Therapeutic Iontophoresis of Treprostinil in Systemic Sclerosis Digital UlcErations. A Proof of Concept Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Number of side-effects graduated according to NIH CTCAE 4.03
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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 in an exclusion period from another study,
- •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 in an exclusion period from another study,
- •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
研究组 & 干预措施
Treprostinil
the participant will receive 10 days of iontophoresis of treprostinil on a first site, each day the same site.
干预措施: Iontophoresis of treprostinil (Drug)
Placebo
the participant will receive 10 days of iontophoresis of NaCl on a second site, but the same time than treprostinil
干预措施: Iontophoresis of placebo (Drug)
结局指标
主要结局
Number of side-effects graduated according to NIH CTCAE 4.03
时间窗: 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 ".
次要结局
- 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)
- 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)