Chronic Foot UlcersPhase 4NCT01472432
DPP IV Inhibition Facilitates Healing of Chronic Foot Ulcers in Type 2 Diabetes
A Phase 4 study testing vildagliptin in people with Chronic Foot Ulcers, run by University of Campania Luigi Vanvitelli at 1 site in Italy.
Trial summary
A randomized versus placebo trial designed to evaluate the clinical and humoral effects of 4 months of vildagliptin on healing of chronic ulcers in type 2 diabetes. Read more about this study
- Who is it for?
- Ages 40 to 70 years
- Conditions the study is for
- Chronic Foot Ulcers
- What is being tested?
- vildagliptin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 1 siteItaly
- Study dates
- May 2011to Jan 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 diabetes
- Oral hypoglycemic agents treatment
- Chronic foot ulcers
- Adequate blood circulation (perfusion) was assessed by a dorsum transcutaneous oxygen test >30 -mmHg, anklebrachial index values > 0.7 and < 1.2 with toe pressure > 30 mmHg, or Doppler arterial aveforms that were triphasic or biphasic at the ankle of the affected leg
- Written consensus
Who cannot join
- Active Charcot disease
- Ulcers resulting from electrical, chemical, or radiation burns
- Collagen vascular disease
- Ulcer malignancy
- Untreated osteomyelitis, or cellulitis
- Ulcer treatment with normothermic or hyperbaric oxygen therapy
Show all 11Show fewer
- Concomitant medications such as corticosteroids, immunosuppressive medications, or -chemotherapy
- Recombinant or autologous growth factor products
- Skin and dermal substitutes within 30 days of study start
- Use of any enzymatic debridement treatments
- Pregnant or nursing mothers
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dipeptidyl Peptidase (DPP) IV Inhibition Facilitates Healing of Chronic Foot Ulcers in Patients With Type 2 Diabetes
A randomized versus placebo trial designed to evaluate the clinical and humoral effects of 4 months of vildagliptin on healing of chronic ulcers in type 2 diabetes.
Read the detailed description
The chronic foot ulcer is a leading cause of hospital admissions for people with diabetes in the developed world and is a major morbidity associated with diabetes, often leading to pain, suffering, and a poor quality of life for patients. Chronic diabetic foot ulcers are estimated to occur in 15% of all patients with diabetes and precede 84% of all diabetes-related lower-leg amputations.The pathophysiology of chronic diabetic ulcers is complex and still incompletely understood, the most important predisposing factors being diabetic neuropathy and vasculopathy. Both micro and macroangiopathy strongly contribute to development and delayed healing of diabetic wounds, through an impaired tissue feeding and response to ischemia. HIF-1α and VEGF, as well as the NO production from iNOS, may contribute to limitation of hypoxic injury by promoting angiogenesis and wound healing. Experimental and pathological studies suggest that suggest that he incretin hormone glucagon-like peptide-1 (GLP-1) may improves VEGF generation, and promote pancreatic islet viability through the up-regulation of HIF1α.
Therefore, aim of this study is to evaluate the effect of the augmentation of GLP-1, by inhibitors of the dipeptidyl peptidase IV (DPP-4), such as vildagliptin, on HIF-1α, VEGF and iNOS in diabetic chronic ulcers.
- Conditions
- Chronic Foot Ulcers
- Being tested
- Placebo, vildagliptin
- Keywords
- type 2 diabetes, healing, foot ulcers, vildagliptin
- Medical subject headings
- Diabetes Mellitus, Type 2, Foot Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo is added to the standard good medical practice. Plus Metformin and/or Sulfonylurea
vildagliptinDrug
50 mg per os b.i.d. for 4 months of treatment, added to the standard good medical practice.Plus Metformin and/or Sulfonylurea
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | In the placebo group, the dose of other concomitant hypoglycemic medication was changed to obtain a similar profile of metabolic parameters. All patients had diabetes and at least one full-thickness wound below the ankle for >3 months. All patients were examined weekly for the first 4 weeks (day 28) then every other week until day 120 or ulcer closure by any means. At each visit, tracings of the wound margins were made for computer planimetry to document changes in wound size, and photographs were taken for a visual record. All patients followed the regular treatment at the multidisciplinary diabetes foot clinic, included treatment of infection, debridement, off-loading, and metabolic control according to high international standards and standard good medical practice. Receives: Drug: Placebo |
| Vildagliptin | Experimental | The experimental arm followed the same treatment of placebo group, but received also vildagliptin 50 mg per os b.i.d. for 4 months Receives: Drug: vildagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Full Epithelialization of the Wound
Biopsy is performed from the periphery of the ulcer, before and after treatment with vildagliptin, in order to evaluate the above referred outcome.
