Scleroderma: Cyclophosphamide or Transplantation (SCOT) Substudy 02

Status:	Completed
Conditions:	Neurology, Dermatology
Therapuetic Areas:	Dermatology / Plastic Surgery, Neurology
Healthy:	No
Age Range:	Any
Updated:	2/4/2013
End Date:	March 2012
Contact:	Keith Sullivan, MD
Email:	sulli025@mc.duke.edu
Phone:	866-909-SCOT

Mechanistic Study: Vascular Cells and the Pathogenesis od Systemic Sclerosis

The loss of blood vessels in the skin and other organs of patients with systemic sclerosis
(SSc) is a dominant feature of the disorder. The loss of capacity for the repair of blood
vessels, repair that requires the availability of endothelial progenitor cells (EPCs)
arising from the bone marrow, is likely to play an important role in the pathogenesis of
vessel loss in SSc.

This is a mechanistic study designed to address a key question—the role of vascular repair
in scleroderma vascular lesion formation following treatment in the SCOT study. Fifteen
subjects will be enrolled from each treatment arm of the SCOT trial, which is an
interventional, Phase II/III study for individuals with systemic sclerosis who are
randomized to receive either high dose immunosuppressive therapy (HDIT) followed by
autologous stem cell transplantation or monthly high dose intravenous cyclophosphamide (the
latter for 12 monthly cycles).

The study will evaluate the levels of EPCs in peripheral blood, the extent of vascular
damage and cell proliferation in cutaneous vasculature in subjects with SSc before and after
treatment, and the angiogenic activity in the skin grafts and the bone marrow response to
skin grafting in SCID mice using skin tissue obtained from SSc subjects pre-treatment and
approximately 12 months after the initiation of therapy.

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.

Inclusion Criteria:

- Participation in DAIT SCSSc-01 (SCOT Trial)

Exclusion Criteria:

- No additional exclusion criteria

We found this trial at

sites

City of Hope National Medical Center

1500 East Duarte Road
Duarte, California 91010

626-256-HOPE (4673)