Progression of patients with Multiple System Atrophy (MSA)
Conditions
Interventions
Trade Name: Sunphenon EGCg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: EGCG
CAS Number: 989-51-5
Current Sponsor code: EGCG
Other descriptive name: GREEN TEA LEAF
Concentration unit: mg mi
Sponsors
Hospital of the Ludwig-Maximilians-University of Munich
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Clinical signs of MSA. Diagnosis will be made for patients with „clinical possible“ or „clinical prob-able“ Multiple System Atrophy (MSA) according to the diagnostic criteria of Gilman et al. (Neurology 2008). 2. Stadium Hoehn & Yahr I – III 3. A stable regimen for at least 1 month prior to V1 and willingness / no foreseeable need to change the regimen throughout the the 52 week follow-up period for a. drugs acting against Parkinsonism (e.g. Levodopa, Dopamine-Agonists, Amantadine and MAO-B-Inhibitors) b. other CNS-active substances including antidepressants and antidementive drugs. c. drugs acting against autonomic dysfunction (e.g. ephedrin, midodrin, fludrucortison, octreo-tide, desmopresin, oxybutinine). 4.Capability and willingness to give written signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study 5. No regular consumption of green tea or EGCG 6. Not more than maximum of two cups black tea /day Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 86 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 86
Exclusion criteria
Exclusion criteria: 1. Clinical signs of MSA exceeding Stadium Hoehn and Yahr III (loss of postural reflexes, no independent walking possible, inability to stand unassisted, wheelchair-bound) 2. Neurodegenerative diseases other than MSA 3. Severe liver disease with elevation of transaminases above 5folds of the upper normal level or the in-take of hepatotoxic drugs 4. Known hypersensitivity to EGCG or substances with a similar chemical structure 5. Participation in another clinical trial involving administration of an investigational medicinal product within 30 days prior to V0. 6. Known or persistent abuse of medication, drugs or alcohol 7. Subjects with a physical or psychiatric condition that may put the subject at risk, confound trial results or may interfere with the subject’s participation in this clinical trial 8. Consumption of more than 500ml grapefruit juice/day (leading to inhibition of cytochrome P-450 isoen-zyme 3A4, which may be involved in degradation of EGCG) 9. Intake of COMT-Inhibitors (e.g. Entacapone, Tolcapone) 12. Current or planned therapy with bortezomib and/ or history of plasmocytoma 13. Anemia at Screening Visit (Hb < 10g/dl)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of EGCG vs. Placebo to reduce the progression in the motor examination (ME) of the Unified MSA Rating Scale (UMSARS-ME) from V1 to V7, (80% power, 5% P-level, 50% effect size, i.e. an expected mean yearly UMSARS-ME increase of 3.9 under verum treatment compared to 7.8 ± 6.8 (mean ± standard deviation) under Placebo-treatment. ;Secondary Objective: Clinical safety and tolerability of EGCG (physical and neurological examination, laboratory parameters, adverse events, vital signs, drop-out rates, survival rates and survival time). To assess the efficacy of EGCG vs. Placebo to reduce the progression from V1 to V7 the following parameters are of interest: - UMSARS total score - clinical global impression (CGI) - global and regional cerebral atrophy (3D MPRAGE MRI volumetry). - global and regional cerebral iron deposition in pons and striatum (T2* MRI). To assess any effect of ECGC vs. Placebo on the evolution of the above men-tioned parameters during the wash-out phase (from V6 to V7) to explore pos-sible symptomatic effects ;Primary end point(s): The change from V1 to V7 in UMSARS-ME comparing placebo vs. verum-treated patients;Timepoint(s) of evaluation of this end point: The change from V1 to V7 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Changes from V1 to V7 in the total UMSARS score comparing placebo vs. verum treated patients • Changes from V1 to V7 in CGI comparing placebo vs. verum treated patients • Changes from V1 to V7 in MRI parameters (global and regional atrophy / iron deposition) comparing placebo- vs. verum treated patients • Changes in UMSARS-ME, total UMSARS, GCI score, and MRI parameters (global and regional at-rophy / iron-deposition) from V6 to V7 comparing placebo- vs. verum-treated patients, to identify possible symptomatic effects. ;Secondary end point(s): Secondary efficacy endpoints: • Changes from V1 to V7 in the total UMSARS score comparing placebo vs. verum treated patients • Changes from V1 to V7 in CGI comparing placebo vs. verum treated patients • Changes from V1 to V7 in MRI parameters (global and regional atrophy / iron deposition) comparing placebo- vs. verum treated patients • Changes in UMSARS-ME, total UMSARS, GCI score, and MRI parameters (global and regional at-rophy / iron-deposition) from V6 to V7 comparing placebo- vs. verum-treated patients, to identify possible symptomatic effects. | — |
Countries
Germany
Contacts
Public ContactSponsor delegated person: Dr. Levin
Hospital of the Ludwig-Maximilians-University of Munich
Outcome results
None listed