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

NCT03120533 | Completed Phase 1 DMC

• 1 other identifier: 38RC16.005
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Scleroderma, Systemic

Keywords

iontophoresis; treprostinil

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Pharmacodynamical effect of iontophoresis of treprostinil hydrogel in healthy volunteers on pulp finger, leg and foot

  day 0

• Pharmacodynamical effect of 10 days of iontophoresis of treprostinil hydrogel in systemic sclerosis patients

  day 0 and day 9

• Pharmacodynamical effect of 10 days of iontophoresis of treprostinil hydrogel in systemic sclerosis patients

  day 0 and day 9

• Effect of iontophoresis of treprostinil hydrogel on peri and intra ulcer flow

  day 0 and day 9

• Systemic diffusion of the treprostinil hydrogel administered by iontophoresis

  day 0 and day 9

Study Arms (2)

Treprostinil

EXPERIMENTAL

the participant will receive 10 days of iontophoresis of treprostinil on a first site, each day the same site.

Drug: Iontophoresis of treprostinil

Placebo

PLACEBO COMPARATOR

the participant will receive 10 days of iontophoresis of NaCl on a second site, but the same time than treprostinil

Drug: Iontophoresis of placebo

Interventions

Iontophoresis of treprostinil DRUG

the participant will receive 10 days of iontophoresis of treprostinil on a first site

Treprostinil

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy Volunteers:
• Age of at least 18 years
• Existence of a contraceptive method for women of child-bearing age
• Person affiliated to social security or beneficiary of such a scheme
• Signed consent form
• Systemic sclerosis patients:
• Systemic sclerosis meeting the EULAR criteria.
• Presence of 1 ischemic digital cutaneous ulceration , with digital ulcer classified as "active ulcers" according to the North American working group definition: epithelial denudation is clearly Visible at one place and the bed of de-epithelialized ulcer can be seen; Ulcerations distal to the proximal interphalangeal joint, not associated with calcinosis or bony relief.
• Ulcers whose major axis measured with the electronic caliper is ≥ 2 mm
• Age greater than or equal to 18 years
• Existence of a contraceptive method for women of reproductive age
• A person who is or is a beneficiary of social security
• Informed and signed consent signed by the patient or his / her legal representative.

You may not qualify if:

• Healthy Volunteers
• Treprostinil contraindications: Known hypersensitivity to treprostinil or any of the excipients, Pulmonary arterial hypertension related to veno-occlusive disease, Congestive heart failure due to severe left ventricular dysfunction, Severe hepatic insufficiency (Child-Pugh stage C), Evolving gastrointestinal ulcer, intracranial hemorrhage, recent trauma or other clinical condition that may lead to bleeding, Congenital or acquired valvular abnormalities with cardiac repercussions, Severe ischemic heart disease or unstable angina; Myocardial infarction in the last six months; Decompensated cardiac insufficiency not medically controlled; Severe arrhythmias; Cerebrovascular lesions (such as transient ischemic attack, stroke) that occurred within the last three months.
• Persons referred to in Articles L1121-5 to L1121-8 of the French Public health Code: pregnant woman, parturient, nursing mother, person deprived of liberty by judicial or administrative decision, person subject to a legal protection measure, can not Be included in clinical trials.
• Subject who would receive more than 4500 euros of compensation due to his participation in other biomedical research in the 12 months preceding this study
• Systemic sclerosis patients:
• Iloprost cure carried out in the previous month or planned in the following month.
• Initiation or change of dosage of bosentan, sildenafil or calcium channel blockers in the previous month or in the following month
• Digital Sympathectomy or botulinum toxin injection planned in the following month.
• Clinically superinfected digital ulcers
• Treprostinil contraindications: Known hypersensitivity to treprostinil or any of the excipients, Pulmonary arterial hypertension related to veno-occlusive disease, Congestive heart failure due to severe left ventricular dysfunction, Severe hepatic insufficiency (Child-Pugh stage C), Evolving gastrointestinal ulcer, intracranial hemorrhage, recent trauma or other clinical condition that may lead to bleeding, Congenital or acquired valvular abnormalities with cardiac repercussions, Severe ischemic heart disease or unstable angina; Myocardial infarction in the last six months; Decompensated cardiac insufficiency not medically controlled; Severe arrhythmias; Cerebrovascular lesions (such as transient ischemic attack, stroke) that occurred within the last three months.
• Persons referred to in Articles L1121-5 to L1121-8 of the French Public health Code: pregnant woman, parturient, nursing mother, person deprived of liberty by judicial or administrative decision, person subject to a legal protection measure, can not Be included in clinical trials.
• Subject who would receive more than 4500 euros of compensation due to his participation in other biomedical research in the 12 months preceding this study

Sponsors & Collaborators

• University Hospital, Grenoble: lead
• Linksium: collaborator
• University Grenoble Alps: collaborator

Study Sites (1)

Grenoble Alps University Hospital

Grenoble, 38043, France

Location

Related Publications (7)

• 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.

  PMID: 26833587 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.

  PMID: 25843412 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.

  PMID: 25712367 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.

  PMID: 24458011 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.

  PMID: 23838678 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.

  PMID: 23400744 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.

  PMID: 20860718 BACKGROUND

MeSH Terms

Conditions

Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Jean-Luc CRACOWSKI, MD,PhD

  CIC 1406

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2017
• First Posted: April 19, 2017
• Study Start: June 20, 2017
• Primary Completion: June 3, 2019
• Study Completion: June 3, 2019
• Last Updated: April 10, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)