Enhancing wound healing in diabetic foot ulcers using the PGI2 pathway

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

This study is testing if a specific pathway can help improve wound healing in people with diabetic foot ulcers by looking at how blood flow affects healing.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital, Grenoble (other)
• Locations: 1 site (Grenoble)
• Trial ID: NCT05099367 on ClinicalTrials.gov

What this trial studies

This study investigates the role of the prostacyclin (PGI2) pathway in enhancing wound healing for patients with diabetic foot ulcers (DFUs). It compares three groups: healthy controls, diabetic patients without DFUs, and diabetic patients with DFUs. The study aims to understand the microcirculation's role in tissue survival and how PGI2 dysregulation contributes to microvascular dysfunction in diabetes. By analyzing skin biopsies and using microdialysis, the study seeks to uncover the mechanisms behind DFU complications and explore potential new treatments.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 or older with type 2 diabetes, either with or without diabetic foot ulcers.

Not a fit: Patients with acute or chronic pathologies unrelated to diabetes or those under 18 years old may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment options for diabetic foot ulcers, reducing complications and amputations.

How similar studies have performed: While there have been studies exploring microcirculation and diabetic ulcers, the specific focus on the PGI2 pathway in this context is relatively novel.

Eligibility criteria

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

Where this trial is running

Grenoble

• CHU Grenoble Alpes Centre d'investigation clinique — Grenoble, France (RECRUITING)

Study contacts

• Study coordinator: Alicia Guigui, pharmD,

Conditions: Diabetes Mellitus, Type 2, Diabetic Foot