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Disease Mechanisms and Clonidine Treatment in Adolescent Chronic Fatigue Syndrome

Discussion in 'Latest ME/CFS Research' started by A.B., Feb 5, 2014.

  1. A.B.

    A.B. Senior Member

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    Disease Mechanisms and Clonidine Treatment in Adolescent Chronic Fatigue Syndrome

    http://archpedi.jamanetwork.com/article.aspx?articleid=1827799
     
  2. anciendaze

    anciendaze Senior Member

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    To reiterate: many patients, particularly adolescents, show orthostatic hypotension. Clonidine is commonly used to treat hypertension, high blood pressure. This should make clonidine contraindicated. This is also a major problem with CFS patients tolerating common antidepressants.

    My bolding. If EBV is not a common microorganism, what is? (In reference to this report.)
     
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  3. CBS

    CBS Senior Member

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    The principle investigator for this study is Vegard Bruun Wyller. He was a key player in de-funding the Rituximab phase III study in Norway, likely because he felt that it would draw attention and money away from his pet hypothesis, that CFS is a minor neurological signaling disorder. Two items are of note with this study; 1) it was a colossal failure - chlonidine actually decrease activity in CFS patients (no small feat considering how hard it is for us to be active) and 2) Peter Rowe was a collaborator and turned out to be just as wrong as Wyller.

    They should however receive some credit for actually publishing a study that so definitively disproved their presumptions about CFS. Looks like it's back to the drawing board for these two. Now, if they'll just stay out of the way of Fluge and Mella.


    Disease Mechanisms and Clonidine Treatment in Adolescent Chronic Fatigue SyndromeA Combined Cross-sectional and Randomized Clinical Trial ONLINE FIRST
    Dag Sulheim, MD1,2; Even Fagermoen, MD3,4; Anette Winger, RN, MA3,5; Anders Mikal Andersen, BSc6; Kristin Godang, BSc7; Fredrik Müller, MD, PhD8; Peter C. Rowe, MD, PhD9; J. Philip Saul, MD10; Eva Skovlund, PhD11,12; Merete Glenne Øie, PhD13,14; Vegard Bruun Wyller, MD, PhD1,15,16

    [-] Author Affiliations 1Department of Paediatrics, Oslo University Hospital, Oslo, Norway
    2Department of Paediatrics, Lillehammer County Hospital, Lillehammer, Norway
    3Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway
    4Department of Anesthesiology and Critical Care, Oslo University Hospital, Oslo, Norway
    5Institute of Nursing Sciences, Oslo and Akershus University College of Applied Sciences, Oslo, Norway
    6Department of Pharmacology, Oslo University Hospital, Oslo, Norway
    7Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, Oslo, Norway
    8Department of Microbiology, Oslo University Hospital, Oslo, Norway
    9Department of Pediatrics, the Johns Hopkins University School of Medicine, Baltimore, Maryland
    10Department of Pediatrics, Medical University of South Carolina, Charleston
    11School of Pharmacy, University of Oslo, Oslo, Norway
    12Norwegian Institute of Public Health, Oslo, Norway
    13Department of Psychology, University of Oslo, Oslo, Norway
    14Innlandet Hospital Trust, Lillehammer, Norway
    15Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo, Oslo, Norway
    16Department of Paediatrics, Akershus University Hospital, Nordbyhagen, Norway
     
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  4. A.B.

    A.B. Senior Member

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    When I read what Clonidine was used for, I thought that it would make patients worse, and so it did. It's not unsurprising either, at least for us patients, but doctors often seem to have views on CFS that are unrelated to reality. To their credit, they admitted that Clonidine made patients worse, so they do seem to be genuinely interested in reality.

    If only they understood that CFS isn't a motivational, mood, or belief problem, and that reduced activity is a survival strategy enforced by the body struggling with a serious underlying problem.
     
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  5. CBS

    CBS Senior Member

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    "He (Wyller) said the study (Fluge and Mella) does not necessarily indicate that the disease is due to autoimmune mechanisms.- This is only one of several possible hypotheses. For example, other data have shown that the autonomic nervous system plays a role. Phenomena associated with central nervous system may provide just such immunological changes that we see in ME patients . Also hormonal and psychological factors influence the clinical picture , which is complex and multifactorial , says Bruun Wyller ."

    My bold and my underline.
     
  6. CBS

    CBS Senior Member

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    Not so fast:

    "Wyller from child clinic at the hospital understand the disease from a stress response hypothesis, and recommend treatment with cognitive behavioral therapy and graded exercise. The criteria for diagnosis is wide .Wyller believe that anyone who is tired long enough and have nothing else , they have this. Wyller recommended in children and adolescents taking the Lightning Process course ( LP ) in Active process "because many items are well aligned with what we otherwise know of the condition ."LP instructor Live Landmark in Active Process writes on his blog : "All participants must be convinced that they know that we teach in a way where they can be turn or affect a condition that can be caused or maintained by stress. »"
     
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  7. A.B.

