Back to resultsEfficacy of EGb761 in Patients Suffering From Friedreich Ataxia
Primary Purpose
Friedreich Ataxia
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
EGb 761 120 mg
Placebo
Sponsored by
About this trial
This is an interventional supportive care trial for Friedreich Ataxia
Eligibility Criteria
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
Sites / Locations
- Hospital Necker Enfants Malades
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
EGb 761® 120 mg
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Time to Peak Perfusion
Perfusion-time Integral During the First 9 Minutes Post Exercise.
The integral of 'peak perfusion' over a period of 9 minutes post exercise.
Muscle Reoxygenation Rate Post Exercise.
Muscle reoxygenation rate post exercise was assessed using Myoglobin Hydrogen-1 Nuclear Magnetic Resonance spectroscopy.
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)
Developed Force During the Exercise Bout
Developed force during the exercise bout measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy
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.
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.
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.
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).
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).
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).
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).
Timed 25-foot Walk Test
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00824512
Brief Title
Efficacy of EGb761 in Patients Suffering From Friedreich Ataxia
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
June 2008 (undefined)
Primary Completion Date
October 2011 (Actual)
Study Completion Date
October 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ipsen
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Friedreich Ataxia
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
EGb 761® 120 mg
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
EGb 761 120 mg
Intervention Description
EGb 761® 120 mg bid, orally for 12 to 14 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo 1 tablet BID, orally for 12 to 14 weeks
Primary Outcome Measure Information:
Title
Creatine Rephosphorylation Rate Post Exercise
Description
Creatine Rephosphorylation Rate post exercise measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy and calculated with correction according to muscular pH.
Time Frame
Baseline (Week 0) to Week 12
Secondary Outcome Measure Information:
Title
Peak Post Exercise Perfusion
Description
Peak post exercise perfusion (mL/mn/100 g of tissue) was assessed using Arterial spin labelling combined with Nuclear Magnetic Resonance imaging.
Time Frame
Baseline (Week 0) to Week 12
Title
Time to Peak Perfusion
Time Frame
Baseline (Week 0) to Week 12
Title
Perfusion-time Integral During the First 9 Minutes Post Exercise.
Description
The integral of 'peak perfusion' over a period of 9 minutes post exercise.
Time Frame
Baseline (Week 0) to Week 12
Title
Muscle Reoxygenation Rate Post Exercise.
Description
Muscle reoxygenation rate post exercise was assessed using Myoglobin Hydrogen-1 Nuclear Magnetic Resonance spectroscopy.
Time Frame
Baseline (Week 0) to Week 12
Title
Muscle Trophicity: Maximum Cross Section of Muscle
Description
Muscle trophicity measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy and calculated based on maximum cross section of muscle (cm^2)
Time Frame
Baseline (Week 0) to Week 12
Title
Developed Force During the Exercise Bout
Description
Developed force during the exercise bout measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy
Time Frame
Baseline (Week 0) to Week 12
Title
Normalised Work Developed During the Exercise
Description
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.
Time Frame
Baseline (Week 0) to Week 12
Title
Metabolism Efficacy Index
Description
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.
Time Frame
Baseline (Week 0) to Week 12
Title
International Cooperative Ataxia Rating Scale [ICARS] (Total Score)
Description
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.
Time Frame
Baseline (Week 0) to Week 12
Title
ICARS (Posture and Gait Disturbance Score)
Description
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).
Time Frame
Baseline (Week 0) to Week 12
Title
ICARS (Kinetic Function Score)
Description
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).
Time Frame
Baseline (Week 0) to Week 12
Title
ICARS (Speech Disorders Score)
Description
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).
Time Frame
Baseline (Week 0) to Week 12
Title
ICARS (Oculomotor Disorders Score)
Description
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).
Time Frame
Baseline (Week 0) to Week 12
Title
Timed 25-foot Walk Test
Time Frame
Baseline (Week 0) to Week 12
Title
Nine Hole Peg Test (Dominant Hand)
Description
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.
Time Frame
Baseline (Week 0) to Week 12
Title
Nine Hole Peg Test (Nondominant Hand)
Description
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.
Time Frame
Baseline (Week 0) to Week 12
Title
Choice Reaction Time Test- Reaction Time
Description
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.
Time Frame
Baseline (Week 0) to Week 12
Title
Choice Reaction Time Test- Movement Time
Description
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.
Time Frame
Baseline (Week 0) to Week 12
Title
Visual Assessment Scale (VAS) of Global Impression - Patient
Description
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.
Time Frame
Baseline (Week 0) to Week 12
Title
Visual Assessment Scale (VAS) of Global Impression - Parents
Description
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.
Time Frame
Baseline (Week 0) to Week 12
Title
Visual Assessment Scale (VAS) of Global Impression - Investigator
Description
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.
Time Frame
Baseline (Week 0) to Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ipsen Medical Director
Organizational Affiliation
Ipsen
Official's Role
Study Director
Facility Information:
Facility Name
Hospital Necker Enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France
12. IPD Sharing Statement
Learn more about this trial
Efficacy of EGb761 in Patients Suffering From Friedreich Ataxia
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