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The purpose of the study is to assess skin blood flow after non-invasive local administration of treprostinil by using a low-intensity current (i.e. iontophoresis) on the forearm and the fingers of healthy volunteers and patients with systemic sclerosis. The investigators also aim at assessing the systemic bioavailability and dermal diffusion of treprostinil iontophoresis.
Digital ulcerations are a complication of systemic sclerosis (SSc). Available treatments (i.e. IV iloprost) induce major adverse effects, limiting the use of such therapies. Iontophoresis is a non invasive route of administration of drugs. In experimental and clinical preliminary studies, the investigators have shown that iontophoresis of treprostinil on the forearm of healthy subjects induces a sustained increase in skin blood flux and that it is well tolerated (clinicaltrials.gov NCT01082484, manuscript in press). The investigators therefore aim at validating this proof of concept on the digits of SSc patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cutaneous iontophoresis of Treprostenil | Experimental |
| |
| Cutaneous iontophoresis of placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cutaneous iontophoresis of treprostinil | Drug | Cutaneous iontophoresis of treprostinil 0.1mg/ml, on the forearm and the fingers. (charge 40-240 mC). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area under the curve (AUC) of cutaneous blood flow | Cutaneous blood flow assessed with Laser Speckle Contrast Imaging (LSCI) | 0, 15min, 30 min, 1h, 2h, 4h, 6h, 8h, 10h |
| Measure | Description | Time Frame |
|---|---|---|
| Treprostinil blood concentration | AUC of treprostinil concentration from the end of iontophoresis until 10 hours after iontophoresis | 0, 15min, 30 min, 1h, 2h, 4h, 6h, 8h, 10h |
| Treprostinil dermal concentration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jean-Luc Cracowski, MD | INSERM 003 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CIC pharmacology - University Hopsital of Grenoble | Grenoble | 38043 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 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. | |
| 16876881 | Background | Cracowski JL, Minson CT, Salvat-Melis M, Halliwill JR. Methodological issues in the assessment of skin microvascular endothelial function in humans. Trends Pharmacol Sci. 2006 Sep;27(9):503-8. doi: 10.1016/j.tips.2006.07.008. Epub 2006 Jul 31. |
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| ID | Term |
|---|---|
| D012595 | Scleroderma, Systemic |
| D045743 | Scleroderma, Diffuse |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012871 | Skin Diseases |
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AUC of treprostinil concentration in the dermis (collected with microdialysis) from the end of iontophoresis until 10 hours after iontophoresis
| 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h |
| 11092203 | Background | Herrick AL. Vascular function in systemic sclerosis. Curr Opin Rheumatol. 2000 Nov;12(6):527-33. doi: 10.1097/00002281-200011000-00009. |
| 15019750 | Background | Kalia YN, Naik A, Garrison J, Guy RH. Iontophoretic drug delivery. Adv Drug Deliv Rev. 2004 Mar 27;56(5):619-58. doi: 10.1016/j.addr.2003.10.026. |
| 18077494 | Background | Murray AK, Moore TL, King TA, Herrick AL. Vasodilator iontophoresis a possible new therapy for digital ischaemia in systemic sclerosis? Rheumatology (Oxford). 2008 Jan;47(1):76-9. doi: 10.1093/rheumatology/kem314. |
| 28387950 | Derived | Gaillard-Bigot F, Roustit M, Jourdil JF, Stanke-Labesque F, Cracowski JL. Vascular Effects of Treprostinil Cutaneous Iontophoresis on the Leg, Finger, and Foot. J Clin Pharmacol. 2017 Sep;57(9):1215-1220. doi: 10.1002/jcph.898. Epub 2017 Apr 7. No abstract available. |