Iontophoresis of Treprostinil to Enhance Wound Healing in Diabetic Foot Skin Ulcers

38RC17.163

Assess the effect of iontophoresis of treprostinil on wound closure over 12 weeks, in patients with DFU. In the present study the investigators aim at establishing the proof-of-concept of iontophoresis of treprostinil as a potential treatment of diabetic foot ulcers in humans. The main hypothesis is that in patients with DFUs, the pharmacodynamic effect of a PGI2 analogue potentiates the effect of low-intensity current on microvascular function, tissue oxygenation and healing.

2020-01-28

2021-12-07

2021-12-07

Terminated

Early phase I

4

Inclusion Criteria: * Patients with type 2 diabetes according to the criteria of the American Diabetes Association (ADA), with one or more foot ulcer of microvascular or mixed etiology: * The ulcer size must be ≥1 cm² and \<20 cm² * Grade 1A, 1C, 2A or 2C (University of Texas Classification of Diabetic Foot) * Patient affiliated to social security insurance or beneficiary of social security insurance. Exclusion Criteria: * History of hypersensitivity reaction to treprostinil * Pulmonary veno-occlusive disease (PVOD) * Systemic treatment with any PGI2 analogue in the past two months. * Critical ischemia of the lower limb, defined as leg pain at rest associated with ankle pressure \<50 mmHg. * Infected wound, treated with antibiotics in the past 15 days. * Active or uncontrolled cardiovascular disease as follows: * Myocardial infarction, or angina within 6 months of study participation * Arrhythmia (uncontrolled, highly symptomatic, requires treatment or life-threatening). * Congestive heart failure. * Stroke or transient ischemic attack within 3 months of study participation * Uncontrolled hypertension: systolic blood pressure\> 180 mmHg or diastolic blood pressure\> 105 mmHg (2 abnormal readings during visit) * Valvular heart disease * Severe liver disease (Child-Pugh C) at the time of enrollment * Active gastroduodenal ulcer * Intracerebral hemorrhage * Trauma or any clinical event susceptible to be responsible for hemorrhage within 6 months of study participation * Renal disease (creatinine \> 2 mg/dL and/or estimated glomerular filtration rate\<30 mL/min, history of dialysis) * Unstable diabetes that has resulted in hyperosmolar coma or ketoacidosis, and/or documented increase or decrease in HbA1c of more than 2.0% within the previous 3 months. * Pregnancy or Lactation * Females of childbearing potential not using an effective form of birth control as determined by the investigators. * Participant involved in another interventional clinical study * Person deprived of liberty by judicial order * Person under guardianship or curatorship

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '2 sub-studies:\n\n* Preliminary safety study, Phase I: single ascending dose study that aims at establishing the safety, tolerability, and PK of the procedure in patients with active ulcers; we propose an accelerated titration design with 7 doses of gel. The accelerated phase (first four doses) uses single-patient cohorts per dose. After these doses, a standard 3+3 design will be performed. Any occurrence of dose-limiting toxicity (DLT) during the accelerated phase halts the accelerated titration and the cohort is expended to the standard 3+3 design. Two instances of DLT at a dose level halt escalation, and D-1 is the maximum tolerated dose.\n* Proof-of-concept study, Phase II: Thirty-six patients with DFU associated with microvascular dysfunction will be randomized into three groups: Treprostinil iontophoresis; Placebo iontophoresis; Standard care. Drug administration, but not standard care, will be double-blind. After a 10-day treatment, follow-up includes 6 visits over 10 weeks.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'TRIPLE', 'maskingDescription': 'Double blind (for the two groups treated with iontophoresis of treprostinil or placebo); open for the standard of care group.\n\nThe preparation of syringes of gel containing treprostinil or placebo will be centralized. Both gels will be physically identical, and investigators will not have access to the randomization list or to preparation records. This ensures proper blinding at treatment initiation. Treatment kits will subsequently be given to research nurses to continue the treatment at home. Nurses will not have access to the randomization list or preparation records either, which guarantees proper blinding throughout the 10-day treatment.\n\nUnblinding will be done in case of any suspicion of an unexpected serious adverse reaction, prior to the declaration of the event to the competent authorities. Unblinding may be done 24/24h by the Pharmacy department.', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 4, 'type': 'ACTUAL'}}

2023-12-12