Safety and Neuroprotective Effects of Polyphenon E in MS; Phase II

Study Overview
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Brief Summary
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The hypothesis is that Polyphenon E can protect brain cells in patients with Multiple Sclerosis. To test this hypothesis we are going to compare the changes in n-Acetyl-Aspartate (a chemical that reflects the number of neurons and their metabolism) over one year between people with MS treated with Polyphenon E at a dose of 400mg twice a day and people with MS treated with a matching sugar pill.

Detailed Description
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This will be a double blind placebo controlled trial of Polyphenon E as a treatment for MS. The primary outcome will be the changes in NAA levels over one year. Secondary outcomes will be changes in brain atrophy over one year. As an exploratory outcome we will correlate changes in NAA levels with free Plasma levels of EGCG 8 hours after the morning dose. Exploratory outcomes include disability progression by EDSS, MS functional composite components and a cognitive test battery.

Official Title
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Phase 2 Randomized Placebo Controlled Trial of Polyphenon E in MS

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Polyphenon E
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of MS by McDonald criteria Relapsing-remitting MS or secondary progressive MS Stable therapy with Copaxone, Rebif, Betaseron or Avonex 30 mcg for at least six months EDSS Score less than or equal to 7.0 Ages 18-60. Participants must have normal organ and marrow function as defined below: Leukocytes ≥3,000/µL Absolute neutrophil count ≥1,500/µL Platelets ≥100,000/µL Total bilirubin ≤local upper limit of normal AST (SGOT) ≤local upper limit of normal ALT (SGPT) ≤local upper limit of normal Creatinine ≤local upper limit of normal 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, Natalizumab or other immunomodulatory or immunosuppressant therapies except the DMT's included in the inclusion criteria and 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 women Any underlying predisposition to gastrointestinal bleeding (peptic ulcer disease, gastritis, diverticulitis, colitis, hemorrhoids)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Polyphenon E 400mg twice a day<br>Two capsules of Polyphenon E containing 200mg of EGCG each taken twice a day with food. | Drug: Polyphenon E<br>* Polyphenon E is a standardized green tea extract. For this study we will use capsules of Polyphenon E containing 200 mg of EGCG per capsule. Subjects will take two capsules twice a day with food.<br>* Other names: Green tea extract;|
| Placebo Comparator: Placebo<br>Matching placebo capsules. | Other: Placebo<br>* Matching placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Change in NAA Levels Adjusted for Water Content. | The rate of change will be calculated using all the time points available )baseline, 6 and 12 months) using a mixed model analysis with the Log NAA as the dependent variable and water content, %grey matter, %white matter, %CSF and % lesion volume as covariates. All the voxels available for each subject where estimates have a SD <30 will be used. A spatial anysotropic exponential covariance structure will be used. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain Atrophy | Difference between the two groups in brain atrophy as measured by SIENA | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Polyphenon E, Green tea, EGCG, Epigallocatechin-galleate, Placebo, Randomized controlled trial