Iontophoresis of Treprostinil to Enhance Wound Healing in Diabetic Foot Skin Ulcers (InTREPiD)
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|ClinicalTrials.gov Identifier: NCT03654989|
Recruitment Status : Recruiting
First Posted : August 31, 2018
Last Update Posted : January 18, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Diabetic Foot Ulcer||Drug: Treprostinil iontophoresis Device: Remodulin® placebo iontophoresis||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||
|Masking:||Triple (Participant, Care Provider, Outcomes Assessor)|
Double blind (for the two groups treated with iontophoresis of treprostinil or placebo); open for the standard of care group.
The 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.
Unblinding 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.
|Official Title:||Iontophoresis of Treprostinil to Enhance Wound Healing in Diabetic Foot Skin Ulcers|
|Estimated Study Start Date :||May 2020|
|Estimated Primary Completion Date :||July 2020|
|Estimated Study Completion Date :||September 2023|
Experimental: Treprostinil iontophoresis
Gel of treprostinil 1 mg/mL (target concentration)
Drug: Treprostinil iontophoresis
We will administer treprostinil at increasing doses by a iontophoresis.
Placebo Comparator: Remodulin® Placebo iontophoresis
Placebo will be made from the placebo of Remodulin® incorporated into hydrogel (Suprasorb® G). The route and frequency of administration will be the same as for the investigational drug (topical administration by iontophoresis).
Device: Remodulin® placebo iontophoresis
Placebo iontophoresis will be performed using Remodulin® placebo (United Therapeutics) delivered with Axion GmbH electrodes connected to a PeriIont generator (Perimed).
No Intervention: Standard care
subjects randomized to the standard of care group (no iontophoresis) will only undergo standard blood test at visit 0 or 1, unless tests <1 month before inclusion are available This group is not double blind Standard care consists on debridement and dressings
- Comparison of wound closure between the 3 groups: iontophoresis of treprostinil, iontophoresis of placebo, and standard of care, over12 weeks. [ Time Frame: Up to 12 weeks ]Wound closure is expressed as the percentage change non-reepithelialized skin area over time (12-week follow-up), assessed with a digital camera and image analysis software.
- The percentage of patients with complete healing at the last follow-up visit [ Time Frame: week 12 ]Wound area will be assessed with a digital camera and image analysis software.
- Comparison of time to complete healing between groups [ Time Frame: From date of randomization until the date of documented healing, assessed up to 12 months. ]Time to complete reepithelialization will be sought in the medical record on a monthly basis.
- The effect of iontophoresis of treprostinil on skin perfusion assessed with laser speckle contrast imaging at the site of the ulcer and around the wound [ Time Frame: day 9 ]Cutaneous perfusion will be assessed as cutaneous vascular conductance, and compared between groups
- Comparison of skin oxygenation around the lesion and on healed skin (when possible) [ Time Frame: Day 0 and Day 9 and week 12 ]Comparison using transcutaneous pressure of oxygen
- 8-hour PK profile. AUC0-8 [ Time Frame: part 1 : V1 (day0) V2 (day3 or more after V1) V3 (day3 or more after V2) V4 (day3 or more after V3), Part 2 : at days 0 and 9 ]8-hour PK profile. AUC0-8 will be calculated from seven time points: immediately after the end of iontophoresis ( T0), 15 min, 30 min, 1h, 2h, 4h, and 8h
- Incidence of treatment-emergent adverse events, among which hypotension, any cutaneous reaction at the site of iontophoresis, local pain, liver enzymes. [ Time Frame: During all the study, 3 months of follow-up for every subject ]All adverse events will be rated according to the NIH Common Terminology Criteria for Adverse Events.
- Evaluation of safety via blood pressure [ Time Frame: During all the study, 3 months of following for every subject ]Blood pressure will be continuously recorded with digital photoplethysmography.
- Evaluation of safety via the appearance of the wound [ Time Frame: During all the study, 3 months of following for every subject ]Photographs of the wound will be taken and sent to investigators, blinded to the group
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03654989
|Contact: Matthieu Roustit, PharmD, PhD||+33-476-769-260||MRoustit@chu-grenoble.fr|
|Contact: Adeline Paris, pharmacist||+33-476-767-383||Aparis@chu-grenoble.fr|
|CHU Grenoble Alpes||Recruiting|
|Contact: Jean-Luc CRACOWSKI, Pr|
|Principal Investigator:||Cracowski Jean-luc, Professor||Clinical pharmacology unit, grenoble alpes university hospital|