Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine
DISTOL-1
DISTOL-1: Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine: A Randomized, Double-blind, Placebo-controlled, Multicenter Study
1 other identifier
interventional
148
3 countries
30
Brief Summary
This study will evaluate the effect of treprostinil diethanolamine (UT-15C) sustained release tablets(compared to placebo) on digital ulcers in patients with scleroderma. Treprostinil diethanolamine is an analog of prostacyclin. Prostacyclin is a naturally occuring substance produced by the cells of blood vessels that inhibits platelet aggregation, induces vasodilation, and suppresses smooth muscle proliferation. Improvement in blood flow in lower limbs and fingers would be anticipated to result in a reduction in ischemic pain, Raynaud's phenomenon and promote healing of digital ulcers and other ischemic wounds.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2009
30 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 17, 2008
CompletedFirst Posted
Study publicly available on registry
October 20, 2008
CompletedStudy Start
First participant enrolled
May 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2011
CompletedResults Posted
Study results publicly available
March 17, 2014
CompletedDecember 28, 2023
December 1, 2023
1.8 years
October 17, 2008
January 31, 2014
December 7, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Net Ulcer Burden
Net ulcer burden was defined as the number of "new" or "active" digital ulcers (DU), plus the number of "indeterminate" DUs at that assessment that have previously been classified as either "active" or "new" at any earlier assessment during the study. A DU was defined as an area with visually discernable depth and a loss of continuity of epithelial coverage, which could be denuded or covered by a scab or necrotic tissue. If denuded, the DU was pronounced "active." If denudation could not be judged because of the presence of scab or necrotic tissue, DU presenting with features, including underlying pain, based on Investigator clinical judgment to be consistent with loss of epithelialization, epidermis, or dermis, and requiring treatment were designated as "active." Otherwise, the DU was pronounced "indeterminate." Only DUs distal to the proximal interphalangeal joints, volar to the equator of the finger, not localized in creases and vascular in origin were assessed.
Week 20
Secondary Outcomes (11)
Digital Ulcer Pain VAS
Week 20
Patient Global Assessment of Digital Ulcer Severity VAS
Week 20
Physician Global Assessment of Digital Ulcer Severity VAS
Week 20
Cochin Hand Function Scale (CHFS)
Week 20
Scleroderma Health Assessment Questionnaire (SHAQ)
Week 20
- +6 more secondary outcomes
Study Arms (2)
treprostinil diethanolamine
EXPERIMENTALTreprostinil diethanolamine sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
placebo (sugar pill)
PLACEBO COMPARATORMatching placebo sustained release tablet initiated at 0.25 mg BID and titrated up to a maximum dose of 16 mg BID or the individual's maximum tolerated dose.
Interventions
oral sustained release tablet. Maximum tolerable dose not exceeding 16 mg twice daily (BID)
Eligibility Criteria
You may qualify if:
- Subject gave voluntary written informed consent to participate in the study
- Diagnosis of systemic sclerosis (SSc) as defined by American College of Rheumatology (ACR) criteria
- Males and females age greater than 18 years at Screening
- Presence of at least one active digital ulcer (met protocol defined qualifications for active digital ulcer) at Baseline
- Females of childbearing potential willing to use a reliable form of medically acceptable contraception and have a negative pregnancy test at Screening and Baseline
- Able to communicate effectively with study personnel and willing to comply with protocol requirements
You may not qualify if:
- Diagnosis of pulmonary arterial hypertension (PAH)
- Body weight less than 40 kg at Screening and confirmed at Baseline
- History of postural hypotension, unexplained syncope, a blood pressure that is less than 90 mmHg systolic or 50 mmHg diastolic at Screening and Baseline
- Hemoglobin concentration less than 75% of the lower limit of the normal range at Screening
- Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C, or ALT greater than three times upper limit of normal
