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1/5/06 News item. - 10/17/05 News item.

Western Institutional Review Board approves Dose Comparison Trial of
IFN-B1a to determine effects upon Endocrine Function, with Derek Smith, MD as Principal Investigator.

Protocol Title:
Effects of IFN-B1a treatment of MS upon steroid hormone production

Protocol short title/ identifier:
IFN-B1a effects on steroids

Rationale:
In vitro and animal studies have consistently demonstrated that a wide array of steroid hormones can dramatically influence immune responses. MS is twice as prevalent in women versus men and it is generally thought that this relates to differences in the hormonal mileu which is mainly determined by production of various steroids. Specifically, estradiol has been proposed as an enhancer of cell-mediated immunity, while a male hormone DHEA may inhibit cell mediated immune function (2,5). Moreover, reports suggest that estriol may confer protection from MS attacks during pregnancy (1,3). Because these hormones appear to be important in regulation of immune responses regardless of gender, they will be measured in both men and women. Glucocorticoids have been a mainstay in the treatment of human autoimmune diseases for decades, and other steroid hormones are now either under investigation or in early phase clinical trials. B-IFN's cause a pronounced reduction in inflammation in RRMS. While many IFN early effects are understood, their precise mechanism of action in MS remains poorly defined. The effects on steroid hormone production are unknown and it is possible that such an effect could be central to the mechanism of action in MS. Gd+ and CU lesions on MRI will be used as a surrogate marker of disease activity in this study and will be measured at each dose. Because there is a several month delay before a course of IFN-B1a achieves its peak effect on new lesion formation, MRI's will be performed at months 3 and 12.

Objectives:
Primary:
To screen for effects of IFN-B1a treatment on steroid production

Secondary:
To find correlations between these effects and MS MRI activity

Subjects and Centers:
This would be a single center pre versus post treatment study which would enroll 12 women and 12 men

Inclusion/Exclusion Criteria:
RRMS patients not previously treated with IFN's would be enrolled. Patients with a history of depression or an endocrine dysfunction or disease would be excluded. Women on oral contraceptives, planning to become pregnant, or post-menopausal would be excluded.

Other Therapy:
NA

Study Design:
Patients will have baseline MRI and steroid measures performed at predefined timepoints. These will be repeated at 1 month , and at 12 months. Study duration will be one year.

Efficacy Measures:
Serum FSH*, LH*, PRL, ACTH, TSH, estradiol*, DHEA, DHEAS, testosterone, pregenenediol*, androstenedione,Vit D3, 24 hour urine cortisol (*to be measured on day 4 and mid-luteal in women) Brain MRI with gad, CU lesions, EDSS with FSS's, VAS for fatigue, stress All of the above will be measured at baseline, 3, 7, and 12 months

Safety:
It is not anticipated that there will be any safety concerns beyond those of standard practice

Decision Points/Statistical methods/Interim analysis:
This is a pilot study designed to screen for potentially interesting results. Any post-treatment result which shows a difference from baseline with p<0.05 by Student's T test would then be pursued in a follow-on study. All available data will be evaluated.