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

This study has been terminated.
(Unusual high frequency of elevated liver function tests.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jesus Lovera MD, Louisiana State University Health Sciences Center in New Orleans
ClinicalTrials.gov Identifier:
NCT01451723
First received: October 11, 2011
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Drug: Polyphenon E
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 2 Randomized Placebo Controlled Trial of Polyphenon E in MS

Resource links provided by NLM:


Further study details as provided by Louisiana State University Health Sciences Center in New Orleans:

Primary Outcome Measures:
  • Rate of Change in NAA Levels Adjusted for Water Content. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Brain Atrophy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Difference between the two groups in brain atrophy as measured by SIENA


Enrollment: 11
Study Start Date: July 2011
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Polyphenon E 400mg twice a day
Two capsules of Polyphenon E containing 200mg of EGCG each taken twice a day with food.
Drug: Polyphenon E
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.
Other Names:
  • EGCG
  • epigallocatechin gallate
  • Green tea extract
Placebo Comparator: Placebo
Matching placebo capsules.
Other: Placebo
Matching placebo capsules

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

    1. Leukocytes ≥3,000/µL
    2. Absolute neutrophil count ≥1,500/µL
    3. Platelets ≥100,000/µL
    4. Total bilirubin ≤local upper limit of normal
    5. AST (SGOT) ≤local upper limit of normal
    6. ALT (SGPT) ≤local upper limit of normal
    7. 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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01451723

Locations
United States, Louisiana
LSu Health Sciences Center
New Orleans, Louisiana, United States, 70112
Sponsors and Collaborators
Louisiana State University Health Sciences Center in New Orleans
Investigators
Principal Investigator: Jesus F Lovera, MD LSUHSC-New Orleans
  More Information

Additional Information:
No publications provided

Responsible Party: Jesus Lovera MD, MD, MsPH, Louisiana State University Health Sciences Center in New Orleans
ClinicalTrials.gov Identifier: NCT01451723     History of Changes
Other Study ID Numbers: K23 AT004433-02, K23AT004433-02, K23AT004433
Study First Received: October 11, 2011
Results First Received: December 10, 2013
Last Updated: January 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Louisiana State University Health Sciences Center in New Orleans:
Multiple Sclerosis
Polyphenon E
Green tea
EGCG
Epigallocatechin-galleate
Placebo
Randomized controlled trial

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Epigallocatechin gallate
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Antimutagenic Agents
Anticarcinogenic Agents
Antineoplastic Agents
Therapeutic Uses
Neuroprotective Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 16, 2014