Evaluation of the Effects of Calcitriol's in the Neurological Symptoms of Friedreich's Ataxia Patients

NCT04801303 | Completed Phase 4

• 2 other identifiers: IdIBGI2020-001092-32
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Friedreich Ataxia

Keywords

FA

Outcome Measures

Primary Outcomes (7)

• Changes in the SARA scale (Scale for the Assessment and Rating of Ataxia) in FA patients after a one-year treatment with Calcitriol.

  SARA is a scale which assesses a range of different impairments in cerebellar ataxia. The scale is made up of 8 items related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements and heel-shin test. The eight categories have an accumulative score ranging from 0 (no ataxia) to 40 (most severe ataxia). When completing the outcome measure each category is assessed and scored accordingly. Scores for the eight items range as follows: * Gait (0-8 points), * Stance (0-6 points), * Sitting (0-4 points) * Speech disturbance (0-6 points) * Finger chase (0-4 points) * Nose-finger test (0-4 points) * Fast alternating hand movement (0-4 points) * Heel-shin slide (0-4 points) Once each of the 8 categories have been assessed, the total is calculated to determine the severity of ataxia.

  At the beginning, and at the 6th and 12th month (one year) after the beginning of the trial.

• Changes in the 9-Hole Peg test in FA patients after a one-year treatment with Calcitriol.

  The 9-Hole Peg test is a quantitative assessment used to measure fingir dexterity. It is administered by asking the participant to take de pegs from a container, one by one, and place them into the holes on the boward, as quickly as possible. Participants must then remove the pegs from the holes, one by one, and replace them back into the container. The board should be placed at the client's midline, with the container holding the pegs oriented towards the hand being tested. Only the hand being evaluated should perform the test. Hand not being evaluated is permitted to hold the edge of the board in order to provide stability. Both hands will be assessed. Scores are recorded in seconds and are based on the time taken to complete the test activity, scoring better when less seconds are required to complete de test. Stopwatch should be started from the moment the participant touches the first peg until the moment the last peg hits the container.

  At the beginning, and at the 6th and 12th month (one year) after the beginning of the trial.

• Changes in the 8 meters walking test in FA patients after one year treatment with Calcitriol.

  The 8 meters waking test is used to asses walking speed in over a short distance of 8 meters. It is administered by asking the participant to walk through an 8 meteres lenght stright line as faster as posible. Scores are recorded in seconds and are based on the time taken to complete the test activity, scoring better when less seconds are required to complete de test. Stopwatch should be started from the moment the participant starts to walk until he reaches the final of the stright line.

  At the beginning, and at the 6th and 12th month (one year) after the beginning of the trial.

• Changes in the PATA rate test in FA patients after one year treatment with Calcitriol.

  PATA Rate Task is a quantitative test used to measure the severity of dysarthria. Participants are invited to repeat the syllables "PA-TA" as quickly as possible during a 10 seconds interval. They will do the same test twice, being the final score the average of the two attempts. The score consists in the number of correct repetition of both syllables, scoring better when they are able to say more correct repetitions of the syllables.

  At the beginning, and at the 6th and 12th month (one year) after the beginning of the trial.

• Changes in Barthel index for Activities of Daily Living in FA patients after one year treatment with Calcitriol.

  Barthel index is an objective, standardized tool for measuring functional status. The individual is scored in a number of areas depending upon independence of performance. The ten variables measured in the Barthel scale are: * Presence or absence of fecal incontinence * Presence or absence of urinary incontinence * Help needed with grooming * Help needed with toilet use * Help needed with feeding * Help needed with transfers (e.g. from chair to bed) * Help needed with walking * Help needed with dressing * Help needed with climbing stairs * Help needed with bathing The total score range from 0, that is equivalent to complete dependence, to 100, that is equivalent to complete independence.

  At the beginning, and at the 12th month (one year) after the beginning of the trial.

• Changes in SF36 questionnaire in FA patients after one year treatment with Calcitriol.

  The SF-36 questionnaire is a qualitiy life teast to assess the quality of life. It contains 36 questions that address different aspects related to the daily life of the person who fills in the questionnaire. These questions are grouped and measured in 8 sections that are evaluated independently. The 8 dimensions included in each section are: * Physical functioning. * Limitations due to physical problems. * Body pain. * Social functioning. * Mental health. * Limitations due to emotional problems. * Vitality, energy or fatigue. * General perception of health. The questionnaire questions ask for answers related to the previous month. The scores for each of the 8 dimensions of the SF-36 range between the values 0 and 100, with 100 being a result that indicates optimal health and 0 would reflect a very poor state of health.

  At the beginning, and at the 12th month (one year) after the beginning of the trial.

• Changes in Frataxin's levels during Calcitriol treatment..

