Diabetic Foot UlcersPhase 3NCT02789033
Efficacy of the Combination of Isosorbide Dinitrate Spray and Chitosan in Diabetic Foot Ulcers
A Phase 3 study testing Chitosan and Isosorbide dinitrate in people with Diabetic Foot Ulcers, run by University of Guadalajara.
Trial summary
The prevalence of diabetic foot ulceration in the diabetic population is 4-10%; the condition is more frequent in elder patients. It is estimated that about 5% of all patients with diabetes present a history of foot ulceration, while the lifetime risk of diabetic patients developing this complication is 15%. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Diabetic Foot Ulcers
- What is being tested?
- Chitosan and Isosorbide dinitrate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- No sites listed yet
- Study dates
- Jun 2015to Aug 2015
- Phase
- Phase 3
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Patients with diabetic foot ulcers in grade I and II of the classification of Wagner
- with leg arm index> 0.8 and
- without specific treatment for foot ulcers referred to the experimental and clinical
Who cannot join
- Patients with another type of topical medication
- patients with diabetic foot ulcers in grade III and
- with leg arm index <0.8
About this study
The prevalence of diabetic foot ulceration in the diabetic population is 4-10%; the condition is more frequent in elder patients. It is estimated that about 5% of all patients with diabetes present a history of foot ulceration, while the lifetime risk of diabetic patients developing this complication is 15%. The majority (60-80%) of foot ulcers will heal, while 10-15% of them will remain active, and 5-24% of them will finally lead to limb amputation within a period of 6-18 months after the first evaluation , 2 out of 3 patients with a limb amputation could also be involved in a new amputation in the next year; higher or in the other leg , Eighty-five percent of lower-limb amputations in patients with diabetes are preceded by foot ulceration. The management of chronic diabetic foot ulcers (DFU) suggests multi-disciplinary approaches including control of diabetes, orthotic shoe wear, off-loading device, wound care and surgery in selected cases. However, treatment of DFU remains challenging because of unsatisfactory results from surgical and non-surgical treatments. Many adjunctive therapies are designed to improve the care of DFU including negative pressure wound therapy , ultrasound, recombinant human platelet-derived growth factor-BB (rPDGF-BB) Hyperbaric oxygen and acellular matrix product among others.
Read the detailed description
A randomized, placebo controlled, double-blind Clinical trial was designed. 60 Patients with diabetic foot ulcers in grade I and II of the classification of Wagner, with leg arm index> 0.8 and without specific treatment for foot ulcers referred to the experimental and clinical Therapeutic Institute will be included. All patients give written informed consent; previously the protocol was approved for the bioethics committee of the CUCS, of the Guadalajara University, registration number 030-2010. Patients with another type of topical medication will be excluded. Isosorbide dinitrate spray (2.5 mg).
Preparation of chitosan Hydrogels: The composition of gel formulation will be given prior training. ISDN and chitosan gel will be applied handled under aseptic conditions to the wound, and covered with sterile bandages. The patients will be evaluated every 2 weeks (macroscopic study and measurement of the ulcerated area) until 6 views. A second biopsy will be done one week before the finalization of the treatment of 15 weeks. The biopsies will be embedded on paraformaldehyde (4%) and paraffin. Sections of 5 µm were analyzed by a pathologist to determine hypertrophic and hyperplasic capillaries, inflammation and cellular matrix using Hematoxylin \& eosin and Masson's trichrome stains. An immunohistochemical stain was also realized to evaluate several molecular markers such as α-SMA (abcam, Cambridge, MA), Desmin (abcam, Cambridge, MA), VEGF (abcam, Cambridge, MA) and Von Willebrand Factor (Chemicon, CA). (figure 1) Statistical analysis: It will be done using SPSS program for Windows Version 10.0, the results of quantitative variables were expressed in average and standard deviation. The differences between baseline and subsequent pharmacologic intervention measurements will be investigated with the Wilcoxon test. The Mann Whitney U test will be used to compare groups. Frequencies by categories as well as percentages will be quantified for qualitative variables. Comparisons between groups were performed with Chi2. For all comparisons p < 0.05 will be considered as significant.
