Clinical trial NCT00775463: Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine
Official title: DISTOL-1: Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine: A Randomized, Double-blind, Placebo-controlled, Multicenter Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Sclerosis
Scleroderma
Keywords: Scleroderma, Diffuse
Scleroderma, Limited
Scleroderma, Systemic
Ulcer
prostacyclin
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2008-10-20
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Received an investigational product within 1 month preceding Screening
* Known hypersensitivity to treprostinil diethanolamine or any of the excipients
* Tobacco or nicotine use at any level within the past 6 months prior to Screening
* Any condition or laboratory that in the opinion of the investigator might interfere with subject's participation, pose an additional risk for the subject, could prevent understanding the objectives, nature or consequences of the trial, compliance with the protocol, adherence to therapy, or that would interfere with interpretation of study assessments

Primary outcomes:
measure: Net Ulcer Burden
timeFrame: Week 20
Secondary outcomes:
measure: Digital Ulcer Pain VAS
timeFrame: Week 20
measure: Patient Global Assessment of Digital Ulcer Severity VAS
timeFrame: Week 20
measure: Physician Global Assessment of Digital Ulcer Severity VAS
timeFrame: Week 20
measure: Cochin Hand Function Scale (CHFS)
timeFrame: Week 20
measure: Scleroderma Health Assessment Questionnaire (SHAQ)
timeFrame: Week 20
measure: Modified Rodnan Skin Score (mRSS)
timeFrame: Week 20
measure: Short-Form McGill Pain Questionnaire
timeFrame: Week 20
measure: Patient Impression of Change (PIC) Questionnaire
timeFrame: Week 20
measure: Short Form 36
timeFrame: Week 20
measure: Time to Ulcer Healing- Percentage of Subjects With Complete Healing
timeFrame: Week 20
measure: Time to Ulcer Healing
timeFrame: Week 20
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Arthritis Clinical Intervention Program
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine/Palo Alto VA Health Care System
state: California
city: Aurora
country: United States
facility: Denver Medical Center
state: Colorado
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Chicago
country: United States
facility: Northwestern University - Feinberg School of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: University of Indiana School of Medicine
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University - Division of Rheumatology
state: Maryland
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Scleroderma Program
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New Brunswick
country: United States
facility: UMDNJ Clinical Research Center
state: New Jersey
city: Lake Success
country: United States
facility: North Shore-LIJ Health System
state: New York
city: New York
country: United States
facility: The Hospital for Special Surgery
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: University of Texas - Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Halifax
country: Canada
facility: Dalhousie University - QEII Health Science Center
state: Nova Scotia
city: London
country: Canada
facility: St Joseph's Health Care
state: Ontario
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Liverpool
country: United Kingdom
facility: Clinical Sciences Center - University Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital - Center for Rheumatology
city: Manchester
country: United Kingdom
facility: Salford Royal Hospital
Study officials:
affiliation: Scleroderma Research Consultants LLC, Avon, CT,
name: James Seibold, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.