Effect of Deferoxamine on Wound Healing Rate in Patients With Diabetes Foot Ulcers

NCT03137966 | Not Yet Recruiting Phase 2

• 1 other identifier: 170428-DEFEHU
• Study Type: interventional
• Target: 174
• Locations: 0 countries
• Sites: N/A

Brief Summary

Diabetic foot ulcer (DFU) is one of the most invalidating complication of diabetes and represents a big economic burden for the society. No specific therapy is available for diabetic foot ulcers.The aim of this study is to define a new approach for treatment of chronic diabetic wounds. Our concept is based on the improvement of the cellular reaction to hypoxia. It will address the transcriptional factor HIF-1 (Hypoxia inducible factor-1) which is the cellular sensor for oxygen and which is specifically repressed by hyperglycemia. The study will investigate the effect of local deferoxamine (0.66 mg/ml), the only known HIF-1 inducer, on the wound healing rate in patients with neuropathic diabetic foot ulcers. The primary objective of the study will be the reduction with \>50% of the wound area after 12 weeks of treatment.

Conditions

Diabetic Foot Ulcer

Keywords

Diabetes mellitus, foot ulcer, deferoxamine

Outcome Measures

Primary Outcomes (1)

• Healing

  number of patients who have intact skin healing

  3 months

Secondary Outcomes (1)

• Improvement of ulcer

  3 months

Study Arms (2)

Deferoxamine

ACTIVE COMPARATOR

Patients will be randomised to treatment with Deferoxamine (n=87). Deferoxamine (0.66mg/ml) will be applied locally as a gel (3 times a week) for a period of maximum three months or until intact skin.

Drug: Deferoxamine

Placebo

PLACEBO COMPARATOR

Patients will be randomised to treatment with placebo (n=87). Placebo will be applied locally as a gel (3 times a week) for a period of maximum three months or until intact skin.

Drug: Placebo

Interventions

Deferoxamine DRUG

Deferoxamine (0.66mg/ml) will be applied locally as a gel (3 times a week) for a period of maximum three months or until intact skin.

Also known as: Desferal

Deferoxamine

Placebo DRUG

Placebo will be applied locally as a gel (3 times a week) for a period of maximum three months or until intact skin.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic foot ulcer (\> 1month) (at or below the ankle) grade 1A, 2A (University of Texas Wound Classification System) with an ulcer area between 150-350 mm2.
• No ulcer should present a moderate or severe infection at baseline. Concomitant treatment with systemic antibiotics at baseline is accepted if all ulcers meet none of the criteria defining moderate or severe infection.
• Toe/brachial index \>0.6 and/or Tcp02 \>50mmHg or ankle/brachial index \>0.65, or the pulses at dorsalis pedis/tibialis posterioris clearly palpable.
• Patient should be compliant to one of the accepted off-loading system.
• Patients will be able to provide written informed consent

You may not qualify if:

• Acute cardiovascular event (myocardial infarction/unstable angina, stroke) within three months prior to randomisation
• Subjects who have undergone vascular reconstruction or angioplasty less than 3 months prior to randomisation
• Decompensated congestive heart failure or functional class 3-4.
• Childbearing potential
• Impaired hepatic function (2 times upper normal limit of ASAT and ALAT)
• Severe renal failure (GFR calculated after Cockcroft's formula \<30 ml/min/1.73 m2)
• Ongoing treatment with immunosuppressive drugs
• HbA1c \>12 % (108 mmol/l)(12%)
• Polyglobulia (EVF\>0.60 men, EVF\> 0.56 women)
• Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol
• Malignancy other than basal-cell carcinoma and cervical carcinoma in situ, requiring any general, local, surgical or radiation therapy.
• History of alcohol or drug abuse
• Osteomyelitis defined as:
• There is a clinical suspicion of osteomyelitis;
• Ulcer considered for treatment is located at the site of a past amputation;

Sponsors & Collaborators

• Karolinska University Hospital: lead

Related Publications (21)

• Catrina SB, Okamoto K, Pereira T, Brismar K, Poellinger L. Hyperglycemia regulates hypoxia-inducible factor-1alpha protein stability and function. Diabetes. 2004 Dec;53(12):3226-32. doi: 10.2337/diabetes.53.12.3226.

  PMID: 15561954 BACKGROUND

• Catrina SB. Impaired hypoxia-inducible factor (HIF) regulation by hyperglycemia. J Mol Med (Berl). 2014 Oct;92(10):1025-34. doi: 10.1007/s00109-014-1166-x. Epub 2014 Jun 12.

