Clinical trial NCT00836719: Safety of Polyphenon E in Multiple Sclerosis Pilot Study
Official title: Safety and Neuroprotective Effects of Polyphenon E in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Sclerosis
Keywords: Multiple sclerosis
safety
open label
Polyphenon E
EGCG
NAA
N-acetyl-aspartate
MRI
Lead sponsor: Louisiana State University Health Sciences Center in New Orleans
Sponsor class: OTHER
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2009-02-04
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Experiencing Serious Adverse Events
timeFrame: six months
Secondary outcomes:
measure: Change in Brain NAA Level as Measured by MR Spectroscopy
timeFrame: 6 months
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Louisiana Health Sciences Center New Orleans
state: Louisiana
Study officials:
affiliation: LSUHSC
name: Jesus F Lovera, MD, MSPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.