- Conditions
- Diabetic Foot Ulcers
- Being tested
- Chitosan, Isosorbide dinitrate, Placebo
- Keywords
- diabetic foot ulcers, chitosan, isosorbide dinitrate spray
- Medical subject headings
- Diabetic Foot
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChitosanDrug
Also called polymers
Chitosan chemically is a high-molecular-weight linear polycationic heteropolysaccharide comprising copolymers of 1,4-linked D-glucosamine and N-acetyl-D-glucosamine
Isosorbide dinitrateDrug
Also called organic nitrate
Isosorbide dinitrate (ISDN), is an organic nitrate, is a vasodilator with effects on both arteries and veins. The chemical name of ISDN is 1,4:3,6-dianhydro-D-glucitol 2,5-dinitrate
PlaceboDrug
Also called Magnessium Calcuim
placebo
| Study group | Role | What they receive |
|---|---|---|
| Chitosan | Active comparator | Chitosan chemically is a high-molecular-weight linear polycationic heteropolysaccharide comprising copolymers of 1,4-linked D-glucosamine and N-acetyl-D-glucosamine Receives: Drug: Chitosan; Drug: Isosorbide dinitrate |
| Isosorbide dinitrate spray | Active comparator | Isosorbide dinitrate spray (2.5 mg) is an organic nitrate, is a vasodilator with effects on both arteries and veins. The chemical name of ISDN is 1,4:3,6-dianhydro-D-glucitol 2,5-dinitrate. Receives: Drug: Chitosan; Drug: Isosorbide dinitrate |
| Placebo | Placebo comparator | Placebo in the same pharmacological presentation Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biopsies
Histological changes in ulcers
Measured: 75 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2016 (estimated)
- Study startJun 2015
- Primary completionAug 2015
- Study completionAug 2015
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 (11)Papers the sponsor has linked to this study.
- Other trials for Diabetic 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Guadalajara
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Leonel Garcia Benavides, University of Guadalajara
- Investigators
- Leonel Garcia, PhD, Principal investigator, University of Guadalajara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02789033
- Sponsor's protocol ID
- 030-2010
- Status last verified
- Dec 2020
- First submitted
- 24 Mar 2015
- Last updated
- 12 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Alexiadou K, Doupis J. Management of diabetic foot ulcers. Diabetes Ther. 2012 Nov;3(1):4. doi: 10.1007/s13300-012-0004-9. Epub 2012 Apr 20.
PubMed 22529027Reiber GE, Lipsky BA, Gibbons GW. The burden of diabetic foot ulcers. Am J Surg. 1998 Aug;176(2A Suppl):5S-10S. doi: 10.1016/s0002-9610(98)00181-0.
PubMed 9777967Xie X, McGregor M, Dendukuri N. The clinical effectiveness of negative pressure wound therapy: a systematic review. J Wound Care. 2010 Nov;19(11):490-5. doi: 10.12968/jowc.2010.19.11.79697.
PubMed 21135797Tiaka EK, Papanas N, Manolakis AC, Maltezos E. The role of hyperbaric oxygen in the treatment of diabetic foot ulcers. Angiology. 2012 May;63(4):302-14. doi: 10.1177/0003319711416804. Epub 2011 Aug 25.
PubMed 21873346Schaffer MR, Tantry U, Efron PA, Ahrendt GM, Thornton FJ, Barbul A. Diabetes-impaired healing and reduced wound nitric oxide synthesis: a possible pathophysiologic correlation. Surgery. 1997 May;121(5):513-9. doi: 10.1016/s0039-6060(97)90105-7.
PubMed 9142149Andrews KL, Irvine JC, Tare M, Apostolopoulos J, Favaloro JL, Triggle CR, Kemp-Harper BK. A role for nitroxyl (HNO) as an endothelium-derived relaxing and hyperpolarizing factor in resistance arteries. Br J Pharmacol. 2009 Jun;157(4):540-50. doi: 10.1111/j.1476-5381.2009.00150.x. Epub 2009 Mar 26.
PubMed 19338582Raafat D, von Bargen K, Haas A, Sahl HG. Insights into the mode of action of chitosan as an antibacterial compound. Appl Environ Microbiol. 2008 Jun;74(12):3764-73. doi: 10.1128/AEM.00453-08. Epub 2008 May 2.
PubMed 18456858Sezer AD, Cevher E, Hatipoglu F, Ogurtan Z, Bas AL, Akbuga J. Preparation of fucoidan-chitosan hydrogel and its application as burn healing accelerator on rabbits. Biol Pharm Bull. 2008 Dec;31(12):2326-33. doi: 10.1248/bpb.31.2326.
PubMed 19043221Girach A, Manner D, Porta M. Diabetic microvascular complications: can patients at risk be identified? A review. Int J Clin Pract. 2006 Nov;60(11):1471-83. doi: 10.1111/j.1742-1241.2006.01175.x.
PubMed 17073842Chabbert-Buffet N, LeDevehat C, Khodabandhelou T, Allaire E, Gaitz JP, Tribout L, Abdoucheli-Baudot N, Vayssairat M. Evidence for associated cutaneous microangiopathy in diabetic patients with neuropathic foot ulceration. Diabetes Care. 2003 Mar;26(3):960-1. doi: 10.2337/diacare.26.3.960. No abstract available.
