Clinical trial NCT01554540: Treprostinil Iontophoresis : a Pharmacodynamic and Pharmacokinetic Study
Official title: Pharmacodynamic and Pharmacokinetic Assessment of Treprostinil Iontophoresis on the Forearm and the Fingers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Scleroderma, Systemic
Keywords: Treprostinil
Scleroderma
Iontophoresis
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2012-03-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Cutaneous systemic scleroderma with sclerosed fingers

Exclusion Criteria:

* pregnant or breast-feeding women
* any chronic disease (in the control group)
* smoking

Primary outcomes:
measure: Area under the curve (AUC) of cutaneous blood flow
timeFrame: 0, 15min, 30 min, 1h, 2h, 4h, 6h, 8h, 10h
Secondary outcomes:
measure: Treprostinil blood concentration
timeFrame: 0, 15min, 30 min, 1h, 2h, 4h, 6h, 8h, 10h
measure: Treprostinil dermal concentration
timeFrame: 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h
Other outcomes:
Locations:
city: Grenoble
country: France
facility: CIC pharmacology - University Hopsital of Grenoble
Study officials:
affiliation: INSERM 003
name: Jean-Luc Cracowski, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: Herrick AL. Vascular function in systemic sclerosis. Curr Opin Rheumatol. 2000 Nov;12(6):527-33. doi: 10.1097/00002281-200011000-00009.
citation: 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.
citation: 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.
citation: 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.