Systemic Sclerosis (SSc) Vasculopathy: Improved Clinical Monitoring and Treatment
| Status: | Recruiting |
|---|---|
| Conditions: | Cardiology, Neurology, Dermatology, Dermatology |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Dermatology / Plastic Surgery, Neurology |
| Healthy: | No |
| Age Range: | 18 - 95 |
| Updated: | 12/23/2018 |
| Start Date: | May 1, 2015 |
| End Date: | May 1, 2019 |
| Contact: | Martha Finco, MS |
| Email: | Martha.finco@va.gov |
| Phone: | (801) 585-6468 |
Systemic sclerosis (SSc; scleroderma) is a multi-organ systemic disease characterized by
activation of immune cells, which results in vascular dysfunction (vasculopathy) and
subsequent scarring (fibrosis). SSc has a higher than expect prevalence in the US military.
On a national level there are 5,766 SSc patients (ICD-9 710.1) presently cared for in the
Veterans Health Administration (VHA). While there is no cure for SSc, studies of therapeutics
that can help slow disease progression are valuable to our Veterans. This proposal addresses
the solicitation for projects with attention to SSc requested by President Obama after
reviewing potential contamination of water at Camp Lejeune. This proposal is a
patient-centered outreach for our Veterans with SSc to inform and prevent catastrophic
endstage vascular abnormalities, including digital ulcers, pulmonary arterial hypertension
(PAH) and scleroderma renal crisis in SSc. The study proposes a novel application of a
therapeutic for this disease. A better understanding of the initiating insult and natural
progression of SSc vasculopathy is needed in order to develop therapeutics with a goal of
curing/treating the underlying disease. This project has the potential to impact not only
Veterans with SSc, but also those with vascular abnormalities including digital ulcers, PAH,
and renal crisis. This proposal represents a potential major therapeutic advance for our
Veterans with SSc.
activation of immune cells, which results in vascular dysfunction (vasculopathy) and
subsequent scarring (fibrosis). SSc has a higher than expect prevalence in the US military.
On a national level there are 5,766 SSc patients (ICD-9 710.1) presently cared for in the
Veterans Health Administration (VHA). While there is no cure for SSc, studies of therapeutics
that can help slow disease progression are valuable to our Veterans. This proposal addresses
the solicitation for projects with attention to SSc requested by President Obama after
reviewing potential contamination of water at Camp Lejeune. This proposal is a
patient-centered outreach for our Veterans with SSc to inform and prevent catastrophic
endstage vascular abnormalities, including digital ulcers, pulmonary arterial hypertension
(PAH) and scleroderma renal crisis in SSc. The study proposes a novel application of a
therapeutic for this disease. A better understanding of the initiating insult and natural
progression of SSc vasculopathy is needed in order to develop therapeutics with a goal of
curing/treating the underlying disease. This project has the potential to impact not only
Veterans with SSc, but also those with vascular abnormalities including digital ulcers, PAH,
and renal crisis. This proposal represents a potential major therapeutic advance for our
Veterans with SSc.
Although SSc is heterogeneous in the extent of organ involvement and prognosis, it is
accepted that all SSc cases have a progressive and usually devastating course. Since
vasculopathy precedes fibrosis in this disease, a focus on understanding its natural history
and preventative measures for vascular dysfunction has profound implications. This pilot work
suggests that measurement of endothelial dysfunction with flow mediated dilatation (FMD)
holds promise as novel method to assess disease progression as well as the therapeutic
efficacy of the pharmacologic compound tetrahydrobiopterin (BH4) in SSc. The investigators
believe that BH4, which targets the endothelium, has great promise to reduce SSc-related
tissue hypoxia, end organ damage, and potentially may impact underlying disease progression.
The first aim will adopt an integrative approach and validate a novel, non-invasive
technique, FMD to define vasculopathy in SSc. The second aim will examine if BH4 is effective
in ameliorating vascular dysfunction in patients with SSc. The third aim will determine the
role of oxidative stress in BH4-mediated improvements in vascular function in patients with
SSc. The overarching goal of these aims is to improve vasculopathy detection and management
in Veterans with SSc.
accepted that all SSc cases have a progressive and usually devastating course. Since
vasculopathy precedes fibrosis in this disease, a focus on understanding its natural history
and preventative measures for vascular dysfunction has profound implications. This pilot work
suggests that measurement of endothelial dysfunction with flow mediated dilatation (FMD)
holds promise as novel method to assess disease progression as well as the therapeutic
efficacy of the pharmacologic compound tetrahydrobiopterin (BH4) in SSc. The investigators
believe that BH4, which targets the endothelium, has great promise to reduce SSc-related
tissue hypoxia, end organ damage, and potentially may impact underlying disease progression.
The first aim will adopt an integrative approach and validate a novel, non-invasive
technique, FMD to define vasculopathy in SSc. The second aim will examine if BH4 is effective
in ameliorating vascular dysfunction in patients with SSc. The third aim will determine the
role of oxidative stress in BH4-mediated improvements in vascular function in patients with
SSc. The overarching goal of these aims is to improve vasculopathy detection and management
in Veterans with SSc.
Inclusion Criteria:
- Diagnosis of systemic sclerosis (SSc, scleroderma) by ACR/EULAR 2013 criteria.
Exclusion Criteria:
- Age < 18
- Pregnant or breast feeding
- Unwillingness to consent
We found this trial at
1
site
Salt Lake City, Utah 84148
Principal Investigator: Tracy M. Frech, MD MS
Phone: 801-585-6468
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