Optic microscopy is used to evaluate the epithelialization of the wound.
Measured: 3 months of treatment with vildagliptin
Capillary Density
Biopsy is performed from the periphery of the ulcer, before and after treatment with vildagliptin, in order to evaluate the above referred outcome.
Capillary density is measured using immunohistochemistry
Measured: 3 months of treatment with vildagliptin
Secondary outcomes (4)
HIF-1α
The factor is assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure are used to evaluate HIF-1α concentration. Higher values represent more factor.
Measured: 3 months
VEGF
The factor is assessed by immunoblot analysis (commercial kits).Arbitrary unit of measure are used to evaluate VEGF concentration. Higher values represent more factor.
Measured: 3 months
VEGF-R1 (Total and Phosphorylated Form), VEGF-R2 (Total and Phosphorylated Form)
The factor is assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure are used to evaluate VEGF-R1 concentration. Higher values represent more factor.
Measured: 3 months
iNOS
The factor is assessed by immunoblot analysis (commercial kits). Arbitrary unit of measure are used to evaluate iNOS concentration. Higher values represent more factor.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2011 (estimated)
- Study startMay 2011
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Foot UlcersStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Campania Luigi Vanvitelli
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Raffaele Marfella, University of Campania Luigi Vanvitelli
- Investigators
- Raffaele Marfella, MD, PhD, Principal investigator, Second University Naples
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01472432
- Sponsor's protocol ID
- IT 345461
- Status last verified
- Aug 2016
- First submitted
- 7 Nov 2011
- Last updated
- 11 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Marfella R, Sasso FC, Rizzo MR, Paolisso P, Barbieri M, Padovano V, Carbonara O, Gualdiero P, Petronella P, Ferraraccio F, Petrella A, Canonico R, Campitiello F, Della Corte A, Paolisso G, Canonico S. Dipeptidyl peptidase 4 inhibition may facilitate healing of chronic foot ulcers in patients with type 2 diabetes. Exp Diabetes Res. 2012;2012:892706. doi: 10.1155/2012/892706. Epub 2012 Nov 1.
PubMed 23197976
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dipeptidyl Peptidase (DPP) IV Inhibition Facilitates Healing of Chronic Foot Ulcers in Patients With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT01472432
- Acronym / sponsor ID
- IT 345461
- Conditions
- Chronic Foot Ulcers
- Keywords
- type 2 diabetes, healing, foot ulcers, vildagliptin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- University of Campania Luigi VanvitelliUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 16 Nov 2011 (estimated)
- Results
- Posted 4 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized versus placebo trial designed to evaluate the clinical and humoral effects of 4 months of vildagliptin on healing of chronic ulcers in type 2 diabetes.
Detailed description
The chronic foot ulcer is a leading cause of hospital admissions for people with diabetes in the developed world and is a major morbidity associated with diabetes, often leading to pain, suffering, and a poor quality of life for patients. Chronic diabetic foot ulcers are estimated to occur in 15% of all patients with diabetes and precede 84% of all diabetes-related lower-leg amputations.The pathophysiology of chronic diabetic ulcers is complex and still incompletely understood, the most important predisposing factors being diabetic neuropathy and vasculopathy. Both micro and macroangiopathy strongly contribute to development and delayed healing of diabetic wounds, through an impaired tissue feeding and response to ischemia. HIF-1α and VEGF, as well as the NO production from iNOS, may contribute to limitation of hypoxic injury by promoting angiogenesis and wound healing. Experimental and pathological studies suggest that suggest that he incretin hormone glucagon-like peptide-1 (GLP-1) may improves VEGF generation, and promote pancreatic islet viability through the up-regulation of HIF1α.
