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The Synergy Trial: Phase 2 results out

Discussion in 'Latest ME/CFS Research' started by John Mac, Sep 13, 2017.

  1. John Mac

    John Mac Senior Member

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    http://www.kpaxpharmaceuticals.com/the-synergy-trial

    A follow up study to the phase 1 study discussed here:

    http://forums.phoenixrising.me/inde...henidate-ritalin-trial-results-are-out.37363/
     
  2. A.B.

    A.B. Senior Member

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    Thanks. The description of results is sadly insufficiently detailed to understand whether this treatment is useful.

    This sounds like results were generally not statistically significantly different compared to the control group.

    Okay, but how well did the control group do? If they had similar results then this means nothing.

    Generally poor results is what I would expect. Conceptually ME/CFS seems to be a state of dysregulation, hypersensitivity and controlled shutdown and a stimulant isn't going to do much good for any of these. There was some chance that this combination could work to address energy production deficits but doesn't look like it's working well.
     
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  3. Groggy Doggy

    Groggy Doggy Guest

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    I wonder, were the study results gained strictly via a patient's self report? Were the study participants promised a discount to purchase the KPAX nutrient product?

    Looks like KPAX wants to start phase 3 trials.

    http://www.kpaxpharmaceuticals.com/partnering-opportunities
     
    Valentijn likes this.
  4. A.B.

    A.B. Senior Member

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    I'm fine with that. Maybe it's useful for a subgroup and they think they can make it work for that purpose.
     
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  5. Groggy Doggy

    Groggy Doggy Guest

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    I would prefer the study participants undergo some kind of before and after testing with for example CPET. I don't know how reliable self reporting is, especially as you pointed out that we need to see what the control group results are.
     
  6. trishrhymes

    trishrhymes Senior Member

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    At the very least I think they should have them wearing actometers throughout the trial and for many months afterwards.
     
  7. Groggy Doggy

    Groggy Doggy Guest

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    It might be cheaper, and simpler for a ME peep to simply purchase an inexpensive bottle of a few of the listed ingredients (NAC, ALCAR, etc) to see if any improvement is gained (by taking just one ingredient at a time for a few weeks). I am not a proponent of taking a multi-supplement product without understanding which ingredients are helpful/do nothing/hurtful. If a stimulant is desired then I suggest possibly working with an MD to get Rx for Phentermine.

    Phase 3 FDA trials are very expensive. Seems like a lot of money that could be better spent on funding ME scientific research (ex: OMF).
     
    Last edited: Sep 13, 2017
    Persimmon likes this.
  8. Murph

    Murph :)

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    The IACFSME conference last year included a report from Lucinda Bateman on this trial.

    I looked at the data at the time. The patients got a lot better but so did the controls! Certainly a frustrating one.

    Here's the rundown from the conference:

    The Synergy Trial for CFS – A Phase 2 Study of Low-Dose Methylphenidate plus Mitochondrial Support in Patients with Chronic Fatigue Syndrome


    Lucinda Bateman, MD, Nancy Klimas, MD, Jose Montoya, MD, Susan Levine, MD, Jon D. Kaiser, MD


    Background


    CNS stimulants have been utilized to treat CFS symptoms though their benefits are often limited and their tolerability is uncertain. Evidence of mitochondrial dysfunction in CFS patients has also been identified in several publications. Micronutrient support has been shown to improve mitochondrial function. One open-label trial in CFS patients has been published showing a significant benefit to combining these two treatment modalities.


    Objectives


    This Phase 2 multicenter, double-blinded, placebo-controlled trial (n=128) was performed at four US research clinics to examine the clinical effects and safety profile of combining low-dose methylphenidate plus mitochondrial micronutrient support in patients with CFS.


    Methods


    128 CFS patients (1994 Fukuda criteria) were randomized in double-blinded fashion to two parallel arms: a double treatment group (methylphenidate + mitochondrial support) and a double placebo group to investigate the potential synergistic effect of this combination. Fatigue and concentration disturbance symptoms were measured at baseline, 4 weeks, and 12 weeks using two clinically validated tools: Checklist Individual Strength (CIS) and Visual Analog Scale (VAS). The primary objective of the study was to measure the treatment’s safety as well as its efficacy utilizing the change in CIS total score.


    Results


    At twelve weeks there was a change in the mean CIS total score of -16.9 in the treatment group and -13.8 for the placebo group when compared to baseline (P = 0.36). In the PP population, there was a change in the mean CIS total score of -20.9 in the treatment group and -12.6 for the placebo groups at Day 84 (P = 0.19). The change in the mean VAS score for fatigue from baseline was -18.2 in the treatment group and -11.1 in the placebo group (P = 0.19). Adverse events were not significantly different between the two groups.


