Plerixafor in Diabetic Wound Healing

Diabetes Clinical Trial

— MOZOBL07740  

Official title:

Effect of a Single Plerixafor Injection on Diabetic Wound Healing. A Pilot, Double-blind, Placebo-controlled, Randomized Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02790957
• Other study ID #: 3694/Ao/15
• Status: Terminated
• Phase: Phase 2
• Start date: June 2016
• Est. completion date: November 2019

Study information

• Verified date: December 2019
• Source: University of Padova
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Chronic non-healing wounds represent a major source of morbidity, disability, and mortality in diabetic patients. Diabetes is the leading cause of non-traumatic limb amputations worldwide. Many patients with ischemic or neuroischemic wounds are not candidate to surgical/endovascular revascularization, owing to anatomical vascular reasons or for the underlying conditions and co-morbidities. Therefore, identification of novel medical treatment strategies to improve wound healing in diabetic patients is a major challenge for clinicians, researchers, and health care systems.

Defects in bone marrow (BM)-derive stem and progenitor cells, including EPCs (endothelial progenitor cells), contribute to diabetic complications. Stem cell mobilizing agents have been previously studied as an adjunctive therapy for critical limb ischemia and chronic non-healing wounds in diabetic and non-diabetic patients, as well as for the treatment of diabetic wound infections . Meta-analyses of such studies indicate that stem cell mobilization in these clinical conditions is safe and potentially effective in improving surrogate outcome measures and hard endpoints (such as rates of wound healing and amputation).

This study plans to evaluate whether a single injection of Plerixafor improves wound healing in diabetic patients with stage III-IV (neuro)ischemic wounds.

Description:

Chronic non-healing wounds represent a major source of morbidity, disability, and mortality in diabetic patients. Diabetes is the leading cause of non-traumatic limb amputations worldwide. Many patients with ischemic or neuroischemic wounds are not candidate to surgical/endovascular revascularization, owing to anatomical vascular reasons or for the underlying conditions and co-morbidities. Therefore, identification of novel medical treatment strategies to improve wound healing in diabetic patients is a major challenge for clinicians, researchers, and health care systems.

Defects in bone marrow (BM)-derive stem and progenitor cells, including EPCs, contribute to diabetic complications. Stem cell mobilizing agents have been previously studied as an adjunctive therapy for critical limb ischemia and chronic non-healing wounds in diabetic and non-diabetic patients, as well as for the treatment of diabetic wound infections . Meta-analyses of such studies indicate that stem cell mobilization in these clinical conditions is safe and potentially effective in improving surrogate outcome measures and hard endpoints (such as rates of wound healing and amputation).

However, diabetes impairs the response to the most commonly agent used to mobilize stem cells, namely human recombinant granulocyte colony stimulating factor (hrG-CSF). This notion comes from extensive data in animal models, a retrospective case series in patients with hematological disorders, a meta-analysis of studies conducted in patients with cardiovascular disease, and our proof-of-concept prospective study in otherwise healthy outpatients. Vice versa, our data strongly indicate that diabetic patients adequately mobilize stem/progenitor cells (including vascular progenitors, like EPCs) in response to the CXCR4 antagonist Plerixafor. Plerixafor (Mozobil, Sanofi) is clinically available in Europe (including Italy) as a second-line regimen for stem cell mobilization in patients with myeloma or lymphoma scheduled for autotransplantation, only in combination with hrG-CSF, after failure of hrG-CSF alone, to mobilize a sufficient amount of CD34+ stem cells to start apheresis. Preclinical studies in animal models of delayed and diabetic wound healing support the idea that Plerixafor can be effective as an adjunct therapy to accelerate diabetic wound healing.

This study plans to evaluate whether a single injection of Plerixafor improves wound healing in diabetic patients with stage III-IV (neuro)ischemic wounds.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: November 2019
• Est. primary completion date: August 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Type 1 or type 2 diabetes

• Men of 18-85 years or post-menopausal women <85 years of age

• Presence of neuroischemic or ischemic diabetic wound(s) of the leg(s) / foot(s) Texas grade 3 or 4, with or without infection.

• Ability to provide informed consent.

Exclusion Criteria:

• Sepsis

• Dialysis or severe chronic kidney disease (eGFR <20ml/min/1.73 mq)

• Advanced liver disease (defined as cirrhosis or transaminases >3 times ULN)

• Clinically relevant abnormalities in white blood cell counts at baseline.

• Hematologic disorders (lymphoma, myeloma, acute or chronic leukemia, chronic myeloproliferative disorders)

• Known or highly suspected solid cancer

• Women with childbearing potential

• Known hypersensitivity to Mozobil (Plerixafor or its components)

• Inability to provide informed consent

Related Conditions & MeSH terms

• Critical Limb Ischemia
• Diabetes
• Ischemia
• Wounds
• Wounds and Injuries

Intervention

Drug:
• Plerixafor
Single injection of 0.24 mg/kg Plerixafor
• Placebo
Single injection of an equal volume of NaCl solution

Locations

Country	Name	City	State
Italy	University Hospital of Padova	Padova

Sponsors (2)

Lead Sponsor	Collaborator
Gian Paolo Fadini	University Hospital Padova

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Wound healing rate	Comparison of wound healing rates in the 2 groups, defined as the complete healing of wounds after 6 months from randomization	6 months
Secondary	Wound size	Comparison of changes in wound size over time (up to 6 months) in the 2 groups.	6 months
Secondary	Oxygen tension	Comparison of changes in TcO2 (transcutaneous oxygen tension) over time (up to 6 months) in the 2 groups.	6 months
Secondary	Perfusion	Comparison of changes in ankle/brachial index over time (up to 6 months) in the 2 groups.	6 months
Secondary	Surgical intervention	Comparison of the rates of surgical intervention (including debridement and amputations) at 6 months in the 2 groups.	6 months
Secondary	Stem cell mobilization	Comparison of CD34+ cell mobilization (ratio of cell level at 6 hour post-Plerixafor administration and baseline) in patients with good versus poor outcomes	6 months
Secondary	Incidence of adverse events and reactions	Comparison in the incidence of adverse events and reactions in the 2 groups	6 months