Multiple Sclerosis
Conditions
Keywords
Multiple sclerosis, safety, open label, Polyphenon E, EGCG, NAA, N-acetyl-aspartate, MRI
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.
Interventions
DRUGPolyphenon E
Polyphenon E capsules containing 200 mg of Epigallocachin-galleate. Two capsules twice a day.
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Louisiana State University Health Sciences Center in New Orleans
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Experiencing Serious Adverse Events | six months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brain NAA Level as Measured by MR Spectroscopy | 6 months | percent change from baseline to exit in NAA levels adjusted for creatine levels |
Countries
United States
Participant flow
Recruitment details
Recruitment started in 9/2009 and ended 4/2010. Subjects were recruited from the LSU MS Clinic and from the community. Advertisements were placed in the quarterly MS Society newsletter and email list.
Participants by arm
| Arm | Count |
|---|---|
| Polyphenon E Standarized green tea extract containing 50% EGCG
Polyphenon E : Polyphenon E capsules containing 200 mg of Epigallocachin-galleate.
Two capsules twice a day. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Polyphenon E |
|---|---|
| Age Continuous | 45 years |
| Disease duration | 14 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Expanded Disability Status Scale | 4 points |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 1 Participants |
| Type of MS Relapsing Remitting | 9 participants |
| Type of MS Secondary Progressive | 1 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Number of Participants Experiencing Serious Adverse Events
Time frame: six months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polyphenon E | Number of Participants Experiencing Serious Adverse Events | 0 participants |
Secondary
Change in Brain NAA Level as Measured by MR Spectroscopy
percent change from baseline to exit in NAA levels adjusted for creatine levels
Time frame: 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Polyphenon E | Change in Brain NAA Level as Measured by MR Spectroscopy | 10 percentage change from baseline |
Comparison: N-Acetylaspartate acid (NAA) levels were measured at baseline and exit (6 months). Voxels with less than 30% error in NAA and Creatine (Cre) were used.NAA, Cre and Proton Density were log transformed.p-value: <0.0195% CI: [3.4, 16.2]Mixed Models Analysis