    Conclusion


    Treatment with low-dose methylphenidate plus mitochondrial micronutrient support in CFS patients was well tolerated during this trial. Using a validated patient reported outcome measurement tool, overall CFS symptoms decreased in a majority of the treatment subjects. Though statistical significance was not achieved in this Phase 2 trial, all analyses revealed an advantage to the treatment group. Further investigation is warranted.


    - Lucinda Bateman, MD, Medical Director Bateman Horne Center1002 E. South Temple, Suite 408
    Salt Lake City, Utah 84102


    - This trial was sponsored by K-PAX Pharmaceuticals, Mill Valley, CA - No conflicts of interest.
     
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  9. dreampop

    dreampop Senior Member

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    This trial was sponsored by K-PAX Pharmaceuticals, Mill Valley, CA - No conflicts of interest.

    Uh?

    No statistical significance? So, does anyone know what's in the mito micronutrient.

    This is one I'm a little iffy on. Stimulants really seemed to worsen some of my symptoms, though I haven't taken Ritalin. I have heard some people get worse fatigue on them after a few hours - although I guess the mito supplement could prevent that. But that's all in addition to it's numerous side effects.

    But mostly I'm wondering if they are noticing Ritalin is a decent treatment for orthostatic intolerance/pots of which many with ME/CFS have.
     
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  10. Snow Leopard

    Snow Leopard Hibernating

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    The results aren't "out" unless they're published...
     
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  11. madone

    madone

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  12. debored13

    debored13 Senior Member

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    wow this seems like one of the dumbest medicines I've seen

    how the fuck does a stimulant like methylphenidate "treat" a hypometabolic state? Stimulants would just stress the metabolism more, which is I guess what the nutrients in it are there for, but this is in no way a novel idea, even if they give it a novel name
     
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  13. nanonug

    nanonug Senior Member

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    I'm surprised CoQ10 wasn't included as a mitochondrial support nutrient. And based on what we now know, anything without dichloroacetate will probably won't help a great deal.
     
  14. ljimbo423

    ljimbo423 Senior Member

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    I tried methylphenidate (Ritalin) for a year or so. It helped for a few weeks then did almost nothing for me, even though I was taking 20-30 supplements a day with it.

    As you said, it doesn't address the cause of the mitochondrial dysfunction. Rather it puts more stress on them, like whipping an exhausted horse. You might get more energy out of the horse short term, eventually it will collapse.

    High dose coq10 is helping me a lot with increased energy and reduced PEM, at 575mg a day. My feeling is the mito. need to be supported naturally, not forced to overwork.

    Jim
     
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  15. debored13

    debored13 Senior Member

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    what do you mean anything without dca won't help?
     
  16. debored13

    debored13 Senior Member

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    I had methylphenidate for adhd before I ever got lyme. It worked well and wasn't overstimulating. after I got lyme and then cfs (metabolic dysfunction) I had horrible reactions to it. I have like 6 months of ritalin just sitting around
     
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  17. nanonug

    nanonug Senior Member

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    If PDH impairment is indeed a characteristic of SEID as shown by Fluge et al, then not addressing it is not going to help a great deal. Outside of some weird research compounds, DCA is only thing (to my knowledge) that specifically addresses the PDH impairment.
     
  18. debored13

    debored13 Senior Member

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    It probably is a characteristic, but I doubt it's the primary culprit. More likely that it's part of a larger problem. DCA also isn't the only thing that would address PDH impairment, and it's proven to be somewhat toxic.

    It's interesting to note the similarities and differences between cfs and pyruvate dehydrogenase complex deficiency. In both, there's too much lactic acid, and fatigue, but with the latter, its a lot more severe, not to undermine cfs. But in the latter people die often very young from the lactic acidosis.

    Thiamine, especially high dose, may serve a similar purpose as DCA. Lipoic acid, biotin also.
     
  19. debored13

    debored13 Senior Member

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    I think that Ron Davis and Naviaux are both working with the knowledge that PDH impairment has been shown to be a problem, but I think they're working on illuminating the larger context. Hope it happens fast.
     
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  20. debored13

    debored13 Senior Member

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    what i'm saying is really that I don't think anybody should be under the impression that DCA is the only treatment out there. There are a bunch of different components to CFS. So far I haven't really found any cures, but only tiny, brief alleviation of symptoms. However, some people find relief with a variety of drugs or supplements. It doesn't make sense to focus only on this one, although the problem of reductive stress/PDH inhibition is an important one
     

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