Prostacyclin (PGI2) Pathway to Enhance Wound Healing in Diabetic Foot Ulcers (PGI2HEAL)

This is an interventional basic science trial for Diabetes Mellitus, Type 2 Read More

Inclusion criteria:

Groups 1,2,3,4:

• Informed consent signed
• Affiliated to social security insurance or beneficiary of social security insurance
• Aged of 18 or older

Group 1: healthy volunteers:

-Free from all acute and chronic pathology

Group 2: diabetic patients without DFU:

-Patients with type 2 diabetes according to the criteria of the American Diabetes Association (ADA), without DFU or history of DFU

Group 3: diabetic patients with DFU or recent history of DFU (occurred within the last two years):

-Patients with type 2 diabetes according to the criteria of the American Diabetes Association (ADA) with: One or more active grade 1A, 1C, 2A or 2C (University of Texas Classification of Diabetic Foot) foot ulcer of microvascular or mixed etiology; Or a recent history (<2 years) of foot ulcer of microvascular or mixed etiology.

Group 4 (to collect samples of foot skin biopsies to address secondary objectives ):

-Patients with type 2 diabetes according to the criteria of the American Diabetes Association (ADA),with neuropathy and DFU undergoing lower-limb surgery for skin ulcer (e.g. toe amputation).

Exclusion criteria

Groups 1, 2 and 3:

• 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.
• Presence of diabetic peripheral neuropathy above the ankle, defined as a scoring >3 of at least two of the four stimuli of the Neuropathy Disability Score (i.e. pinprick sensation, light touch, vibration, and temperature perception) (37).
• Infected wound, treated with antibiotics in the past 15 days.
• Critical ischemia of the lower limb, defined as leg pain at rest associated with ankle pressure <70 mmHg.
• History of hypersensitivity reaction to treprostinil, fluconazole, other azole compounds, L-NMMA, ketorolac, meloxicam, or any NSAIDs or acetylsalicylic acid, lidocaine (or any local anesthetic with an amide bond), or their excipients
• History of asthma, rhinitis, nasal polyps, angioedema, hives rash, or any other allergic reaction due to acetylsalicylic acid or any NSAID taking
• Pulmonary veno-occlusive disease (PVOD)
• Porphyria
• Hyperkalemia
• Active or uncontrolled cardiovascular disease as follows: Myocardial infarction, or angina within the previous 6 months; Severe ischemic heart disease; Arrhythmia (uncontrolled, symptomatic, requiring treatment or life-threatening); Congestive heart failure, or decompensated heart failure not medically controlled; Stroke or transient ischemic attack within the previous 3 months; Uncontrolled hypertension: systolic blood pressure (SBP)> 180 mmHg or diastolic blood pressure (DBP)> 105 mmHg (2 abnormal readings during visit) Valvular heart disease
• Severe liver disease (Child-Pugh C) at the time of enrollment
• Renal disease (creatinine >2 mg/dL and/or estimated glomerular filtration rate (GFR) <30 mL/min, history of dialysis)
• Active peptic ulcer disease, recent gastrointestinal bleeding or perforation, or history of peptic ulcer disease or gastrointestinal bleeding or perforation with NSAIDs
• Intracerebral or gastrointestinal hemorrhage, hemostasis disorder or every clinical status that may lead to bleeding
• Chronic venous disease defined as stage 4a and 4b of the Clinical-Etiological-Anatomical-Pathophysiological (CEAP) classification
• Cutaneous condition deemed incompatible with skin biopsy and dermal microdialysis by the investigator
• History of necrotic angiodermatitis
• Trauma or any clinical event susceptible to be responsible for hemorrhage within the previous 6 months
• Concomitant treatment with pentoxifylline, anticoagulants, probenecid, medicinal products known to prolong the QT interval or anti-inflammatory or analgesic dose of acetylsalicylic acid
• If concomitant treatment with NSAIDs, participants have to be stopped 1 week before the inclusion
• Pregnancy or Lactation
• Females with childbearing potential, defined as a premenopausal female capable of becoming pregnant, and not using an highly effective form of birth control. Effective birth control methods include: oral, implant or patch hormone contraception; intrauterine device; abstinence and outercourse; tubal ligation; vasectomy.

Groups 1,2,3 and 4:

• Participant involved in another interventional clinical study
• Person deprived of liberty by judicial order
• Person under guardianship or curatorship