Safety of Polyphenon E in Multiple Sclerosis Pilot Study

Safety and Neuroprotective Effects of Polyphenon E in Multiple Sclerosis

This study is an open label 6 month study. All subjects will be treated with Polyphenon E (400 mg EGCG twice a day) for six months. The main outcome of this pilot phase will be safety. Secondary outcomes are the change in NAA levels over 6 months as measured by MR-spectroscopy. NAA levels are a marker of neuronal function. We think that Polyphenon E will protect neurons and thus increase NAA levels.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Polyphenon E

Detailed Description

Additional clinical data include changes in EDSS, MS functional composite and cognitive testing.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana Health Sciences Center New Orleans

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of MS by McDonald criteria
• Relapsing-remitting MS or secondary progressive MS
• Stable therapy with Copaxone, for at least six months prior to inclusion in the study or no therapy for six months in subjects refusing therapy.
• EDSS Score less than or equal to 6.5 (able to walk about 20 meters without resting)
• Ages 18-60.
• Leukocytes ≥3,000/µL
• Absolute neutrophil count ≥1,500/µL
• Platelets ≥100,000/µL
• Total bilirubin ≤local upper limit of normal
• normal AST (SGOT) ALT (SGPT)
• normal serum Creatinine
• women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
• Ability to understand and the willingness to sign a written informed consent document.
• Willing to drink at most one cup of black tea and two cups of coffee per day, and abstain from drinking green tea or taking supplements containing green tea or green tea compounds, for the duration of the investigation.

Exclusion Criteria:

• MS relapse within the 30 days prior to enrollment.
• A primary progressive form of MS.
• Previous treatment prior to study entry as follows: complete radiation ablation of the bone marrow or anti-CD4 antibody treatment (Campath) at any time; mitoxantrone, cyclophosphamide, cyclosporin, Natalizumab or other immunomodulatory or immunosuppressant therapies except for Copaxone or methylprednisone for relapses within prior nine months.
• History of renal or liver disease.
• Consumption of green tea or supplements containing green tea or tea extract within 30 days prior to enrollment.
• Participants may not participate in any other clinical trial involving investigational agents during the study, or within six months prior to enrolling in the study.
• history of allergic reactions attributed to compounds of similar chemical or biologic composition to Polyphenon E, tea, or any of the inactive ingredients present in the active or placebo capsules, including gelatin.
• history of allergic reactions to gadolinium or any other condition contraindicated for MRI.
• Uncontrolled, clinically-relevant active illness (aside from MS) including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Any condition which would make the subject, in the opinion of the investigator, unsuitable for the study.
• Inability to complete the baseline MRI scan.
• Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Polyphenon E; Standarized green tea extract containing 50% EGCG	Drug: Polyphenon E; Polyphenon E capsules containing 200 mg of Epigallocachin-galleate. Two capsules twice a day.; Other Names: EGCG; Green tea extract

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Experiencing Serious Adverse Events	six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brain NAA Level as Measured by MR Spectroscopy	percent change from baseline to exit in NAA levels adjusted for creatine levels	6 months

Collaborators and Investigators

• Sponsor: Louisiana State University Health Sciences Center in New Orleans
• Collaborators: National Center for Complementary and Integrative Health (NCCIH)
• Investigators: Principal Investigator: Jesus F Lovera, MD, MSPH, LSUHSC

Publications and helpful links

General Publications

• Lovera J, Ramos A, Devier D, Garrison V, Kovner B, Reza T, Koop D, Rooney W, Foundas A, Bourdette D. Polyphenon E, non-futile at neuroprotection in multiple sclerosis but unpredictably hepatotoxic: Phase I single group and phase II randomized placebo-controlled studies. J Neurol Sci. 2015 Nov 15;358(1-2):46-52. doi: 10.1016/j.jns.2015.08.006. Epub 2015 Aug 7.
• Aktas O, Prozorovski T, Smorodchenko A, Savaskan NE, Lauster R, Kloetzel PM, Infante-Duarte C, Brocke S, Zipp F. Green tea epigallocatechin-3-gallate mediates T cellular NF-kappa B inhibition and exerts neuroprotection in autoimmune encephalomyelitis. J Immunol. 2004 Nov 1;173(9):5794-800. doi: 10.4049/jimmunol.173.9.5794.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: February 3, 2009
• First Submitted That Met QC Criteria: February 3, 2009
• First Posted (Estimate): February 4, 2009

Study Record Updates

• Last Update Posted (Estimate): June 27, 2013
• Last Update Submitted That Met QC Criteria: May 21, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: MRI; safety; Multiple sclerosis; open label; Polyphenon E; EGCG; NAA; N-acetyl-aspartate
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: K23AT004433-01 (U.S. NIH Grant/Contract); 1K23AT004433-01 (U.S. NIH Grant/Contract)