  In FA patients will be done blood analysis to monitor de Frataxin's levels. To validate the Frataxin's levels measurement a blood analysis will also be done in two kind of controls for every FA patient: * One heterozygous FA control (a close relative of the patient, either an heterozygous sibling or one of the parents). * One age- and gender-matched control, supposedly non-heterozygous. The controls should not have any neurological or related with Calcium metabolism disease, or should not be under treatment with Calcium or D Vitamin.

  At the beginning, and at the 15th day, 4th month, 8th month and 12th month after the beginning of the trial.

Secondary Outcomes (3)

• Assessing the Calcitriol treatment's side effects with an hypercalcemia symptoms' questionnaire.

  At the 15th day, 4th month, 8th month and 12th month after the beginning of the trial.

• Assessing the Calcitriol treatment's hypercalcemia risk with an Electrocardiogram (ECG).

  At the beginning, and at the 15th day, 4th month, 8th month and 12th month after the beginning of the trial.

• Assessing the treatment's hypercalcemia risk with a blood test.

  At the beginning, and at the 15th day, 4th month, 8th month and 12th month after the beginning of the trial.

Study Arms (1)

Friedreich's Ataxia patients

EXPERIMENTAL

Friedreich's Ataxia patients that will receive treatment with Calcitrol 0.25mcg/24h for a year. During the clinical trial: * The effects of Calcitriol in the neurological symptoms of Friedreich's Ataxia patients will be evaluated before starting the treatment and after a year. The following scales will be used: SARA scale, 9-Hole Peg test, 8 meters walking test, PATA velocity test and Quality of life test with the SF36 questionnaire. * The changes in the Frataxin's levels during the treatment with Calcitriol will be measured: before starting the treatment, and after fifteen days, 4 months, 8 months and 12 months of the treatment.

Drug: Calcitriol; Other: Blood analysis for frataxin's level measurement; Diagnostic Test: Blood analysis for hypercalcemia's control

Interventions

Calcitriol DRUG

Administration of Calcitrol 0.25mcg/24h for a year in Friedreich's Ataxia patients (n=20)

Also known as: Rocaltrol

Friedreich's Ataxia patients

Blood analysis for frataxin's level measurement OTHER

1. 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. 2. 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).

Friedreich's Ataxia patients

Blood analysis for hypercalcemia's control DIAGNOSTIC_TEST

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.

Friedreich's Ataxia patients

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with Friedreich's Ataxia and confirmed genetic diagnosis with:
• Two pathological GAA triplet repeats in the gen FXN
• One pathological GAA triplet repeat and one point mutation in the gen FXN
• Patients between 16 and 65 years of age.
• To keep the walking ability, although an external aid is needed.
• Women with confirmed genetic diagnosis must use an effective contraceptive method during the trial.

You may not qualify if:

• Any neurological or other kind of disease that could interfere in the trial according to the investigator judgement.
• Severe visual loss.
• Severe auditory loss.
• Cognitive decline\*.
• Dementia or affective-cognitive cerebellar syndrome.
• Severe drug allergy.
• Cardiac disease:
• Ejection fraction \<40% \[N: 50-70%\]
• Heart failure \> 2 from NYHA (New York Heart Association) criteria.
• Significant valvular heart disease.
• Symptomatic coronary artery disease.
• Cardiac arrhythmia with hemodynamic compromise (atrial fibrillation).
• Prolonged immobilisation
• Legally or mentally incapacitated person.
• In women:

Sponsors & Collaborators

• Berta Alemany: lead
• Institut de Recerca Biomèdica de Lleida: collaborator
• Universitat de Lleida: collaborator
• Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta: collaborator

Study Sites (1)

Hospital Santa Caterina/Parc Martí i Julià

Salt, 17190, Spain

Location

Related Publications (1)

• Britti E, Delaspre F, Sanz-Alcazar A, Medina-Carbonero M, Llovera M, Purroy R, Mincheva-Tasheva S, Tamarit J, Ros J. Calcitriol increases frataxin levels and restores mitochondrial function in cell models of Friedreich Ataxia. Biochem J. 2021 Jan 15;478(1):1-20. doi: 10.1042/BCJ20200331.

  PMID: 33305808 RESULT

MeSH Terms

Conditions

Friedreich Ataxia

Interventions

Calcitriol; Hematologic Tests

Condition Hierarchy (Ancestors)

Spinocerebellar Degenerations; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Dihydroxycholecalciferols; Hydroxycholecalciferols; Cholecalciferol; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Berta Alemany Perna

  Hospital Universitari Josep Trueta/Hospital Santa Caterina, Girona/Salt, Spain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Evaluate the effects of Calcitriol 0.25mcg/24h administered during a year in the neurological symptoms of patients with Friedreich's Ataxia

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: March 17, 2021
• Study Start: August 25, 2021
• Primary Completion: September 30, 2022
• Study Completion: January 31, 2023
• Last Updated: October 23, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)