Efficacy of EGb761 in Patients Suffering From Friedreich Ataxia

Phase 2

Completed

Conditions: Friedreich Ataxia

Interventions: Drug: EGb 761 120 mg
Drug: Placebo

Registration Number: NCT00824512

Lead Sponsor: Ipsen

Brief Summary: The purpose of this protocol is to determine the efficacy of EGb 761 120 mg bid versus placebo in patients suffering from Friedreich Ataxia

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 22

Inclusion Criteria

Friedreich ataxia diagnosis confirmed by evidenced mutation expansion of Frataxin gene
Ambulatory patient, with depressed tendon reflexes and pyramidal syndrome associated or not to a loss of position or vibration senses or dysarthria
Patient able to perform the tests of the study

Exclusion Criteria

Severe cardiac disease as assessed by echocardiography performed at least within 6 months before screening or during the wash out period (4 weeks)
Absolute contra-indication to Nuclear Magnetic Resonance spectroscopy(NMR) examination: iron and any magnetic objects implanted in the whole body, e.g. some neurostimulators, cardiac pace-makers, vascular clips and other implanted orthopaedic prosthesis
Patient who did not deplete at baseline phosphocreatine (PCr) pool by more than 30 % during the exercise bout
Any continuous use of the following forbidden medications:
other antioxidant such as idebenone, coenzyme Q, vitamin E/C taken for less than 4 weeks prior study treatment start (ie for antioxidant drugs a mandatory wash-out period of 4 weeks prior study drug start has to be observed),
any other vasodilators
tranquilizer such as benzodiazepine, meprobamate or buspirone, and/or antidepressant (only one), at non stable dose

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EGb 761® 120 mg	EGb 761 120 mg	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Creatine Rephosphorylation Rate Post Exercise	Baseline (Week 0) to Week 12	Creatine Rephosphorylation Rate post exercise measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy and calculated with correction according to muscular pH.

Secondary Outcome Measures

Name	Time	Method
Muscle Reoxygenation Rate Post Exercise.	Baseline (Week 0) to Week 12	Muscle reoxygenation rate post exercise was assessed using Myoglobin Hydrogen-1 Nuclear Magnetic Resonance spectroscopy.
Perfusion-time Integral During the First 9 Minutes Post Exercise.	Baseline (Week 0) to Week 12	The integral of 'peak perfusion' over a period of 9 minutes post exercise.
Developed Force During the Exercise Bout	Baseline (Week 0) to Week 12	Developed force during the exercise bout measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy
Metabolism Efficacy Index	Baseline (Week 0) to Week 12	The metabolism efficacy index was derived as Normalised work x creatine phosphorylation rate (sec-1). \[Normalised work was derived as Work developed during the exercise/(60 X Maximum cross section of muscle-1100)\]. Greater values of Metabolism Efficacy index indicate improvement in skeletal muscle energetics while lower values indicate the reverse. Negative values obtained using the formula indicated severe levels of muscle weakness.
International Cooperative Ataxia Rating Scale [ICARS] (Total Score)	Baseline (Week 0) to Week 12	The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales (i.e. Posture and gait disturbances, Kinetic functions, Speech disorders, \& Oculomotor disorders). Scores for each subscale quantify the extent of ataxia in each clinically important area and subscale scores are also summed to give a total score ranging from 0 to 100, with 100 indicative of the most severely affected outcome.
Peak Post Exercise Perfusion	Baseline (Week 0) to Week 12	Peak post exercise perfusion (mL/mn/100 g of tissue) was assessed using Arterial spin labelling combined with Nuclear Magnetic Resonance imaging.
Time to Peak Perfusion	Baseline (Week 0) to Week 12
ICARS (Posture and Gait Disturbance Score)	Baseline (Week 0) to Week 12	The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales including Posture and gait disturbances. Posture and gait disturbances score range from 0 to 34 (Higher scores indicate higher levels of impairment).
Muscle Trophicity: Maximum Cross Section of Muscle	Baseline (Week 0) to Week 12	Muscle trophicity measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy and calculated based on maximum cross section of muscle (cm\^2)
Normalised Work Developed During the Exercise	Baseline (Week 0) to Week 12	Normalised work developed during the exercise was derived as Work developed during the exercise/(\[60 X Maximum cross section of muscle\]-1100). Normalised work measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy.
ICARS (Kinetic Function Score)	Baseline (Week 0) to Week 12	The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales including Kinetic Function. Kinetic Function score range from 0 to 52 (Higher scores indicate higher levels of impairment).
ICARS (Speech Disorders Score)	Baseline (Week 0) to Week 12	The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales including Speech Disorders. Speech Disorders Score range from 0 to 8 (Higher scores indicate higher levels of impairment).
ICARS (Oculomotor Disorders Score)	Baseline (Week 0) to Week 12	The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales including Oculomotor Disorders. Oculomotor Disorders score range from 0 to 6 (Higher scores indicate higher levels of impairment).
Timed 25-foot Walk Test	Baseline (Week 0) to Week 12
Nine Hole Peg Test (Dominant Hand)	Baseline (Week 0) to Week 12	The nine hole peg test was used to assess cognitive function and in particular, fine motor coordination. The patient was asked to place nine pegs in nine holes and was scored on the amount of time it took to place and remove all nine pegs.
Nine Hole Peg Test (Nondominant Hand)	Baseline (Week 0) to Week 12	The nine hole peg test was used to assess cognitive function and in particular, fine motor coordination. The patient was asked to place nine pegs in nine holes and was scored on the amount of time it took to place and remove all nine pegs.
Visual Assessment Scale (VAS) of Global Impression - Parents	Baseline (Week 0) to Week 12	The VAS used a 10-cm scoring scale in which values were reported in mm such that 0=bad and 100=good. Total score range on VAS is from 0 to 100.
Visual Assessment Scale (VAS) of Global Impression - Investigator	Baseline (Week 0) to Week 12	The VAS used a 10-cm scoring scale in which values were reported in mm such that 0=bad and 100=good. Total score range on VAS is from 0 to 100.
Choice Reaction Time Test- Reaction Time	Baseline (Week 0) to Week 12	The choice reaction time test was used to assess cognitive functioning. On random presentation of one of six signal lights, the patient was asked to respond as quickly and accurately as possible by removing their index finger of the dominant hand from the bottom key and pressing whichever of the top six keys was indicated by the signal. Reaction time was the time elapsed between the presentation of the stimulus and the release of the finger and movement time was defined as the time elapsed between release of the finger and pressure of the second key.
Choice Reaction Time Test- Movement Time	Baseline (Week 0) to Week 12	The choice reaction time test was used to assess cognitive functioning. On random presentation of one of six signal lights, the patient was asked to respond as quickly and accurately as possible by removing their index finger of the dominant hand from the bottom key and pressing whichever of the top six keys was indicated by the signal. Reaction time was the time elapsed between the presentation of the stimulus and the release of the finger and movement time was defined as the time elapsed between release of the finger and pressure of the second key.
Visual Assessment Scale (VAS) of Global Impression - Patient	Baseline (Week 0) to Week 12	The VAS used a 10-cm scoring scale in which values were reported in mm such that 0=bad and 100=good. Total score range on VAS is from 0 to 100.