DiabetesPhase 2MOZOBL07740NCT02790957
Plerixafor in Diabetic Wound Healing
A Phase 2 study testing Plerixafor in people with Diabetes and Wounds, run by Gian Paolo Fadini at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Diabetes, Wounds, Critical Limb Ischemia
- What is being tested?
- Plerixafor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2016to Nov 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- Women with childbearing potential
- Known hypersensitivity to Mozobil (Plerixafor or its components)
- Inability to provide informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of a Single Plerixafor Injection on Diabetic Wound Healing. A Pilot, Double-blind, Placebo-controlled, Randomized Trial
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.
Read the 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
- Being tested
- Plerixafor, Placebo
- Medical subject headings
- Diabetes Mellitus, Wounds and Injuries, Chronic Limb-Threatening Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlerixaforDrug
Also called Mozobil
Single injection of 0.24 mg/kg Plerixafor
PlaceboDrug
Single injection of an equal volume of NaCl solution
| Study group | Role | What they receive |
|---|---|---|
| Plerixafor | Experimental | Single subcutaneous injection of Plerixafor (0.24 mg/kg) Receives: Drug: Plerixafor |
| Placebo | Placebo comparator | Single injection of an equal volume of NaCl solution Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Wound healing rate
Comparison of wound healing rates in the 2 groups, defined as the complete healing of wounds after 6 months from randomization
Measured: 6 months
Secondary outcomes (6)
Wound size
Comparison of changes in wound size over time (up to 6 months) in the 2 groups.
Measured: 6 months
Oxygen tension
Comparison of changes in TcO2 (transcutaneous oxygen tension) over time (up to 6 months) in the 2 groups.
Measured: 6 months
Perfusion
Comparison of changes in ankle/brachial index over time (up to 6 months) in the 2 groups.
Measured: 6 months
Surgical intervention
Comparison of the rates of surgical intervention (including debridement and amputations) at 6 months in the 2 groups.
Measured: 6 months
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
Measured: 6 months
Incidence of adverse events and reactions
Comparison in the incidence of adverse events and reactions in the 2 groups
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2016 (estimated)
- Study startJun 2016
- Primary completionAug 2019
- Study completionNov 2019
Why it stopped: Safety reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gian Paolo Fadini
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Padova
- Responsible party
- Sponsor-investigator, Gian Paolo Fadini, University of Padova
- Investigators
- Gian Paolo Fadini, MD PhD, Study chair, University of Padova
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02790957
- Sponsor's protocol ID
- 3694/Ao/15
- Acronym
- MOZOBL07740
- Status last verified
- Dec 2019
- First submitted
- 31 May 2016
- Last updated
- 19 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 34538132
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of a Single Plerixafor Injection on Diabetic Wound Healing. A Pilot, Double-blind, Placebo-controlled, Randomized Trial
- ClinicalTrials.gov ID
- NCT02790957
- Acronym / sponsor ID
- MOZOBL07740 / 3694/Ao/15
- Conditions
- Diabetes, Wounds, Critical Limb Ischemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Safety reasons
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Gian Paolo FadiniUniversity, hospital or other
- Collaborators
- University Hospital Padova
- Study start
- Jun 2016 (actual)
- Primary completion
- Aug 2019 (actual)
- Study completion
- Nov 2019 (actual)
- First posted
- 6 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Plerixafor | Experimental | Drug: PlerixaforSingle subcutaneous injection of Plerixafor (0.24 mg/kg) |
| Placebo | Placebo comparator | Drug: PlaceboSingle injection of an equal volume of NaCl solution |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlerixaforAlso: MozobilSingle injection of 0.24 mg/kg Plerixafor | Drug | Plerixafor |
| PlaceboSingle injection of an equal volume of NaCl solution | Drug | Placebo |
Primary outcome
Wound healing rate
Time frame: 6 months
Comparison of wound healing rates in the 2 groups, defined as the complete healing of wounds after 6 months from randomization
6 secondary outcomes
Wound size
Time frame: 6 months
Oxygen tension
Time frame: 6 months
Perfusion
Time frame: 6 months
Surgical intervention
Time frame: 6 months
Stem cell mobilization
Time frame: 6 months
Incidence of adverse events and reactions
Time frame: 6 months
Results and safety
The study was stopped early (reason given: Safety reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2019.
- Derived from this study: PubMed 34538132Albiero 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gian Paolo Fadini, MD PhD study chair
University of Padova
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Plerixafor in people with Diabetes and Wounds, run by Gian Paolo Fadini at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Safety reasons). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Wound healing rate (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02790957, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2019.