In a small clinical trial conducted in Spain, low doses of calcitriol, an active form of vitamin D used to manage hypoparathyroidism and other diseases, produced a statistically significant increase in frataxin protein levels in patients with Friedreich’s ataxia.
Patients in the one-year study did not report any significant improvement in their symptoms, but the researchers said they “cannot exclude the possibility that higher doses and longer-term treatment may result in neurological improvement,” and urged further research.
The results of the study are: Movement disordersIn a paper titled,Calcitriol treatment is safe and increases frataxin levels in patients with Friedreich’s ataxiaThe research was funded by the Spanish Ministry of Science, Technology and Innovation and the Spain-based aid organization Federación de Ataxias de España.
Friedreich’s ataxia is a genetic disorder in which a mutation causes abnormally low levels of the protein frataxin. Recent work in experimental models suggests that treatment with calcitriol increases intracellular levels of the protein frataxin. Motivated by this finding, a team of scientists conducted a pilot study to test the effects of calcitriol on patients with Friedreich’s ataxia.
The study enrolled 20 patients, all of whom were to take calcitriol at a dose of 0.25 micrograms (mcg) per day for one year. Four of the participants had late onset of the disease, meaning they developed the disease after age 25. The supplement was generally well tolerated, with some patients reporting mild, temporary side effects, such as headaches and nausea.
Safety and tolerability highlighted
Five of the patients experienced abnormally high calcium levels while taking calcitriol and were withdrawn from the study. None of these patients experienced symptoms related to the abnormal calcium levels, and in all cases calcium levels returned to normal when calcitriol was discontinued.
“The minimal and manageable side effects and reversible hypercalcemia highlight the safety and tolerability of the drug,” the researchers wrote.
In the 15 patients who completed the one-year study, measures of neurological and motor function generally remained stable or slightly worsened after that year. Patient-reported quality-of-life measures also generally remained unchanged. Although the data did not show a clear clinical benefit of calcitriol supplements, the researchers noted that “patients’ neurological decline did not worsen with treatment,” emphasizing its safety.
Frataxin protein levels measured in platelets (cell fragments that help blood clot) showed a small but statistically significant increase after one year of taking calcitriol, from an average of 5.5 picograms per microgram to 7 micrograms per microgram.
The findings lend credence to the idea that this form of vitamin D may benefit people with Friedreich’s ataxia, but the researchers stressed that more research is needed to prove it either way. They called for future studies with more patients, longer follow-up periods, and higher doses of calcitriol.
“Future interventions could consider clinical trials with higher doses of calcitriol (e.g., 0.50 mcg daily, still the usual dose), larger patient cohorts, and/or longer treatment,” the researchers wrote. “This would allow us to see whether the increase in frataxin levels is sustained and whether it translates into reduced disease progression after 1 year of treatment.”
