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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Ludwig-Maximilians - University of Munich
Sponsor:
Collaborators:
German Center for Neurodegenerative Diseases (DZNE)
Deutsche Parkinson Vereinigung
Deutsche Stiftung Neurologie
International Parkinson Fonds Germany GmbH
Taiyo international GmbH
Information provided by (Responsible Party):
Dr. Johannes Levin, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier:
NCT02008721
First received: December 8, 2013
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Multiple System Atrophy
Drug: EGCG as putative neuroprotective agent
Drug: Placebo
Phase 3

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: Treatment
Official Title: Double-blind, Randomised, Placebo-controlled Parallel Group Study to Investigate the Effect of EGCG Supplementation on Disease Progression of Patients With Multiple System Atrophy (MSA)

Resource links provided by NLM:


Further study details as provided by Ludwig-Maximilians - University of Munich:

Primary Outcome Measures:
  • motor examination (ME) of the Unified MSA Rating Scale (UMSARS-ME) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • UMSARS total score [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    To assess the efficacy of EGCG vs. Placebo to reduce the progression from V1 to V7 in UMSARS total score

  • clinical global impression [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    To assess the efficacy of EGCG vs. Placebo to reduce the progression from V1 to V7 in clinical global impression

  • global and regional cerebral atrophy (3D MP-RAGE MRI volumetry, 3D FLAIR) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    To assess the efficacy of EGCG vs. Placebo to reduce the progression from V1 to V7 in global and regional cerebral atrophy (3D MP-RAGE MRI volumetry, 3D FLAIR)

  • global and regional cerebral iron deposition in pons and striatum (T2* MRI) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    To assess the efficacy of EGCG vs. Placebo to reduce the progression from V1 to V7 in global and regional cerebral iron deposition in pons and striatum (T2* MRI)

  • Clinical safety and tolerability of EGCG [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Clinical safety and tolerability of EGCG (physical and neurological examination, laboratory parameters, adverse events, vital signs, drop-out rates, survival rates and survival time)

  • possible symptomatic effects EGCG vs. Placebo [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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) to explore possible symptomatic effects.


Other Outcome Measures:
  • Iron metabolism [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    To assess the efficacy of EGCG vs. Placebo to reduce the progression from V1 to V7 in Albumine, total protein, ferritin, iron, transferrin


Estimated Enrollment: 86
Study Start Date: January 2014
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: EGCG as putative neuroprotective agent
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
Drug: EGCG as putative neuroprotective agent
Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent
Other Name: Sunphenon EGCg
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo
Other Name: Placebo

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT02008721

Contacts
Contact: Johannes Levin, MD +49 89 7095 ext 2575 jlevin@med.uni-muenchen.de
Contact: Günter Höglinger, MD +49 7095 ext 8406 guenter.hoeglinger@dzne.lmu.de

Locations
Germany
Neurology Department, Ludwig-Maximilians University Recruiting
München, Bavaria, Germany, 81377
Contact: Kai Bötzel, MD    +49 89 7095 ext 3673    kboetzel@med.uni-muenchen.de   
Contact: Madeleine Schuberth, MD    +49 89 7095 ext 6675    madeleine.schuberth@med.uni-muenchen.de   
Principal Investigator: Johannes Levin, MD         
Sub-Investigator: Kai Bötzel, MD         
Sub-Investigator: Madelaine Schuberth, MD         
Department of Neurology, Klinikum rechts der Isar, Technische Universität München Recruiting
München, Bavaria, Germany, 81675
Contact: Günter Höglinger, MD    +49 89 7095 ext 8405    guenter.hoeglinger@dzne.de   
Contact: Sylvia Maass, MD    +49 89 7095 ext 8405    sylvia.maass@dzne.de   
Principal Investigator: Günter Höglinger, MD         
Sub-Investigator: Sylvia Maass, MD         
Heinrich-Heine-Universität, Neurologische Klinik Recruiting
Düsseldorf, Germany, 40225
Contact: Martin Südmeyer, MD    +49 - (0)211 - 8116756    Martin.Suedmeyer@med.uni-duesseldorf.de   
Contact: Alexandra Müller, PhD    +49 211 81-18075    Alexandra.Mueller@med.uni-duesseldorf.de   
Principal Investigator: Martin Südmeyer, MD         
Philipps Universität Recruiting
Marburg, Germany, 35043
Contact: Simone Brozat    +49-6421 -5865168    brozat@med.uni-marburg.de   
Contact: Evelyn Mahla    +49-(0)6421-58 65439    mahlae@med.uni-marburg.de   
Principal Investigator: Wolfgang Oertel, MD         
Sponsors and Collaborators
Dr. Johannes Levin
German Center for Neurodegenerative Diseases (DZNE)
Deutsche Parkinson Vereinigung
Deutsche Stiftung Neurologie
International Parkinson Fonds Germany GmbH
Taiyo international GmbH
Investigators
Principal Investigator: Johannes Levin, MD Ludwig Maximilians University, Department of Neurology
Principal Investigator: Günter Höglinger, MD Deutsches Zentrum für Neurodegenerative Erkrankungen e.V.
  More Information

Additional Information:
Publications:

Responsible Party: Dr. Johannes Levin, Sponsor delegated person, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT02008721     History of Changes
Other Study ID Numbers: PROMESA
Study First Received: December 8, 2013
Last Updated: May 22, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Ludwig-Maximilians - University of Munich:
Multiple System Atrophy
epigallocatechin gallate

Additional relevant MeSH terms:
Multiple System Atrophy
Shy-Drager Syndrome
Atrophy
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Hypotension
Vascular Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Epigallocatechin gallate
Neuroprotective Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Antimutagenic Agents
Anticarcinogenic Agents
Antineoplastic Agents
Therapeutic Uses
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 27, 2014