Plerixafor in Diabetic Wound Healing

NCT ID: NCT02790957

Last Updated: 2019-12-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2019-11-30

Brief 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.

Detailed 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.

Conditions

Diabetes; Wounds; Critical Limb Ischemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Plerixafor

Single subcutaneous injection of Plerixafor (0.24 mg/kg)

Group Type: EXPERIMENTAL

Plerixafor

Intervention Type: DRUG

Single injection of 0.24 mg/kg Plerixafor

Placebo

Single injection of an equal volume of NaCl solution

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Single injection of an equal volume of NaCl solution

Interventions

Plerixafor

Single injection of 0.24 mg/kg Plerixafor

Intervention Type: DRUG

Placebo

Single injection of an equal volume of NaCl solution

Intervention Type: DRUG

Other Intervention Names

Mozobil

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Padova

OTHER

Sponsor Role: collaborator

Gian Paolo Fadini

OTHER

Sponsor Role: lead

Responsible Party

Gian Paolo Fadini

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Gian Paolo Fadini, MD PhD

Role: STUDY_CHAIR

University of Padova

Locations

University Hospital of Padova

Padua, , Italy

Countries

Italy

References

Albiero M, D'Anna M, Bonora BM, Zuccolotto G, Rosato A, Giorgio M, Iori E, Avogaro A, Fadini GP. Hematopoietic and Nonhematopoietic p66Shc Differentially Regulates Stem Cell Traffic and Vascular Response to Ischemia in Diabetes. Antioxid Redox Signal. 2022 Apr;36(10-12):593-607. doi: 10.1089/ars.2021.0097. Epub 2022 Jan 4.

Reference Type: DERIVED

PMID: 34538132 (View on PubMed)

Other Identifiers

3694/Ao/15

Identifier Type: -

Identifier Source: org_study_id