Clinical Trial: Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: DISTOL-1: Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine: A Randomized, Double-blind, Placebo-controlled, Multicenter Study

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.

Detailed Summary:
Sponsor: United Therapeutics

Current Primary Outcome: Net Ulcer Burden [ Time Frame: Week 20 ]

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.


Original Primary Outcome: Reduction in net ulcer burden [ Time Frame: Baseline, Week 5, 10, 15 and 20 ]

Current Secondary Outcome:

  • Digital Ulcer Pain VAS [ Time Frame: Week 20 ]
    Digital ulcer pain was rated on a 100-mm VAS on which subjects were asked to rate their average overall hand pain during the last week. The recorded value was divided by 10, with values ranging from 0.0 (no pain) to 10.0 (unbearable pain), expressed to one decimal.
  • Patient Global Assessment of Digital Ulcer Severity VAS [ Time Frame: Week 20 ]

    Patients rated their global impression of digital ulcer severity on a 15-cm VAS from scaled 0 (no disease activity) to 100 (very severe disease).

    The term "severity" was used to measure the extent of disease activity and associated disability or discomfort the patient experienced during the indicated time period.

  • Physician Global Assessment of Digital Ulcer Severity VAS [ Time Frame: Week 20 ]

    Physicians rated their global impression of digital ulcer severity on a 15-cm VAS from scaled 0 (no disease activity) to 100 (very severe disease).

    The term "severity" was used to measure the extent of disease activity and associated disability or discomfort the patient experienced during the indicated time period.

  • Cochin Hand Function Scale (CHFS) [ Time Frame: Week 20 ]
    The CHFS has been demonstrated as a reliable and valid assessment of hand function at the activity level in persons with SSc. It is comprised of 18 questions with possible integer responses of 0 (without difficulty) to 5 (impossible). The CHFS Score is simply the sum of all 18 questions, divided by the number of questions actually answered, multiplied by 18. At least 10 of the 18 questions must have been answered in order for CHFS to be calculated. Therefore, CHFS Score values can range from 0 (least limitation) to 90 (most limitation). A higher score indicates more difficulty in hand function or greater disability.
  • Scleroderma Health Assessment Questionnaire (SHAQ) [ Time Frame: Week 20 ]
    The SHAQ is a patient self-administered instrument which has been previously validated in SSc and demonstrates meaningful clinical changes in the course of the disease over time. It is comprised of a 20 question instrument pertaining to specific activities with possible integer responses of 0 (without any difficulty) to 3 (unable to do), and five additional scleroderma-specific visual analog scale (VAS) domains (Overall Disease Activity, Raynaud's Phenomenon, Finger Ulcers, Breathing, and Intestinal Problems) with possible values ranging from 0.0 to 15.0. The 20 questions are divided into eight domains. A mean score is calculated for each domain ranging from 0 to 3. A composite HAQ DI score is calculated by dividing the summed domain scores by the number of domains answered. The composite score is reported, falling between 0 and 3 on an ordinal scale. The scores are interpreted as 0 (no impairment in function) to 3 (maximal impairment of function).
  • Modified Rodnan Skin Score (mRSS) [ Time Frame: Week 20 ]
    The skin thickening was assessed by the Investigator in 17 body areas: fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). Each area was scored 0-3; 0 representing normal skin and 3 being severe thickening. The mRSS was the sum of the individual skin assessment scores: possible range of 0-51; 0 (no thickening) to 51 (severe thickening in all 17 areas) .
  • Short-Form McGill Pain Questionnaire [ Time Frame: Week 20 ]
    The SF-MPQ assessment has three component scores: the pain rating index (PRI), a pain visual analogue numerical scale (Pain VAS) and the present pain intensity (PPI). PRI is calculated by summing the responses (0=None to 3=Severe) to the 15 questions describing pain during the previous week and rated on an intensity scale as 0= none, 1= mild, 2= moderate or 3= severe and has possible values ranging from 0 to 45. The Pain VAS is a 100 mm VAS on which subjects were asked to rate pain during the previous week with values ranging from no pain (0.0) to worst possible pain (10.0). The PPI rated pain on a 6-point category scale from 0 (no pain) to 5 (excruciating pain).
  • Patient Impression of Change (PIC) Questionnaire [ Time Frame: Week 20 ]
    The PIC questionnaire consisted of three Likert items that asked the subject to rate changes in their digital ulcer, Raynaud's phenomenon and disease status since their last visit on a seven-level scale (very much improved, much improved, somewhat improved, same, somewhat worse, much worse and very much worse).
  • Short Form 36 [ Time Frame: Week 20 ]
    Change in patient quality of life was measured by the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), a self-administered questionnaire covering eight areas: physical function, physical role, bodily pain, general health, vitality, social function, emotional role, and mental health. For each area, the score range from 0 (poorer

    Original Secondary Outcome:

    • Digital ulcer related pain as measured by Visual Analogue Scale (VAS) [ Time Frame: Baseline, Week 5, 10, 15 and 20 ]
    • Raynaud's Condition Score (RCS) [ Time Frame: weeks 5, 10, 15 and 20 ]
    • Short Form McGill Pain Questionnaire (SF-MPQ) [ Time Frame: Baseline, week 5, 10, 15 and 20 ]
    • Scleroderma Health Assessment Questionnaire (SHAQ) [ Time Frame: Baseline, week 5, 10, 15 and 20 ]
    • Cochin Hand Function Scale (CHFS) [ Time Frame: Baseline, week 5, 10, 15 and 20 ]
    • modified Rodnan Skin Score (mRSS) [ Time Frame: Baseline and week 20 ]
    • SF-36 [ Time Frame: Baseline, week 5, 10, 15, and 20 ]
    • patient and physician digital ulcer Visual Analogue Scales (VAS) [ Time Frame: Baseline, week 5, 10, 15 and 20 ]
    • serum biomarkers [ Time Frame: Baseline and week 20 ]
    • adverse events [ Time Frame: Throughout week 20 ]


    Information By: United Therapeutics

    Dates:
    Date Received: October 17, 2008
    Date Started: May 2009
    Date Completion:
    Last Updated: January 31, 2014
    Last Verified: January 2014