Trial Information

Mechanistic Study: Vascular Cells and the Pathogenesis od Systemic Sclerosis

The purpose of this study is to measure and characterize the circulating endothelial
progenitor cells from the blood of 30 participants and also to determine the extent of
vascular cell apoptosis and proliferation in cutaneous microvasculature in these
participants before and after the 2 SCOT treatment regimens.

Secondary objectives are:

1. To study the angiogenic response in SCID mice transplanted with SSc skin collected from
15 participants before and after the two treatment regimens.

2. To determine the molecular and cellular changes, including quantitative composition and
gene expression profiling occurring in the bone marrow of SCID mice transplanted with
SSc skin collected before and after the two treatment regimens.

The findings will be correlated with the primary endpoints of the SCOT study, as well as the
modified Rodnan skin score, which will help determine whether fibrosis in scleroderma
represents a default pathway resulting from vascular failure.

Recruitment for this study will be limited to participants who have elected to participate
in the SCOT study and have been randomized to one of the SCOT treatment arms. Participants
will be recruited after randomization to ensure balance on the two arms for this mechanistic
study and must agree to participate and sign an informed consent for this mechanistic study
prior to initiation of treatment on either arm. Thirty participants, 15 from each arm, will
be recruited for this sub-study. It will be conducted at the participating SCOT transplant
centers.

Two 3 mm punch skin biopsies will be obtained both at the pre-treatment visit and
approximately 12 months after the initiation of therapy with HDIT or pulse-dose
cyclophosphamide to coincide with the Month 14 SCOT study visit. Blood collection will also
occur at both of these sub-study visits (30 mL per timepoint) for EPC measurement and flow
cytometry.