Double blind, randomised, prospective placebo controlled parallel group phase III study to investigate the Effect of EGCG supplementation on disease progression of patients with Multiple System Atrophy (MSA)
- Conditions
- G23.2G23.3Multiple system atrophy, parkinsonian type [MSA-P]Multiple system atrophy, cerebellar type [MSA-C]
- Registration Number
- DRKS00005610
- Lead Sponsor
- Klinikum der Universität München, Campus Großhadern
- Brief Summary
please also see abstract of the original paper by Levin et al, Lancet Neurology 2019
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 92
Subjects can be included if they meet the following criteria:
1.„clinical possible or „clinical probable MSA (Gilman et al., Neurology, 2008 26;71:670-6)
2.Hoehn & Yahr stage I – III
3.A stable regimen for at least 1 month prior to V1 and willingness / no fore-seeable need to change the regimen throughout the 52 week follow-up pe-riod for
a.drugs acting against Parkinsonism (e.g. Levodopa, Dopamine-Agonists, Amantadine and MAO-B-Inhibitors)
b.drugs acting against autonomic dysfunction (e.g. ephedrin, midodrin, fludrucortison, octreotide, desmopresin, oxybutinine)
c.antidepressant and antidementive drugs.
4.No regular consumption of EGCG, green tea, or more than two cups of black tea per day
5.Capability and willingness to give written informed consent indicating that the subject has been informed of and understood all aspects pertinent to the study
6.Capability and willingness to comply with the procedures of the study
7.Contraception by adequate contraceptive methods (oral, injected or im-planted hormonal contraceptive methods, intrauterine pessar, sterilisation or real abstinence) in all female patients with childbearing potential
8.Absence of liver disease documented by transaminases and bilirubin below 2-folds of the upper normal level.
Subjects will not be included if any of the following criteria applies:
1.Hoehn & Yahr stage > 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 and bilirubin above 2-folds of the upper normal level or regular intake of hepatotoxic drugs
4.Known hypersensitivity to EGCG or to drugs with similar chemical structure
5.Participation in another clinical trial involving administration of an investiga-tional medicinal product within 1 month prior to V1
6.A physical or psychiatric condition, which at the investigator’s discretion may put the subject at risk, may confound the trial results, or may interfere with the subject’s participation in this clinical trial
7.Persistent abuse of medication, drugs or alcohol
8.Consumption of > 500 ml grapefruit juice per day (leading to inhibition of cytochrome P-450 isoenzyme 3A4, which may be involved in degradation of EGCG).
9.Current or planned pregnancy or breast feeding in females
10.Females of childbearing potential, who are not using medically reliable methods of contraception for the entire study duration (such as oral, inject-able, or implantable contraceptives, or intrauterine contraceptive devices).
11.Intake of COMT-inhibitors (e.g. Entacapone, Tolcapone)
12.Current or planned therapy with Bortezomib and/ or history of plasmocyto-ma.
13.Anemia at Screening (Hb < 10g/dl)
14.Other severe medical conditions upon discretion of the LKP
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 (52 weeks), (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 Outcome Measures
Name Time Method Clinical safety and tolerability of EGCG (physical and neurological examination, laboratory parameters, adverse events, vital signs, drop-out rates, survival rates and survival time) during the EGCg administration phase (verum group) of 48 weeks.<br>To assess the efficacy of EGCG vs. Placebo to reduce the disease progression from V1 to V7 (52 weeks) the following parameters are of interest: <br>- UMSARS total score<br>- clinical global impression (CGI)<br>- global and regional cerebral atrophy (3D MP-RAGE MRI volumetry, 3D FLAIR).<br>- global and regional cerebral iron deposition in pons and striatum (T2* MRI).<br>To assess any effect of EGCG vs. Placebo on the evolution of the above mentioned parameters during the wash-out phase (from V6 to V7; 4 weeks) to explore possible symptomatic effects.<br>