolic heart dysfunction either.)

This is treating us in a similar way to the morbidly obese non-diseased or some other lifestyle health choice in that everyone is pressurised to "go on a diet" until just maybe someone comes up with a fat loss pill or miracle margarine for the "stubborn" cases. Nothing to do with having an intractable pathogenic disease process. It encourages and reinforces views of us as weak, addictive/avoidant people "who've let ourselves go" and who probably don't have a serious disease process but (cue psychobabble) probably did have something years ago that went away leaving only a self-perpetuated "state" and too much stupidity or comfort(!) to realise it.

Maybe just disregard it as non-CCD CFS as opposed to CCD ME/CFS research? This isn't "CFS" as you'd recognise it.

I really don't know how people can compare this to compliance in HIV treatment or heart surgery. For a start these pathologies well understood and diagnosis is impeccable, the benefits far outweigh the risks and adverse effects well understood and prepared for, unlike with this. The dangers of increasing energy output and stressing the ME heart are far more than just "side effects", they're the MAIN DEAL.