Therefore, aim of this study is to evaluate the effect of the augmentation of GLP-1, by inhibitors of the dipeptidyl peptidase IV (DPP-4), such as vildagliptin, on HIF-1α, VEGF and iNOS in diabetic chronic ulcers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboIn the placebo group, the dose of other concomitant hypoglycemic medication was changed to obtain a similar profile of metabolic parameters. All patients had diabetes and at least one full-thickness wound below the ankle for >3 months. All patients were examined weekly for the first 4 weeks (day 28) then every other week until day 120 or ulcer closure by any means. At each visit, tracings of the wound margins were made for computer planimetry to document changes in wound size, and photographs were taken for a visual record. All patients followed the regular treatment at the multidisciplinary diabetes foot clinic, included treatment of infection, debridement, off-loading, and metabolic control according to high international standards and standard good medical practice. |
| Vildagliptin | Experimental | Drug: vildagliptinThe experimental arm followed the same treatment of placebo group, but received also vildagliptin 50 mg per os b.i.d. for 4 months |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Type 2 diabetes
- Oral hypoglycemic agents treatment
- Chronic foot ulcers
- Adequate blood circulation (perfusion) was assessed by a dorsum transcutaneous oxygen test >30 -mmHg, anklebrachial index values > 0.7 and < 1.2 with toe pressure > 30 mmHg, or Doppler arterial aveforms that were triphasic or biphasic at the ankle of the affected leg
- Written consensus
Key exclusion criteria (11 listed)
- Active Charcot disease
- Ulcers resulting from electrical, chemical, or radiation burns
- Collagen vascular disease
- Ulcer malignancy
- Untreated osteomyelitis, or cellulitis
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 |
|---|---|---|
| PlaceboPlacebo is added to the standard good medical practice. Plus Metformin and/or Sulfonylurea | Drug | Placebo |
| vildagliptin50 mg per os b.i.d. for 4 months of treatment, added to the standard good medical practice.Plus Metformin and/or Sulfonylurea | Drug | Vildagliptin |
Primary outcome
Full Epithelialization of the Wound
Time frame: 3 months of treatment with vildagliptin
Biopsy is performed from the periphery of the ulcer, before and after treatment with vildagliptin, in order to evaluate the above referred outcome. Optic microscopy is used to evaluate the epithelialization of the wound.
Capillary Density
Time frame: 3 months of treatment with vildagliptin
Biopsy is performed from the periphery of the ulcer, before and after treatment with vildagliptin, in order to evaluate the above referred outcome. Capillary density is measured using immunohistochemistry
4 secondary outcomes
HIF-1α
Time frame: 3 months
VEGF
Time frame: 3 months
VEGF-R1 (Total and Phosphorylated Form), VEGF-R2 (Total and Phosphorylated Form)
Time frame: 3 months
iNOS
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23197976Marfella R, Sasso FC, Rizzo MR, Paolisso P, Barbieri M, Padovano V, Carbonara O, Gualdiero P, Petronella P, Ferraraccio F, Petrella A, Canonico R, Campitiello F, Della Corte A, Paolisso G, Canonico S. Dipeptidyl peptidase 4 inhibition may facilitate healing of chronic foot ulcers in patients with type 2 diabetes. Exp Diabetes Res. 2012;2012:892706. doi: 10.1155/2012/892706. Epub 2012 Nov 1.
- Individual participant dataSharing planned: Undecided
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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.
Raffaele Marfella, MD, PhD principal investigator
Second University Naples
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing vildagliptin in people with Chronic Foot Ulcers, run by University of Campania Luigi Vanvitelli 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 5 inclusion and 11 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: finished, as of the sponsor's last update on 11 Oct 2016. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Full Epithelialization of the Wound (time frame: 3 months of treatment with vildagliptin). The study lists 2 primary outcomes in all. 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 NCT01472432, 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 11 Oct 2016.