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."
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.