- Intractable diarrhea, or severe malabsorption, defined as greater than 15% unintentional loss of body weight in the last 6 months prior to Screening; any severe organ failure (e.g., lung, kidney), bleeding diathesis or platelet disorder, or any life-threatening condition
- Pregnant or breast-feeding
- Simultaneously fulfilled criteria for a second connective tissue disease including systemic lupus erythermatosus, rheumatoid arthritis or inflammatory myopathy
- Sympathectomy of the upper limb, involving the hand, performed within 12 months of Baseline. Sympathectomy performed on the non-target limb (hand not presenting with qualifying ulcers) or which did not include the hand, performed within 6 months of Baseline
- Receipt of prostanoid treatment (epoprostenol, treprostinil sodium, or other prostacyclin analog) within the previous 3 months of Baseline for conditions including Raynaud's phenomenon, rest pain and / or digital ulcers
- Required systemic antibiotics for infected digital ulcers within 2 weeks of Screening
- Local injection of botulinum toxin in an affected finger within 1 month prior to Baseline
- Treatment with endothelin receptor antagonists within 1 month prior to Baseline
- Patients on phosphodiasterase inhibitors, such as sildenafil or tadalafil, who have received treatment for less than 6 months prior to Baseline (unless for intermittent treatment of male erectile dysfunction)
- Treatment with statin within 1 month prior to Screening, unless for management of hyperlipidemia
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (30)
University of Alabama - Arthritis Clinical Intervention Program
Birmingham, Alabama, 35294, United States
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259, United States
UCLA
Los Angeles, California, 90095, United States
Stanford University School of Medicine/Palo Alto VA Health Care System
Palo Alto, California, 94304, United States
Denver Medical Center
Aurora, Colorado, 80045, United States
University of Connecticut Health Center
Farmington, Connecticut, 06030, United States
Georgetown University
Washington D.C., District of Columbia, 20007, United States
Northwestern University - Feinberg School of Medicine
Chicago, Illinois, 60611, United States
University of Indiana School of Medicine
Indianapolis, Indiana, 46202, United States
Johns Hopkins University - Division of Rheumatology
Baltimore, Maryland, 21224, United States
Boston University School of Medicine
Boston, Massachusetts, 02118, United States
University of Michigan Scleroderma Program
Ann Arbor, Michigan, 48106, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
UMDNJ Clinical Research Center
New Brunswick, New Jersey, 08903, United States
North Shore-LIJ Health System
Lake Success, New York, 11042, United States
The Hospital for Special Surgery
New York, New York, 10021, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
University of Toledo
Toledo, Ohio, 43614, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
University of Texas - Houston
Houston, Texas, 77030, United States
University of Utah
Salt Lake City, Utah, 84132, United States
Virginia Mason Medical Center
Seattle, Washington, 98111, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Dalhousie University - QEII Health Science Center
Halifax, Nova Scotia, B3H4K4, Canada
St Joseph's Health Care
London, Ontario, N6A4V2, Canada
McGill University
Montreal, Quebec, H3T1E2, Canada
Clinical Sciences Center - University Hospital
Liverpool, L9 7AL, United Kingdom
Royal Free Hospital - Center for Rheumatology
London, NW32QG, United Kingdom
Salford Royal Hospital
Manchester, M139PT, United Kingdom
Related Publications (1)
Mecoli CA, Perin J, Van Eyk JE, Zhu J, Fu Q, Allmon AG, Rao Y, Zeger S, Wigley FM, Hummers LK, Shah AA. Vascular biomarkers and digital ulcerations in systemic sclerosis: results from a randomized controlled trial of oral treprostinil (DISTOL-1). Clin Rheumatol. 2020 Apr;39(4):1199-1205. doi: 10.1007/s10067-019-04863-0. Epub 2019 Dec 19.
PMID: 31858338DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Oral Treprostinil Program Head
- Organization
- United Therapeutics Corporation
Study Officials
- PRINCIPAL INVESTIGATOR
James Seibold, MD
Scleroderma Research Consultants LLC, Avon, CT,
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 17, 2008
First Posted
October 20, 2008
Study Start
May 1, 2009
Primary Completion
March 1, 2011
Study Completion
July 1, 2011
Last Updated
December 28, 2023
Results First Posted
March 17, 2014
Record last verified: 2023-12