Progression Rate of MSA Under EGCG Supplementation as Anti-Aggregation-Approach

• Status: Completed
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

Summary

MSA is a rapidly progressive disorder with an average survival time of about 7 years after the first clinical manifestation. No potent symptomatic treatment is currently available. A disease-modifying therapy does not exist either. The growing understanding in recent years of the underlying pathological mechanisms of the disease allows the development of new treatment options that have a modifying effect on the disease progression. Therefore, treatments are urgently required that effect the central underlying pathological mechanism, which appears to be the intracellular aggregation of toxic oligomers of α-synuclein.

EGCG, a polyphenol found in green tea, has shown to inhibit the formation of toxic α-synuclein oligomers in vitro and has shown to transform α-synuclein-oligomers in non-toxic oligomer species. There is also evidence for a neuroprotective effect in MPTP-mouse models of PD and is an antioxidant and iron chelator. There are currently 63 clinical studies (http://clinicaltrial.gov) in which EGCG was applied for various indications, such as Multiple Sclerosis, various forms of cancer and Huntington's disease. All of which have shown good tolerability and safety with the applied doses of EGCG of up to 1200 mg per day, demonstrating the safety of the drug under controlled clinical conditions (see 5.3.1 for hepatotoxicity in uncontrolled conditions).

These data provide a solid rationale for testing in a clinical trial if supplementation of EGCG can interfere with the core disease mechanism in MSA and consequently retard the clinical progression of the MSA-related disability.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dr. Johannes Levin
• Collaborators: Deutsche Parkinson Vereinigung; Deutsche Stiftung Neurologie; German Center for Neurodegenerative Diseases (DZNE); German Foundation for Neurology; ParkinsonFonds Deutschland gGmbH
• Treatments: Epigallocatechin gallate; Neuroprotective Agents

Criteria

Inclusion 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

1. drugs acting against Parkinsonism (e.g. Levodopa, Dopamine-Agonists, Amantadine and MAO-B-Inhibitors)

2. drugs acting against autonomic dysfunction (e.g. ephedrin, midodrin, fludrucortison, octreotide, desmopresin, oxybutinine)

3. 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.

Exclusion Criteria:

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 investigational 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 plasmocytoma.

13. Anemia at Screening (Hb < 10g/dl)

14. Other severe medical conditions upon discretion of the LKP