Efficacy of EGb761 in Patients Suffering From Friedreich Ataxia

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

Official Title
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Efficacy of EGb761 120mg Bid Versus Placebo in Patients Suffering From Friedreich Ataxia. A 3 Month, Phase II, Randomised, Double Blind, Placebo Controlled, Parallel Group Clinical Study.

Conditions
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Friedreich Ataxia

Intervention / Treatment
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* Drug: EGb 761 120 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EGb 761® 120 mg<br> | Drug: EGb 761 120 mg<br>* EGb 761® 120 mg bid, orally for 12 to 14 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo 1 tablet BID, orally for 12 to 14 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Post Exercise Perfusion | Peak post exercise perfusion (mL/mn/100 g of tissue) was assessed using Arterial spin labelling combined with Nuclear Magnetic Resonance imaging. | Baseline (Week 0) to Week 12 | 
| Time to Peak Perfusion |  | Baseline (Week 0) to Week 12 | 
| Perfusion-time Integral During the First 9 Minutes Post Exercise. | The integral of 'peak perfusion' over a period of 9 minutes post exercise. | Baseline (Week 0) to Week 12 | 
| Muscle Reoxygenation Rate Post Exercise. | Muscle reoxygenation rate post exercise was assessed using Myoglobin Hydrogen-1 Nuclear Magnetic Resonance spectroscopy. | Baseline (Week 0) to Week 12 | 
| Muscle Trophicity: Maximum Cross Section of Muscle | Muscle trophicity measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy and calculated based on maximum cross section of muscle (cm^2) | Baseline (Week 0) to Week 12 | 
| Developed Force During the Exercise Bout | Developed force during the exercise bout measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy | Baseline (Week 0) to Week 12 | 
| Normalised Work Developed During the Exercise | 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. | Baseline (Week 0) to Week 12 | 
| Metabolism Efficacy Index | 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. | Baseline (Week 0) to Week 12 | 
| International Cooperative Ataxia Rating Scale [ICARS] (Total Score) | 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. | Baseline (Week 0) to Week 12 | 
| ICARS (Posture and Gait Disturbance Score) | 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). | Baseline (Week 0) to Week 12 | 
| ICARS (Kinetic Function Score) | 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). | Baseline (Week 0) to Week 12 | 
| ICARS (Speech Disorders Score) | 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). | Baseline (Week 0) to Week 12 | 
| ICARS (Oculomotor Disorders Score) | 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). | Baseline (Week 0) to Week 12 | 
| Timed 25-foot Walk Test |  | Baseline (Week 0) to Week 12 | 
| Nine Hole Peg Test (Dominant Hand) | 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. | Baseline (Week 0) to Week 12 | 
| Nine Hole Peg Test (Nondominant Hand) | 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. | Baseline (Week 0) to Week 12 | 
| Choice Reaction Time Test- Reaction Time | 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. | Baseline (Week 0) to Week 12 | 
| Choice Reaction Time Test- Movement Time | 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. | Baseline (Week 0) to Week 12 | 
| Visual Assessment Scale (VAS) of Global Impression - Patient | 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. | Baseline (Week 0) to Week 12 | 
| Visual Assessment Scale (VAS) of Global Impression - Parents | 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. | Baseline (Week 0) to Week 12 | 
| Visual Assessment Scale (VAS) of Global Impression - Investigator | 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. | Baseline (Week 0) to Week 12 |