Systemic Sclerosis (SSc) Vasculopathy: Improved Clinical Monitoring and Treatment

Summary

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.

Conditions

• Rheumatologic Disease

Interventions

DRUG

BH4

BH4 10 mg/kg/day given once to a total of 12 SSc patients

DIAGNOSTIC_TEST

Vasculopathy assessment

Non-invasive technique, flow mediated dilatation (FMD) to define vasculopathy in SSc.

DRUG

Placebo

On the experimental days, patients reported to the laboratory after having consumed a standardized breakfast and oral BH4 (10mg/kg) or placebo five hours prior to their arrival. All measurements were taken at the same time of day to eliminate any diurnal effects. All participants abstained from alcohol, caffeine, and exercise for ≥12 hours prior to the study. Additionally, vasodilatory medications were discontinued 12 hours prior to study visit. In premenopausal women, measurements were performed during the early follicular phase of the menstrual cycle. All measurements were made under quiet, comfortable, ambient (\~22°C) laboratory conditions.

Sponsors & Collaborators

• VA Office of Research and Development

  lead FED

Principal Investigators

• Tracy M. Frech, MD MS · VA Salt Lake City Health Care System, Salt Lake City, UT

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

95 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2016-01-01

Primary Completion

2016-06-01

Completion

2019-12-31

FDA Drug

Yes

Countries

• United States

Study Locations