Study Will Test Using Calcitriol to Boost Frataxin
A clinical trial will assess whether supplementation with calcitriol, the active form of vitamin D, can boost frataxin production in people with Friedreich’s ataxia (FA).
The Biochemistry of Oxidative Stress Group (BOSG) at the Biomedical Research Institute of Lleida (IRBLleida) and the University of Lleida, in Spain, announced their proposed trial in a press release.
Low levels of the frataxin protein underly the symptoms of FA. The deficiency leads to the death of nerve cells in the brain and spinal cord, and also the nerves that control muscle movements in the limbs.
Earlier this year, BOSG researchers demonstrated that calcitriol use is associated with increased frataxin production in FA cell models, providing a molecular basis to test the therapy in clinical trials.
The new trial (NCT04801303) is a 12-month study to assess the use of calcitriol (0.25 micrograms a day for a year) in patients with FA. The study, which will start in September to ensure all participants are vaccinated against COVID-19, will take place at the Hospital Santa Caterina, in Salt, Catalonia. More information about enrollment is available here.
Investigators seek up to 20 participants, who will make six clinical visits during their year of treatment.
Participants must have a genetic FA diagnosis with either two pathological GAA repeats in their FXN gene, or such a repeat with a point mutation in FXN, and be 16 to 65 years old.
The trial’s main goals are to measure changes in participants’ neurological function, quality of life, and frataxin production.
Neurological function will be measured with several standard scales, including the Scale for the Assessment and Rating of Ataxia, the Nine-Hole Peg Test, and the Eight Meters Walking Test. Quality of life will be assessed using the SF36 questionnaire and frataxin production will be measured in blood drawn from patients.
Secondary trial goals include the evaluation of the safety of calcitriol supplementation and the risk of reaching dangerously high calcium levels, a condition called hypercalcemia.
Joaquim Ros, PhD, and Jordi Tamarit, PhD, from the University of Lleida, will monitor biochemical parameters of individuals during the trial. They received international funding in 2017 for the creation of a new FA mouse model developed by introducing a point mutation — the change of a single DNA nucleotide — in the frataxin gene, leading to an unstable frataxin protein.
The trial is supported through a research grant from the Spanish Federation of Ataxias.
According to the trial’s webpage, “results of the present study, if positive, would lead to the organization of trials at a larger scale, and they would allow the use of an effective treatment for patients with FA.”