Clinical trial NCT00631202: Efficacy of Epoetin Alfa in Patients With Friedreich's Ataxia
Official title: Single-Center, Open-Label, Sequential Trial to Test the Efficacy, Safety and Tolerability of Epoetin Alfa in Patients With Friedreich's Ataxia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Friedreich's Ataxia
Keywords: FRDA
Erythropoietin
Epoetin alfa
Lead sponsor: Federico II University
Sponsor class: OTHER
First posted: 2008-03-07
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Friedreich's ataxia is a rare genetic disorder characterized by severe neurological disability and cardiomyopathy. Friedreich's ataxia is the consequence of frataxin deficiency. Although several drugs have been proposed, there is no available treatment. It was recently demonstrated that erythropoietin can increase the intracellular levels of frataxin in an in-vitro model.

The present project is aimed at testing the possible therapeutic approach of erythropoietin, which is an already available and commercialized drug. The investigators will perform both in-vitro and in-vivo tests, in order to asses its efficacy and safety in patients. The results will be useful to plan further clinical trials.

Detailed description: Friedreich ataxia (FRDA) is an inherited recessive disorder characterized by progressive neurological disability. FRDA is the consequence of frataxin deficiency. Although several drugs have been proposed for FRDA, there is no available treatment. Recently it was shown that recombinant human erythropoietin (rhu-EPO) administration increases frataxin expression in cultured human lymphocytes of FRDA patients. It is therefore of primary importance to test extensively rhu-EPO's ability in increasing frataxin levels in-vitro and in-vivo. In addition rhu-EPO is an already available and commercialized drug approved for the treatment of anaemia associated with chronic renal disease, heart failure and cancer. Towards this overall purpose, we will perform an acute clinical trial in FRDA patients with rhu-EPO and will assess its effect in-vivo on frataxin expression. In addition, rhu-EPO's safety in FRDA patients based on laboratory parameters and neurological indexes will be tested. The results will be useful to gain new insight in the role of rhu-EPO in FRDA, and in the future, it may be useful to plan further clinical trials.

Eligibility criteria: Inclusion Criteria:

* Molecular diagnosis of FA based on a homozygous GAA expansion within the FRDA with a triplet repeat sequence in the pathological range.
* Age \>18, \<50 years

Exclusion Criteria:

* Failure to meet one of the inclusion criteria
* Patients in treatment with Idebenone
* Wheelchair bound patients
* Significant renal, hepatic or haematological disease
* Positive history for arterial or venous thrombosis
* Acute diseases that might interfere with the study
* Positive history for arterial hypertension
* Present or programmed pregnancy
* Known hypersensitivity to study drug
* Other unacceptable concomitant medications (in particular agents thought to have a neuroprotective potential as tocopherol, amantadine, memantine, free radical scavengers).

Primary outcomes:
measure: Primary endpoint will be the frataxin level in PBMCs from patients at different timing from a single Epoetin alfa administration.
timeFrame: 0, 24, 48, 96 hours; 7, 15, 30, 60 days
Secondary outcomes:
measure: Echocardiography: Strain and strain rate after EPO administration at the highest study dose
timeFrame: 0, 30 days
measure: Safety laboratory parameters, adverse events and tolerability
timeFrame: 0, 7, 15, 30, 60 days
measure: International cooperative ataxia rating scale (ICARS).
timeFrame: 0, 7, 30 days
Other outcomes:
Locations:
city: Naples
country: Italy
facility: Dipartimento di Scienze Neurologiche
Study officials:
affiliation: Dipartimento di Scienze Neurologice, University "Federico II" Naples
name: Alessandro Filla, MD
role: STUDY_DIRECTOR
References: