Efficacy of EGb761 in Patients Suffering From Friedreich Ataxia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ipsen
ClinicalTrials.gov Identifier:
NCT00824512
First received: January 15, 2009
Last updated: April 10, 2013
Last verified: April 2013
  Purpose

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


Condition Intervention Phase
Friedreich Ataxia
Drug: EGb 761 120 mg
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A Phase II, Randomised, Double Blind Study Assessing the Efficacy of EGb761 120mg Bid Versus Placebo in Patients Suffering From Friedreich Ataxia

Resource links provided by NLM:


Further study details as provided by Ipsen:

Primary Outcome Measures:
  • Creatine Rephosphorylation Rate Post Exercise [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
  • Perfusion-time Integral During the First 9 Minutes Post Exercise. [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    The integral of 'peak perfusion' over a period of 9 minutes post exercise.

  • Muscle Reoxygenation Rate Post Exercise. [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    Muscle reoxygenation rate post exercise was assessed using Myoglobin Hydrogen-1 Nuclear Magnetic Resonance spectroscopy.

  • Muscle Trophicity: Maximum Cross Section of Muscle [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    Developed force during the exercise bout measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy

  • Normalised Work Developed During the Exercise [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
  • Nine Hole Peg Test (Dominant Hand) [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Week 0) to Week 12 ] [ Designated as safety issue: No ]
    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.


Enrollment: 22
Study Start Date: June 2008
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EGb 761® 120 mg Drug: EGb 761 120 mg
EGb 761® 120 mg bid, orally for 12 to 14 weeks
Placebo Comparator: Placebo Drug: Placebo
Placebo 1 tablet BID, orally for 12 to 14 weeks

  Eligibility

Ages Eligible for Study:   12 Years to 22 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00824512

Locations
France
Hospital Necker Enfants Malades
Paris, France, 75015
Sponsors and Collaborators
Ipsen
Investigators
Study Director: Cécile Merdrignac, MD Ipsen
  More Information

No publications provided

Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT00824512     History of Changes
Other Study ID Numbers: 2-39-00240-133, 2007-005371-34
Study First Received: January 15, 2009
Results First Received: October 30, 2012
Last Updated: April 10, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Ataxia
Friedreich Ataxia
Stress, Psychological
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinocerebellar Degenerations
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Spinal Cord Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases
Behavioral Symptoms

ClinicalTrials.gov processed this record on July 22, 2014