Phase 3 N=92 Randomized Quadruple-blind Treatment

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

Multiple System Atrophy

Bottom Line

View on ClinicalTrials.gov: NCT02008721 ↗

Enrolled (actual)

Serious AEs

28.3%

Results posted

Mar 2024

Primary outcome: Primary: Change of Score in Motor Examination (ME) of the Unified MSA Rating Scale (UMSARS-ME) From V1 to V7. — 5.66; 6.60 score on a scale — p=0.51

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: EGCG as putative neuroprotective agent (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Dr. Johannes Levin
Primary completion: Sep 2016

Outcome Measures

Outcome	Result	p-value
PRIMARY Change of Score in Motor Examination (ME) of the Unified MSA Rating Scale (UMSARS-ME) From V1 to V7.	5.66; 6.60	0.51
SECONDARY Possible Symptomatic Effects of EGCG vs. Placebo Measured by the Change in the UMSARS - ME in the Wash-out Phase (From V6-V7)	0.68; 0.49	0.82
SECONDARY Change in the UMSARS Total Score From V1 to V7	10.33; 10.35	0.99
SECONDARY Possible Symptomatic Effects of EGCG vs. Placebo Measured by the UMSARS Total Score From V6 to V7 (During the Washout Phase)	0.70; -0.29	0.43
SECONDARY Percentage of Striatal Volume Loss in MRI (3D MP-RAGE MRI Volumetry, 3D FLAIR) From Baseline to V7 as Effect of Treatment (Epigallocatechin Gallate vs Placebo)	-0.029; -0.064	—
SECONDARY Clinical Safety and Tolerability of EGCG Measured by Death Rates	4; 2	—
SECONDARY Effect of Treatment (Epigallocatechin Gallate vs Placebo) on Safety and Tolerability: Discontinuation Rates Because of Hepatotoxicity	2; 0	—
SECONDARY Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 1	2; 1; 1; 0; 8; 6	—
SECONDARY Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 5	1; 0; 1; 0; 6; 5	—
SECONDARY Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 6	1; 0; 1; 0; 6; 3	—
SECONDARY Number of Participants Achieving Each Clinical Global Impression of Severity (CGI-S): Illness Level at Visit 7	0; 0; 1; 0; 2; 3	—
SECONDARY Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Improvement Level at Visit 7 Compared to the Baseline Visit	0; 0; 0; 0; 4; 5	—
SECONDARY Number of Participants Achieving Each Clinical Global Impression of Improvement (CGI-I): Efficacy Index (Therapeutic Effect of Treatment With Medication and Associated Side Effects) at Visit 7 Compared to the Baseline Visit	0; 1; 1; 0; 1; 1	—

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.

Eligibility Criteria

Inclusion Criteria

"clinical possible" or "clinical probable" MSA (Gilman et al., Neurology, 2008 26;71:670-6)
Hoehn & Yahr stage I - III
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
drugs acting against Parkinsonism (e.g. Levodopa, Dopamine-Agonists, Amantadine and MAO-B-Inhibitors)
drugs acting against autonomic dysfunction (e.g. ephedrin, midodrin, fludrucortison, octreotide, desmopresin, oxybutinine)
antidepressant and antidementive drugs.
No regular consumption of EGCG, green tea, or more than two cups of black tea per day
Capability and willingness to give written informed consent indicating that the subject has been informed of and understood all aspects pertinent to the study
Capability and willingness to comply with the procedures of the study
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
Absence of liver disease documented by transaminases and bilirubin below 2-folds of the upper normal level.

Exclusion Criteria

Hoehn & Yahr stage > III (loss of postural reflexes, no independent walking possible, inability to stand unassisted, wheelchair-bound).
Neurodegenerative diseases other than MSA
Severe liver disease with elevation of transaminases and bilirubin above 2-folds of the upper normal level or regular intake of hepatotoxic drugs
Known hypersensitivity to EGCG or to drugs with similar chemical structure
Participation in another clinical trial involving administration of an investigational medicinal product within 1 month prior to V1
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
Persistent abuse of medication, drugs or alcohol
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).
Current or planned pregnancy or breast feeding in females
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).
Intake of COMT-inhibitors (e.g. Entacapone, Tolcapone)
Current or planned therapy with Bortezomib and/ or history of plasmocytoma.
Anemia at Screening (Hb < 10g/dl)
Other severe medical conditions upon discretion of the LKP

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02008721). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.