Please select the eligibility criteria that correspond to the clinical trial below.
Title: Impact of Vitamin A Supplementation on Disease Activity and Progression in Multiple Sclerotic (MS) Patients
Brief Summary: The aim of this study is the comparison between the effects of supplementation with 25000 IU preformed vitamin A (retinyl palmitate) or placebo for first 6 months and 10000 IU/day for next 6 months on disease activity and progression in patients with Multiple Sclerosis.


Options:
A: Inclusion Criteria:

A patient may be included if he/she;

* Is aged between 18 and 55 years (both included).
* Has multiple sclerosis according to the McDonald criteria (McDonald 2001)
* Has a stable disease during the last month period prior to inclusion, and a disability equivalent to EDSS of 5.5 or less (Kurtzke 1983).
* Has shown disease activity defined as at least one relapse or at least one new MRI lesion (T1 enhancing or T2 lesion - ref. McDonald criteria) during the year prior to inclusion.
* Is prepared to and considered able to follow the protocol and to attend the planned visits during the whole study period.
* Is using adequate contraceptive methods and has negative pregnancy test results (female of childbearing potential must).
* Has given written informed consent.

Exclusion Criteria:

A patient has to be excluded if he/she;

* Has received continuous for more than one-week treatment with unsaturated fatty acids (omega-3) within 3 months prior to inclusion in the study.
* Has an active RRMS disease that would strongly be recommended for standard immunomodulatory treatment by the treating neurologist.
* Has received treatment with interferon-beta or glatiramer acetate within 6 months prior to inclusion in the study.
* Has received treatment with lymphoid irradiation, mitoxantrone, cyclophosphamide or long-term glucocorticoids.
* Has received treatment with azathioprine, cyclosporine or other immunosuppressive agents within the year prior to inclusion in the study.
* Has received treatment with glucocorticoids or ACTH within two month prior to inclusion in the study.
* Has experienced a relapse within one month prior to the inclusion in the study.
* Has converted to secondary progressive MS.
* Has suffered from major depression or any other psychiatric disorder that would preclude safe participation in the protocol.
* Has diabetes mellitus.
* Has alcohol or drug abuse.
* Has cardiac insufficiency, cardiomyopathy, significant cardiac dysrhythmia, unstable or advanced ischemic heart disease (NYHA III or IV), or malignant hypertension.
* Has renal insufficiency.
* Has ASAT or ALAT \> 2,5 x normal upper limit.
* Has leukopenia \< 2500 leukocytes per µl or thrombocytopenia \<100 000 thrombocytes per µl.
* Has any systemic disease, which can influence his/her safety and compliance, or the evaluation of the disability.
* Has thromboembolic disease that needs anticoagulative treatment.
* Have formerly shown severe reactions against study drug, interferon-beta or gadolinium (MRI contrast).
* Is breastfeeding or is pregnant.
B: 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)
C: 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.
D: Inclusion Criteria:

* Patients who have used interferon beta in last 3 months
* Patients with 0-5 EDSS

Exclusion Criteria:

* Patients who have diseases which affect on Th1/Th2 balance such as asthma, active viral infections, and autoimmune diseases, OR

  * Patients who have allergy to vitamin A compounds, OR
  * Patients who have used vitamin supplements in last 3 months.

Answer: D