    A.B. Senior Member

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    Point taken. It makes sense that systematic incompetence would stem from incorrect assumptions given undue credit.
     
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  8. Dolphin

    Dolphin Senior Member

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  9. kaffiend

    kaffiend Senior Member

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    California
    I have taken Tenex (guanfacine) for several years. It's a pre-synaptic alpha2A agonist similar to clonidine but it's more centrally acting. It has worked quite well for the "wired" part of the the wired/tired feeling. There is also a lot of research showing how guanfacine can improve working memory circuits in the brain. Shire has actually made an extended release version and it's now FDA approved as a non-stimulant treatment for ADHD.

    I also recall the Lights' research showing up regulation of alpha2A receptors after exercise.
     
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  10. Soundthealarm21

    Soundthealarm21 Senior Member

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    I take clonidine daily and it is a very helpful medication (I use it solely for sleep, nothing else). When i'm going through a bad detox it is the one sure thing that will knock me out.


    Edit: I have higher blood pressure (Not high, but on the higher side of normal)
     
  11. LaPerla

    LaPerla

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    Norwegian study does not support "sustained arousal hypothesis"?

    CONCLUSIONS
    ABSTRACT | METHODS | RESULTS | DISCUSSION | CONCLUSIONS | ARTICLE INFORMATION | REFERENCES

    Adolescent CFS is associated with enhanced sympathetic nervous activity, attenuated hypothalamus-pituitary-adrenal axis, low-grade systemic inflammation, slight cognitive impairment, and large activity reduction, but not with common microorganisms. Sympathetic enhancement might cause inflammation, but neither sympathetic enhancement nor inflammation appears to contribute to physical disability or fatigue. Low-dose clonidine is not a clinically useful therapy in adolescent CFS; rather, it appears that the autonomic and inflammatory processes that clonidine blocks may have beneficial effects.

    Link to the study:

    http://bit.ly/LsC5Wy
     
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  12. Bob

    Bob

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    England (south coast)
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  13. Sushi

    Sushi Senior Member Albuquerque

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    @LaPerla @Bob

    Note: These two threads are now merged
     
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  14. LaPerla

    LaPerla

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    Thanks!
    I'm sorry, I did not notice the first discussion about the paper :)
     
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  15. Dolphin

    Dolphin Senior Member

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    I just read this paper. I thought the authors were fair in their reporting. It was good to have the e-supplement with all the extra info that didn't fit in the main paper (it would be good if more investigators did this).

    In terms of the number of steps per day, the healthy controls had an average of 10 302.

    It was more a case of the placebo group increasing their steps than the active group decreasing.

    Clonidine:
    Baseline: 4670
    8 weeks (end of trial): 4631
    30 weeks (they were long off the drug by this time): 4682

    Placebo group:

    Baseline: 4564
    8 weeks (end of trial): 5212
    30 weeks (they were long off the drug by this time): 4652

    Though they did find:

     
    Last edited: Feb 19, 2014
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  16. Dolphin

    Dolphin Senior Member

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    There was a good adherence rate (they counted the tablets left at the end):
     
  17. Dolphin

    Dolphin Senior Member

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  18. Dolphin

    Dolphin Senior Member

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  19. Dolphin

    Dolphin Senior Member

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  20. CBS

    CBS Senior Member

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    Hi Dolphin,

    Thanks for this series of posts. I too have found Dr. Wyller to be professional in how he presents his research. Nearly three (?) years ago we had an extended exchange during which he provided me a copy of the entire NorCal protocol. During the exchange, I raised a number of questions about alternative explanations if the NorCal project failed to support his hypothesis (which really can be boiled down to viewing CFS as relatively minor signaling disorder that involves the HPA axis).

    He does use a fairly relaxed set of criteria for patient selection and I doubt that this works in his favor (even though I disagree with his hypothesis). On the other side of this issue, I personally feel that the criteria he uses reflects his view of CFS as a less serious condition. That said, even using his less selective criteria, he does have some very interesting findings in two previous study which included significantly lower levels of ADH in patients compared to controls.


    I have taken a very close look at this earlier study and I would argue that due to the skewed nature of his findings within the patient group, he likely has two sub-groups, a group that many on this forum would describe as having ME and another group which may be defined "non-ME". If the subject group in this previous study is composed of two subgroups and only one of them contributed all of the differences in ADH levels, the "ME" patient group would have to had dramatically lower ADH levels in order for this difference to have remained evident (at a p <= 0.001 level!), even after having been diluted by the non-"ME" patients.

    At this point, the question for me is, "what does Wyller now do with the findings of a very large and expensive study that have nor supported his hypothesis?" I find his suggestion that some combination of deconditioning and/or cohort contamination with depression less than encouraging.

    Shane
     

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