Western Institutional Review Board approves Dose Comparison
IFN-B1a to determine effects upon Endocrine Function, with Derek
Smith, MD as Principal Investigator.
Effects of IFN-B1a treatment of MS upon steroid hormone production
Protocol short title/ identifier:
IFN-B1a effects on steroids
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.
To screen for effects of IFN-B1a treatment on steroid production
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
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.
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.
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
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.