PubMed 12610079Richards AM, Floyd DC, Terenghi G, McGrouther DA. Cellular changes in denervated tissue during wound healing in a rat model. Br J Dermatol. 1999 Jun;140(6):1093-9. doi: 10.1046/j.1365-2133.1999.02908.x.
PubMed 10354076
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of the Combination of Isosorbide Dinitrate Spray and Chitosan in Diabetic Foot Ulcers
- ClinicalTrials.gov ID
- NCT02789033
- Acronym / sponsor ID
- 030-2010
- Conditions
- Diabetic Foot Ulcers
- Keywords
- diabetic foot ulcers, chitosan, isosorbide dinitrate spray
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- University of GuadalajaraUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 2 Jun 2016 (estimated)
- Results
- Posted 12 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The prevalence of diabetic foot ulceration in the diabetic population is 4-10%; the condition is more frequent in elder patients. It is estimated that about 5% of all patients with diabetes present a history of foot ulceration, while the lifetime risk of diabetic patients developing this complication is 15%. The majority (60-80%) of foot ulcers will heal, while 10-15% of them will remain active, and 5-24% of them will finally lead to limb amputation within a period of 6-18 months after the first evaluation , 2 out of 3 patients with a limb amputation could also be involved in a new amputation in the next year; higher or in the other leg , Eighty-five percent of lower-limb amputations in patients with diabetes are preceded by foot ulceration. The management of chronic diabetic foot ulcers (DFU) suggests multi-disciplinary approaches including control of diabetes, orthotic shoe wear, off-loading device, wound care and surgery in selected cases. However, treatment of DFU remains challenging because of unsatisfactory results from surgical and non-surgical treatments. Many adjunctive therapies are designed to improve the care of DFU including negative pressure wound therapy , ultrasound, recombinant human platelet-derived growth factor-BB (rPDGF-BB) Hyperbaric oxygen and acellular matrix product among others.
Detailed description
A randomized, placebo controlled, double-blind Clinical trial was designed. 60 Patients with diabetic foot ulcers in grade I and II of the classification of Wagner, with leg arm index> 0.8 and without specific treatment for foot ulcers referred to the experimental and clinical Therapeutic Institute will be included. All patients give written informed consent; previously the protocol was approved for the bioethics committee of the CUCS, of the Guadalajara University, registration number 030-2010. Patients with another type of topical medication will be excluded. Isosorbide dinitrate spray (2.5 mg).
Preparation of chitosan Hydrogels: The composition of gel formulation will be given prior training. ISDN and chitosan gel will be applied handled under aseptic conditions to the wound, and covered with sterile bandages. The patients will be evaluated every 2 weeks (macroscopic study and measurement of the ulcerated area) until 6 views. A second biopsy will be done one week before the finalization of the treatment of 15 weeks. The biopsies will be embedded on paraformaldehyde (4%) and paraffin. Sections of 5 µm were analyzed by a pathologist to determine hypertrophic and hyperplasic capillaries, inflammation and cellular matrix using Hematoxylin \& eosin and Masson's trichrome stains. An immunohistochemical stain was also realized to evaluate several molecular markers such as α-SMA (abcam, Cambridge, MA), Desmin (abcam, Cambridge, MA), VEGF (abcam, Cambridge, MA) and Von Willebrand Factor (Chemicon, CA). (figure 1) Statistical analysis: It will be done using SPSS program for Windows Version 10.0, the results of quantitative variables were expressed in average and standard deviation. The differences between baseline and subsequent pharmacologic intervention measurements will be investigated with the Wilcoxon test. The Mann Whitney U test will be used to compare groups. Frequencies by categories as well as percentages will be quantified for qualitative variables. Comparisons between groups were performed with Chi2. For all comparisons p < 0.05 will be considered as significant.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Chitosan | Active comparator | Drug: Chitosan, Drug: Isosorbide dinitrateChitosan chemically is a high-molecular-weight linear polycationic heteropolysaccharide comprising copolymers of 1,4-linked D-glucosamine and N-acetyl-D-glucosamine |
| Isosorbide dinitrate spray | Active comparator | Drug: Chitosan, Drug: Isosorbide dinitrateIsosorbide dinitrate spray (2.5 mg) is an organic nitrate, is a vasodilator with effects on both arteries and veins. The chemical name of ISDN is 1,4:3,6-dianhydro-D-glucitol 2,5-dinitrate. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo in the same pharmacological presentation |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with diabetic foot ulcers in grade I and II of the classification of Wagner
- with leg arm index> 0.8 and
- without specific treatment for foot ulcers referred to the experimental and clinical
Key exclusion criteria (3 listed)
- Patients with another type of topical medication
- patients with diabetic foot ulcers in grade III and
- with leg arm index <0.8
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 |
|---|---|---|
| ChitosanAlso: polymersChitosan chemically is a high-molecular-weight linear polycationic heteropolysaccharide comprising copolymers of 1,4-linked D-glucosamine and N-acetyl-D-glucosamine | Drug | Chitosan, Isosorbide dinitrate spray |
| Isosorbide dinitrateAlso: organic nitrateIsosorbide dinitrate (ISDN), is an organic nitrate, is a vasodilator with effects on both arteries and veins. The chemical name of ISDN is 1,4:3,6-dianhydro-D-glucitol 2,5-dinitrate | Drug | Chitosan, Isosorbide dinitrate spray |
| PlaceboAlso: Magnessium Calcuimplacebo | Drug | Placebo |
Primary outcome
Biopsies
Time frame: 75 days
Histological changes in ulcers
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22529027Alexiadou K, Doupis J. Management of diabetic foot ulcers. Diabetes Ther. 2012 Nov;3(1):4. doi: 10.1007/s13300-012-0004-9. Epub 2012 Apr 20.
