Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Linksium | UNKNOWN |
| University Grenoble Alps | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
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 iontophoresis, without significant increase in the plasma. Thus, daily repeated iontophoresis on 10 days on ulcerated areas could allow to obtain therapeutic tissular concentrations.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treprostinil | Experimental | the participant will receive 10 days of iontophoresis of treprostinil on a first site, each day the same site. |
|
| Placebo | Placebo Comparator | the participant will receive 10 days of iontophoresis of NaCl on a second site, but the same time than treprostinil |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Iontophoresis of treprostinil | Drug | the participant will receive 10 days of iontophoresis of treprostinil on a first site |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of side-effects graduated according to NIH CTCAE 4.03 | Side effects will be reported according to NIH CTCAE 4.03, particularly " Skin and subcutaneous tissue disorders " et " Vascular disorders ". | every day of iontophoresis from day 0 to day 9 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacodynamical effect of iontophoresis of treprostinil hydrogel in healthy volunteers on pulp finger, leg and foot | 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 | day 0 |
Not provided
Inclusion Criteria:
Healthy Volunteers:
Systemic sclerosis patients:
Exclusion Criteria:
Healthy Volunteers
Systemic sclerosis patients:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jean-Luc CRACOWSKI, MD,PhD | CIC 1406 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Grenoble Alps University Hospital | Grenoble | 38043 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26833587 | Background | Gaillard-Bigot F, Roustit M, Blaise S, Cracowski C, Seinturier C, Imbert B, Carpentier P, Cracowski JL. Treprostinil Iontophoresis Improves Digital Blood Flow during Local Cooling in Systemic Sclerosis. Microcirculation. 2016 Apr;23(3):266-70. doi: 10.1111/micc.12272. | |
| 25843412 | Background | Hellmann M, Roustit M, Gaillard-Bigot F, Cracowski JL. Cutaneous iontophoresis of treprostinil, a prostacyclin analog, increases microvascular blood flux in diabetic malleolus area. Eur J Pharmacol. 2015 Jul 5;758:123-8. doi: 10.1016/j.ejphar.2015.03.066. Epub 2015 Apr 3. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D012595 | Scleroderma, Systemic |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012871 | Skin Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Iontophoresis of placebo | Drug | the participant will receive 10 days of iontophoresis of NaCl on a second site, but the same time than treprostinil; it's like a design of cross-over study |
|
| Pharmacodynamical effect of 10 days of iontophoresis of treprostinil hydrogel in systemic sclerosis patients |
cutaneous vascular conductance after the iontophoresis of the gel of treprostinil compared to the iontophoresis of NaCl measured by laser speckle imaging |
| day 0 and day 9 |
| Pharmacodynamical effect of 10 days of iontophoresis of treprostinil hydrogel in systemic sclerosis patients | 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 | day 0 and day 9 |
| Effect of iontophoresis of treprostinil hydrogel on peri and intra ulcer flow | 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 | day 0 and day 9 |
| Systemic diffusion of the treprostinil hydrogel administered by iontophoresis | Plasmatic concentration of treprostinil | day 0 and day 9 |
| 25712367 | Background | Kotzki S, Roustit M, Arnaud C, Godin-Ribuot D, Cracowski JL. Effect of continuous vs pulsed iontophoresis of treprostinil on skin blood flow. Eur J Pharm Sci. 2015 May 25;72:21-6. doi: 10.1016/j.ejps.2015.02.012. Epub 2015 Feb 21. |
| 24458011 | Background | Roustit M, Gaillard-Bigot F, Blaise S, Stanke-Labesque F, Cracowski C, Seinturier C, Jourdil JF, Imbert B, Carpentier PH, Cracowski JL. Cutaneous iontophoresis of treprostinil in systemic sclerosis: a proof-of-concept study. Clin Pharmacol Ther. 2014 Apr;95(4):439-45. doi: 10.1038/clpt.2013.255. Epub 2014 Jan 23. |
| 23838678 | Background | Kotzki S, Roustit M, Arnaud C, Boutonnat J, Blaise S, Godin-Ribuot D, Cracowski JL. Anodal iontophoresis of a soluble guanylate cyclase stimulator induces a sustained increase in skin blood flow in rats. J Pharmacol Exp Ther. 2013 Sep;346(3):424-31. doi: 10.1124/jpet.113.205484. Epub 2013 Jul 9. |
| 23400744 | Background | Blaise S, Roustit M, Hellmann M, Millet C, Cracowski JL. Cathodal iontophoresis of treprostinil induces a sustained increase in cutaneous blood flux in healthy volunteers. J Clin Pharmacol. 2013 Jan;53(1):58-66. doi: 10.1177/0091270011434352. Epub 2013 Jan 24. |
| 20860718 | Background | Blaise S, Roustit M, Millet C, Ribuot C, Boutonnat J, Cracowski JL. Cathodal iontophoresis of treprostinil and iloprost induces a sustained increase in cutaneous flux in rats. Br J Pharmacol. 2011 Feb;162(3):557-65. doi: 10.1111/j.1476-5381.2010.01045.x. |