- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02530996
Systemic Sclerosis (SSc) Vasculopathy: Improved Clinical Monitoring and Treatment (Scleroderma)
April 1, 2021 updated by: VA Office of Research and Development
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
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 and third aim (which is reported in this PRS report) will examine if BH4 is effective in ameliorating vascular dysfunction in patients with SSc and 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.
Study Type
Interventional
Enrollment (Actual)
12
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Utah
-
Salt Lake City, Utah, United States, 84148
- VA Salt Lake City Health Care System, Salt Lake City, UT
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 95 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Diagnosis of systemic sclerosis (SSc, scleroderma) by ACR/EULAR 2013 criteria.
Exclusion Criteria:
- Age < 18
- Pregnant or breast feeding
- Unwillingness to consent
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Placebo before BH4
Six SSc received oral placebo 10 mg/kg and had flow mediated dilatation measured.
After a five day washout they crossed over to oral BH4 10 mg/kg and had flow mediated dilatation measured.
Blood samples were obtained from these SSc patients and assessed for oxidative stress.
|
BH4 10 mg/kg/day given once to a total of 12 SSc patients
Other Names:
Non-invasive technique, flow mediated dilatation (FMD) to define vasculopathy in SSc.
Other Names:
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.
Other Names:
|
Experimental: BH4 before Placebo
Six SSc received oral BH4 10 mg/kg and had flow mediated dilatation measured.
After a five day washout they crossed over to oral placebo 10 mg/kg and had flow mediated dilatation measured.
Blood samples were obtained from these SSc patients and assessed for oxidative stress.
|
BH4 10 mg/kg/day given once to a total of 12 SSc patients
Other Names:
Non-invasive technique, flow mediated dilatation (FMD) to define vasculopathy in SSc.
Other Names:
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Flow Mediated Dilatation (FMD)-Diameter of Artery
Time Frame: FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day washout period.
|
FMD diameter of artery (mm, higher better)
|
FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day washout period.
|
Flow Mediated Dilatation-shear Rate
Time Frame: FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day wash out period.
|
FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day wash out period.
|
|
Flow Mediated Dilatation- Blood Velocity
Time Frame: FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day wash out period.
|
FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day wash out period.
|
|
Flow Mediated Dilatation-blood Flow
Time Frame: FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day wash out period.
|
FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day wash out period.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Oxidative Stress Measurement-MDA: Malondialdehyde
Time Frame: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
MDA (lower better).
Plasma malondialdehyde assessed by Oxis Research/Percipio Bioscience, Foster City, CA.
|
Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
Oxidative Stress Measurement-catalase (CAT)
Time Frame: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
CAT (higher better) assessed by Cayman Chemical Company, Ann Arbor, MI.
|
Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
Oxidative Stress Measurement- Protein Carbonyl
Time Frame: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
Protein carbonyl (lower better).
Plasma protein carbonyl levels assessed by Northwest Life Science Specialties, LLC Vancouver, WA.
|
Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
Oxidative Stress Measurement- Ferric Reducing Ability of Plasma (FRAP)
Time Frame: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
FRAP (higher better).
FRAP assessed using the method described by Benzie and Strain.
|
Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
Oxidative Stress Measurement- Superoxide Dismutase (SOD)
Time Frame: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
SOD (higher better).
SOD assessed by Cayman Chemical Company, Ann Arbor, MI.
|
Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
Oxidative Stress Measurement- Interleukin 6 (IL-6)
Time Frame: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
IL-6 (lower better), assessed by R&D Systems, Minneapolis, MN.
|
Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
Oxidative Stress Measurement- Tumor Necrosis Factor Alpha (TNF-α,
Time Frame: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
TNF-α (lower better), assessed by R&D Systems, Minneapolis, MN.
|
Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
Oxidative Stress Measurement- C-reactive Protein (CRP)
Time Frame: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
CRP (lower better).
CRP assessed by R&D Systems, Minneapolis, MN.
|
Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Tracy M. Frech, MD MS, VA Salt Lake City Health Care System, Salt Lake City, UT
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 1, 2016
Primary Completion (Actual)
June 1, 2016
Study Completion (Actual)
December 31, 2019
Study Registration Dates
First Submitted
July 29, 2015
First Submitted That Met QC Criteria
August 19, 2015
First Posted (Estimate)
August 21, 2015
Study Record Updates
Last Update Posted (Actual)
April 5, 2021
Last Update Submitted That Met QC Criteria
April 1, 2021
Last Verified
April 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IMMA-006-14F
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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