- Background: PubMed 9777967Reiber GE, Lipsky BA, Gibbons GW. The burden of diabetic foot ulcers. Am J Surg. 1998 Aug;176(2A Suppl):5S-10S. doi: 10.1016/s0002-9610(98)00181-0.
- Background: PubMed 21135797Xie X, McGregor M, Dendukuri N. The clinical effectiveness of negative pressure wound therapy: a systematic review. J Wound Care. 2010 Nov;19(11):490-5. doi: 10.12968/jowc.2010.19.11.79697.
- Background: PubMed 21873346Tiaka EK, Papanas N, Manolakis AC, Maltezos E. The role of hyperbaric oxygen in the treatment of diabetic foot ulcers. Angiology. 2012 May;63(4):302-14. doi: 10.1177/0003319711416804. Epub 2011 Aug 25.
- Background: PubMed 9142149Schaffer MR, Tantry U, Efron PA, Ahrendt GM, Thornton FJ, Barbul A. Diabetes-impaired healing and reduced wound nitric oxide synthesis: a possible pathophysiologic correlation. Surgery. 1997 May;121(5):513-9. doi: 10.1016/s0039-6060(97)90105-7.
- Background: PubMed 19338582Andrews KL, Irvine JC, Tare M, Apostolopoulos J, Favaloro JL, Triggle CR, Kemp-Harper BK. A role for nitroxyl (HNO) as an endothelium-derived relaxing and hyperpolarizing factor in resistance arteries. Br J Pharmacol. 2009 Jun;157(4):540-50. doi: 10.1111/j.1476-5381.2009.00150.x. Epub 2009 Mar 26.
- Background: PubMed 18456858Raafat D, von Bargen K, Haas A, Sahl HG. Insights into the mode of action of chitosan as an antibacterial compound. Appl Environ Microbiol. 2008 Jun;74(12):3764-73. doi: 10.1128/AEM.00453-08. Epub 2008 May 2.
- Background: PubMed 19043221Sezer AD, Cevher E, Hatipoglu F, Ogurtan Z, Bas AL, Akbuga J. Preparation of fucoidan-chitosan hydrogel and its application as burn healing accelerator on rabbits. Biol Pharm Bull. 2008 Dec;31(12):2326-33. doi: 10.1248/bpb.31.2326.
- Background: PubMed 17073842Girach A, Manner D, Porta M. Diabetic microvascular complications: can patients at risk be identified? A review. Int J Clin Pract. 2006 Nov;60(11):1471-83. doi: 10.1111/j.1742-1241.2006.01175.x.
- Background: PubMed 12610079Chabbert-Buffet N, LeDevehat C, Khodabandhelou T, Allaire E, Gaitz JP, Tribout L, Abdoucheli-Baudot N, Vayssairat M. Evidence for associated cutaneous microangiopathy in diabetic patients with neuropathic foot ulceration. Diabetes Care. 2003 Mar;26(3):960-1. doi: 10.2337/diacare.26.3.960. No abstract available.
- Background: PubMed 10354076Richards AM, Floyd DC, Terenghi G, McGrouther DA. Cellular changes in denervated tissue during wound healing in a rat model. Br J Dermatol. 1999 Jun;140(6):1093-9. doi: 10.1046/j.1365-2133.1999.02908.x.
- Individual participant dataSharing planned: No
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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.
Leonel Garcia, PhD principal investigator
University of Guadalajara
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Chitosan and Isosorbide dinitrate in people with Diabetic Foot Ulcers, run by University of Guadalajara.
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 3 inclusion and 3 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 12 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 12 Jan 2021). 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?
Biopsies (time frame: 75 days). 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 NCT02789033, which also lists 11 linked publications.
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 12 Jan 2021.