Evaluation of the Effects of Calcitriol's in the Neurological Symptoms of Friedreich's Ataxia Patients
Condition: Friedreich Ataxia
MeSH terms: Ataxia; Cerebellar Ataxia; Friedreich Ataxia
Study type: Interventional
Phase: Phase 4

Summary: 
      Friedreich's Ataxia (FA) is an autosomal recessive disease the mutation of which leads to a
      deficiency of a protein called frataxin, which is responsible for the symptoms of the
      disease. It is assumed that inducing an increase in the production of frataxin could reverse
      part of the disease's symptoms.

      Several treatments with drugs that raise frataxin levels have been tested, but they have
      either have not given the expected result or have induced intolerable side effects. The
      IRBLleida (Institut de Recerca Biomèdica de Lleida Fundació Dr. Pifarré) team has shown that
      calcitriol can increase the production of frataxin up to 2.5 to 3 times, a higher proportion
      than any of the drugs previously tested. For that reason, the next step in our research would
      be to check the effects of this drug (Calcitriol 0.25mcg/24h for a year) in patients with FA.
      On the other hand, calcitriol, the active form of vitamin D, is a drug with a very low rate
      of adverse effects that has been used for decades. Therefore, it is a drug with a very well
      established tolerability. The 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.
    

Detailed description: 
      Friedreich's Ataxia (FA) is a recessive hereditary disease due to GAA
      (Guanine-Adenosine-Adenosine) triplet repeats in the FXN (Frataxin) gene. This gene codifies
      for the frataxin protein, the lack of which produces the neurological and cardiac symptoms.

      The exact mechanisms why the lack of frataxin produces the disease aren't well understood,
      but it is known that frataxin is located in the mitochondria. Calcitriol synthesis, a
      mitochondrial process, could be impaired in FA due the reduction of CYP27B1 (Cytochrome P450,
      family 27, subfamily B, member 1) and Fdx1.

      Because of some studies have shown that Calcitriol (the active form of D Vitamin) could raise
      the frataxin levels, it could have a beneficial effect in patients with FA.

      Description of the trial: to assess the effect of Calcitriol 0.25mcg/24h for a year in the
      neurological function of FA patients.

      Main objective of the trial: to evaluate the effects of Calcitriol in the neurological
      symptoms of patients with FA.

      The second objectives of the trial are:

        1. To evaluate the safety and the risk of hypercalcemia with the treatment with low dosis
           of Calcitriol (0.25mcg of Calcitriol every 24h) in patients with FA.

        2. To measure de change in the Frataxin's levels during the treatment with Calcitriol.

        3. To evaluate the effects of Calcitriol in the daily life activities and the life quality
           of the patients with FA.

      Sample size: The number of participants needed to compleat the trial is 20. Duration: The
      duration of the trial is one year

      Procedure:

        -  Before taking part in the study, it will be ensured that participants fulfill all the
           inclusion criteria with a detailed questionnaire.

        -  During the clinical trial the following test will be done: 4 electrocardiogram, 5 blood
           analysis to control de risk of hypercalcemia and to measure the frataxin's levels, and 3
           full neurological examinations.

      Post trial treatment details:

      The patients who wish to continue with the treatment will be allowed to do so, at least until
      the results of the comparison of the basal neurological evaluation with the second and the
      final neurological evaluation are obtained.

      If the results are positive, the treatment will be continued with regular blood tests
      controls.

      If the results don't demonstrate a statistically significant effect, the treatment will be
      interrupted in all patients.
    

Intervention name(s): Calcitriol; Blood analysis for frataxin's level measurement; Blood analysis for hypercalcemia's control
Intervention type(s): Drug; Other; Diagnostic Test
Intervention description(s): Administration of Calcitrol 0.25mcg/24h for a year in Friedreich's Ataxia patients (n=20); Five blood analysis in Friedreich's Ataxia patients: before starting the treatment, and after fifteen days, 4 months, 8 months and 12 months of the treatment.
To validate the Frataxin's levels measurement, a blood analysis will also be done in two kind of controls for every Friedreich's Ataxia patient, only once at the beginning of the trial.
The control groups will be composed by:
Heterozygous Ataxia's Friedreich controls (a close relative of the patient, either a heterozygous sibling or one of the parents)
Age- and gender-matched controls (supposedly non-heterozygous).; Five blood analysis in Friedreich's Ataxia patients for monitoring the hypercalcemia risk (with measurement of Calcium, D Vitamin, renal function, albumin, protein, phosphate, sodium and potassium) Before starting the treatment, and after fifteen days, at 4 months, 8 months and 12 months of the treatment.
Other intervention name(s): Rocaltrol
Intervention MeSH terms: Calcitriol
Intervention model: Single Group Assignment
Intervention model description: Evaluate the effects of Calcitriol 0.25mcg/24h administered during a year in the neurological symptoms of patients with Friedreich's Ataxia
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: FA