Saturday, 8 November 2014

Alfacalcidol (Vitamin D analogue) trial

Are vitamin D analogues the way forward for testing the vD hypothesis? #MSBlog #MSResearch

"How do you get Pharma to sit-up and take note in the field of nutriceuticals? You medicalise it by converting the neutriceutical into a drug that allows one to patent the new compound. The patent is the mechanism that allows one to protect any investment in developing the drug and potentially allows to the company concerned to bring the drug to market and make a return on their investment."
"The study below provides proof of principle that a vitamin D analogue, alfacalcidol, works in MS-related fatigue and may have a positive impact as a disease modifying therapy. Yes, vitamin D is classified at present as a nutriceutical. In the UK you don't need a CTA (clinical trial certificate) to do a study; the MHRA states that vD is a food supplement. I am prepared to bet that they don't treat alfacalcidol as a food supplement. Nevertheless vD analogues provides a development pathway for testing the vD hypothesis in MS. There is a lot of circumstantial evidence that vD may work as a DMT in MS, but it needs to be tested in large, randomised, double-blind, placebo-controlled trials. These trials are too expensive for academics to undertake, hence the need for Pharma investment. Using a drug, instead of vD, get around this stumbling block."
"I am surprised the investigators went for MS-related fatigue as a primary outcome for this study. MS-related fatigue is multi-faceted and many of the outcome measure used to measure fatigue are poor. I am also not sure about the biology of vD and its link to MS-related fatigue. May be alfacalcidol is working via suppressing inflammation, which causes fatigue. Let's hope these results will lead to more interest in vD analogues and a phase 3 trial programme."

 


Epub: Achiron et al. Effect of Alfacalcidol on multiple sclerosis-related fatigue: A randomized, double-blind placebo-controlled study. Mult Scler. 2014 Oct 24. pii: 1352458514554053.

CONTEXT: Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS); however, there is no medication that has been approved specifically to treat MS-related fatigue.

OBJECTIVE: We aimed to evaluate the effect of vitamin D analogue, Alfacalcidol, on MS-related fatigue.

DESIGN, SETTINGS, PARTICIPANTS: This was a randomized, double-blind, parallel group, placebo-controlled trial in patients with clinically definite MS by McDonald criteria conducted in a single university-affiliated medical center in Israel. Randomly selected MSers from the Sheba MS Registry computerized database (N=600) were assessed using the self-report Fatigue Severity Scale (FSS). MSers with clinically meaningful fatigue (N=259) were further assessed for trial eligibility, and MSers with significant fatigue (N=158; 61%, 118 females, mean age 41.1 ± 9.2 years and mean disease duration of 6.2 ± 5.5 years) were included in the study and randomized to receive treatment or placebo.

INTERVENTION: Alfacalcidol (1 mcg/d, N=80) or placebo (N=78) was administered for six consecutive months.

MAIN OUTCOME MEASURE: The primary endpoint of the study was the change between Alfacalcidol and placebo-treated MSer in the Fatigue Impact Scale (FIS) score; the cut-off point for improvement was defined as 30% decrease. All analyses followed the intention-to-treat principle and were performed for all participants based on the group they were randomly allocated regardless of whether or not they dropped out.

RESULTS: Alfacalcidol decreased the mean relative FIS score as compared with placebo (-41.6% vs. -27.4%, p=0.007, respectively). This advantage was further emphasized when the modified FIS (MFIS) relative change was calculated. Quality of Life (QoL) improved in Alfacalcidol-treated MSers as compared with placebo in the RAYS psychological (p=0.033) and social (p=0.043) sub-scales. The Alfacalcidol-treated group had reduced number of relapses (p=0.006) and higher proportion of relapse-free patients (p=0.007). Reduction of relapses by Alfacalcidol became significant at 4 months of treatment, was sustained at 6 months and decayed 2 months after drug discontinuation. Alfacalcidol treatment was safe and no serious adverse events were recorded.

CONCLUSION: Alfacalcidol is a safe and effective treatment strategy to decrease fatigue and improve QoL in MSers.

6 comments:

  1. "How do you get Pharma to sit-up and take note in the field of nutriceuticals? You medicalise it by converting the neutriceutical into a drug that allows one to patent the new compound. The patent is the mechanism that allows one to protect any investment in developing the drug and potentially allows to the company concerned to bring the drug to market and make a return on their investment"

    Ain't it always the way.

    I guess I pretty much use D3 as a DMT anyway(10,000iu daily), and rarely have relapses (and no fatigue outside of a few hours on some relapses). I also take inosine (daily for 14 years), a drug that did well in phase 11 trials but I guess pharma didn't have the 'will' to take further?

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  2. 'Cos I'm curious, I thought I'd look up who has the patent. Surprise, at least one belongs to Teva. Also came across more info on who has patents for D3 in various forms here (updated to 2012 and no mention of Teva)
    http://www.vitamindwiki.com/Who+said+vitamin+D+could+not+be+patented

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  3. If alfacalcidol is proven to work as a DMT or fatigue reducer, can we conclude Vit D3 will have the same effect?

    Good for us if it's so.
    But the company will have spent all that money for nothing

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  4. Again .. it's said to inhibit TNF. Is that good or bad?
    http://www.ncbi.nlm.nih.gov/pubmed/10769429
    > D-hormone preparations (alfacalcidol, calcitriol) possess immunoregulatory effects in vitro and in vivo by inhibiting the cytokines IL-1, IL-6, TNF-alpha and particularly IL-12.

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  5. Re "I'm surprised that the investigators went for MS-related fatigue as a primary outcome"

    "Patient based evidence" is not considered acceptable or sound, but there are an awful lot of MSers out there who do claim that keeping their serum Vit D levels up above 150 nmol/L helps with their fatigue levels - regardless of whether maintaining this level comes from natural sunshine or supplementation. Not blind, not random, and no placebos in sight, but sometimes I think we need to remember that actual day to day experiences of real people can contribute something constructive to the debates. Each of us is different, and our MS affects us all in slightly different way so given that the real facts underlying so much of this stuff are not clear, if it works for someone, then let 'em go for it, especially as Vit D at such levels is not harmful.

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    Replies
    1. "if it works for someone, then let 'em go for it, especially as Vit D at such levels is not harmful"
      Hear, hear anonymous at 12:23:00 am

      Delete

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