Safety Study of Carbamylated Erythropoietin to Treat Patients With the Neurodegenerative Disorder Friedreich's Ataxia
Summary
The primary purpose of the study is to determine whether carbamylated erythropoietin is a safe treatment for patients who suffer from Friedreich's Ataxia.
Description
Friedreich's Ataxia (FRDA) is a hereditary, progressive neurodegenerative disorder caused by mutations in the gene encoding frataxin. The mutation results in a severe reduction in levels of the mitochondrial protein, frataxin. A decline in frataxin levels and its associated consequences is believed to be the primary cause of symptoms in FRDA patients. The clinical symptoms of FRDA include progressive gait and limb ataxia, dysarthria, diabetes mellitus and hypertrophic cardiomyopathy. First symptoms usually appear between the age of 5 and 15 years. As the disease progresses the patient becomes confined to a wheel chair and at later stages the patients become increasingly incapacitated. There is currently no effective treatment for FRDA.
The naturally occurring hormone, erythropoietin (EPO), is able to protect various neuronal tissues from ischemic injury. Recombinant human erythropoietin (EPO) increases frataxin expression in lymphocytes from patients with FRDA. Also, EPO treatment of FRDA patients resulted in a favourable outcome compared to baseline as assessed by the levels of frataxin and biomarkers of oxidative stress. In a pilot study with EPO in FRDA patients, the treatment was well tolerated apart from the expected haematological (haematopoietic) side effects. Lu AA24493 (CEPO) is a modified (carbamylated) version of EPO, which is neuroprotective but without the haematopoietic side effects. Lu AA24493 is being developed for treatment of patients with FRDA.
Although the target for the non-haematological effects of Lu AA24493 (and EPO) is currently unknown, Lu AA24493 (CEPO) can protect cells and tissue from various types of injuries. Furthermore, in vitro Lu AA24493 (CEPO) increases the frataxin levels in lymphocytes from FRDA patients as well as from control patients. This study aims to evaluate the safety of 2 weeks treatment (6 doses, 3 doses per week) of CEPO in patients with FRDA and to explore efficacy by using neurological rating scales and by exploring levels of frataxin and biomarkers of oxidative stress.
Study Design
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Conditions
Friedreich's Ataxia
Intervention
Lu AA24493, Placebo
Location
IT001
Milano
Italy
20133
Status
Recruiting
Source
H. Lundbeck A/S
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01016366
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Friedreich Ataxia
An autosomal recessive disease, usually of childhood onset, characterized pathologically by degeneration of the spinocerebellar tracts, posterior columns, and to a lesser extent the corticospinal tracts. Clinical manifestations include GAIT ATAXIA, pes cavus, speech impairment, lateral curvature of spine, rhythmic head tremor, kyphoscoliosis, congestive heart failure (secondary to a cardiomyopathy), and lower extremity weakness. Most forms of this condition are associated with a mutation in a gene on chromosome 9, at band q13, which codes for the mitochondrial protein frataxin. (From Adams et al., Principles of Neurology, 6th ed, p1081; N Engl J Med 1996 Oct 17;335(16):1169-75) The severity of Friedreich ataxia associated with expansion of GAA repeats in the first intron of the frataxin gene correlates with the number of trinucleotide repeats. (From Durr et al, N Engl J Med 1996 Oct 17;335(16):1169-75)
Ataxia
Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions.
Therapeutic Misconception
Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.
Placebo Effect
An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.
Cerebellar Ataxia
Incoordination of voluntary movements that occur as a manifestation of CEREBELLAR DISEASES. Characteristic features include a tendency for limb movements to overshoot or undershoot a target (dysmetria), a tremor that occurs during attempted movements (intention TREMOR), impaired force and rhythm of diadochokinesis (rapidly alternating movements), and GAIT ATAXIA. (From Adams et al., Principles of Neurology, 6th ed, p90)
Clinical Trials
Pilot Study of Varenicline (Chantix®) in the Treatment of Friedreich's Ataxia
The purpose of this study is to determine if varenicline is effective in treating symptoms of Friedreich's ataxia.
Efficacy of EGb761 in Patients Suffering From Friedreich Ataxia
The purpose of this protocol is to determine the efficacy of EGb 761 120 mg bid versus placebo in patients suffering from Friedreich Ataxia
Efficacy of Epoetin Alfa in Patients With Friedreich's Ataxia
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 s...
The purpose of this trial is to study the efficacy, safety and tolerability of idebenone in 12 months of treatment in children and adults with Friedreich's Ataxia. This is a randomised pla...
Iron-Chelating Therapy and Friedreich Ataxia
Friedreich ataxia, an autosomal recessive condition, ascribed to frataxin gene expansion, has been shown to result from an iron- induced injury to the mitochondrial respiratory chain. Buff...
PubMed Articles
Friedreich's ataxia is a multisystem disorder of mitochondrial function affecting primarily the heart and brain. Patients experience a severe cardiomyopathy that can progress to heart failure and deat...
Longitudinal change in dysarthria associated with Friedreich ataxia: a potential clinical endpoint.
CNS functions that show change across short periods of time are particularly useful clinical endpoints for Friedreich ataxia. This study determined whether there is measurable acoustical change in the...
Getting to the core of repeat expansions by cell reprogramming.
In this issue of Cell Stem Cell, Ku et al. (2010) demonstrate that iPSCS derived from Friedreich's ataxia patients exhibit expansion of the causative (GAA)(n) repeat, consistent with the repeat insta...
Friedreich ataxia: The vicious circle hypothesis revisited.
ABSTRACT: Friedreich ataxia, the most frequent progressive autosomal recessive disorder involving the central and peripheral nervous system, is mostly associated with an unstable expansion of GAA trin...
Neuroanatomical Correlates of Depression in Friedreich's Ataxia: a Voxel-Based Morphometry Study.
Affective disorders have been increasingly recognized in neurodegenerative diseases and often result in poor quality of life. However, the frequency, clinical relevance, and anatomical substrate of de...
