Clinical Trial: Treprostinil Iontophoresis in Systemic Sclerosis Digital UlcErations. A Proof of Concept Study

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Therapeutic Iontophoresis of Treprostinil in Systemic Sclerosis Digital UlcErations. A Proof of Concept Study

Brief Summary: The study is conducted to confirm the good tolerance of a continuous cathodal iontophoresis of the treprostinil hydrogel administered during 10 days on the pulp of the finger of healthy volunteer and on the ischemic digital ulcerations of Systemic Sclerosis patients, particularly to estimate the cutaneous tolerance of the procedure and the effect on the blood pressure.

Detailed Summary:

Systemic Sclerosis is a rare disease characterized by microvascular affection and cutaneous fibrosis. The digital ulcers are a severe and very invalidating complication. The vascular dysfunction is a key element in the pathogenesis of this disease, preceding the fibrosis. The physiopathology involves a vascular ischemia and mechanical factors or cutaneous calcinoses, or local trauma. The treatment of the digital ulcerations of the Systemic Sclerosis is at first preventive within the a good cutaneous and ungual hygiene, with recourse, as a preventive measure, to Bosentan, an endothelin antagonist. Iloprost by intravenous route is the recommended curative treatment, but patients present very frequent and dose - limiting side effects (headaches, vasomotor flushing, nausea, vomiting, maxillary pains, myalgia).

The paradox is that the decrease of the capillary density and the lower microvascular reactivity limits the distribution of the drug at its site of action when it is administered by intravenous route. High doses are then necessary to reach a sufficient concentration in the region of the wound, which generates side effects. The local administration of the drug could allow to by-pass this problem.

The investigator uses a technique for the topical administration of a vasodilator close to iloprost, treprostinil. This technique is iontophoresis. In the previous clinical trials INFLUX-IT and TIPPS, the investigator showed that the local cutaneous administration of treprostinil by cathodal iontophoresis at 0.03 milliAmper(mA)/cm2 is well tolerated (no local or systematic side effect in healthy volunteer, Systemic Sclerosis patients and diabetics). Iontophoresis induced a steady increase of the cutaneous blood flow of fingers. The investigator also showed that treprostinil was detectable in the dermis until 8 hours after the ion
Sponsor: University Hospital, Grenoble

Current Primary Outcome: Number of side-effects graduated according to NIH CTCAE 4.03 [ Time Frame: every day of iontophoresis from day 0 to day 9 ]

Side effects will be reported according to NIH CTCAE 4.03, particularly " Skin and subcutaneous tissue disorders " et " Vascular disorders ".


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Pharmacodynamical effect of iontophoresis of treprostinil hydrogel in healthy volunteers on pulp finger, leg and foot [ Time Frame: day 0 ]
    area under curve of the increase of the flow after the iontophoresis of the gel of treprostinil compared to the iontophoresis of Sodium Chloride (NaCl) measured by laser speckle imaging
  • Pharmacodynamical effect of 10 days of iontophoresis of treprostinil hydrogel in healthy volunteers and systemic sclerosis patients [ Time Frame: day 0 and day 9 ]
    cutaneous vascular conductance after the iontophoresis of the gel of treprostinil compared to the iontophoresis of NaCl measured by laser speckle imaging
  • Pharmacodynamical effect of 10 days of iontophoresis of treprostinil hydrogel in healthy volunteers and systemic sclerosis patients [ Time Frame: day 0 and day 9 ]
    Area under curve of the cutaneous flow after the iontophoresis of the gel of treprostinil compared to the iontophoresis of NaCl measured by laser speckle imaging
  • Effect of iontophoresis of treprostinil hydrogel on peri and intra ulcer flow [ Time Frame: day 0 and day 9 ]
    cutaneous vascular conductance of the ulceration areas after the iontophoresis of the gel of treprostinil compared to the iontophoresis of NaCl measured by laser speckle imaging
  • Systemic diffusion of the treprostinil hydrogel administered by iontophoresis [ Time Frame: day 0 and day 9 ]
    Plasmatic concentration of treprostinil


Original Secondary Outcome: Same as current

Information By: University Hospital, Grenoble

Dates:
Date Received: March 23, 2017
Date Started: April 2017
Date Completion: June 2019
Last Updated: April 13, 2017
Last Verified: March 2017