  PMID: 25027070 BACKGROUND

• Kerr M, Rayman G, Jeffcoate WJ. Cost of diabetic foot disease to the National Health Service in England. Diabet Med. 2014 Dec;31(12):1498-504. doi: 10.1111/dme.12545. Epub 2014 Aug 1.

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• UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998 Sep 12;317(7160):703-13.

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• Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. Lancet. 2005 Nov 12;366(9498):1719-24. doi: 10.1016/S0140-6736(05)67698-2.

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• Apelqvist J, Larsson J, Agardh CD. Long-term prognosis for diabetic patients with foot ulcers. J Intern Med. 1993 Jun;233(6):485-91. doi: 10.1111/j.1365-2796.1993.tb01003.x.

  PMID: 8501419 BACKGROUND

• Jeffcoate WJ, Chipchase SY, Ince P, Game FL. Assessing the outcome of the management of diabetic foot ulcers using ulcer-related and person-related measures. Diabetes Care. 2006 Aug;29(8):1784-7. doi: 10.2337/dc06-0306.

  PMID: 16873780 BACKGROUND

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• Prompers L, Schaper N, Apelqvist J, Edmonds M, Jude E, Mauricio D, Uccioli L, Urbancic V, Bakker K, Holstein P, Jirkovska A, Piaggesi A, Ragnarson-Tennvall G, Reike H, Spraul M, Van Acker K, Van Baal J, Van Merode F, Ferreira I, Huijberts M. Prediction of outcome in individuals with diabetic foot ulcers: focus on the differences between individuals with and without peripheral arterial disease. The EURODIALE Study. Diabetologia. 2008 May;51(5):747-55. doi: 10.1007/s00125-008-0940-0. Epub 2008 Feb 23.

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  PMID: 11719828 BACKGROUND

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  PMID: 9562344 BACKGROUND

• Kaelin WG Jr. The von hippel-lindau tumor suppressor protein: an update. Methods Enzymol. 2007;435:371-83. doi: 10.1016/S0076-6879(07)35019-2.

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• Kaelin WG Jr. The von Hippel-Lindau tumor suppressor protein and clear cell renal carcinoma. Clin Cancer Res. 2007 Jan 15;13(2 Pt 2):680s-684s. doi: 10.1158/1078-0432.CCR-06-1865.

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• Semenza GL. Life with oxygen. Science. 2007 Oct 5;318(5847):62-4. doi: 10.1126/science.1147949.

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• Elson DA, Ryan HE, Snow JW, Johnson R, Arbeit JM. Coordinate up-regulation of hypoxia inducible factor (HIF)-1alpha and HIF-1 target genes during multi-stage epidermal carcinogenesis and wound healing. Cancer Res. 2000 Nov 1;60(21):6189-95.

  PMID: 11085544 BACKGROUND

• Fadini GP, Sartore S, Schiavon M, Albiero M, Baesso I, Cabrelle A, Agostini C, Avogaro A. Diabetes impairs progenitor cell mobilisation after hindlimb ischaemia-reperfusion injury in rats. Diabetologia. 2006 Dec;49(12):3075-84. doi: 10.1007/s00125-006-0401-6. Epub 2006 Oct 27.

  PMID: 17072586 BACKGROUND

• Gao W, Ferguson G, Connell P, Walshe T, Murphy R, Birney YA, O'Brien C, Cahill PA. High glucose concentrations alter hypoxia-induced control of vascular smooth muscle cell growth via a HIF-1alpha-dependent pathway. J Mol Cell Cardiol. 2007 Mar;42(3):609-19. doi: 10.1016/j.yjmcc.2006.12.006. Epub 2006 Dec 21.

  PMID: 17321542 BACKGROUND

• Botusan IR, Sunkari VG, Savu O, Catrina AI, Grunler J, Lindberg S, Pereira T, Yla-Herttuala S, Poellinger L, Brismar K, Catrina SB. Stabilization of HIF-1alpha is critical to improve wound healing in diabetic mice. Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19426-31. doi: 10.1073/pnas.0805230105. Epub 2008 Dec 4.

  PMID: 19057015 BACKGROUND

• Thangarajah H, Yao D, Chang EI, Shi Y, Jazayeri L, Vial IN, Galiano RD, Du XL, Grogan R, Galvez MG, Januszyk M, Brownlee M, Gurtner GC. The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues. Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13505-10. doi: 10.1073/pnas.0906670106. Epub 2009 Jul 28.

  PMID: 19666581 BACKGROUND

• Hou Z, Nie C, Si Z, Ma Y. Deferoxamine enhances neovascularization and accelerates wound healing in diabetic rats via the accumulation of hypoxia-inducible factor-1alpha. Diabetes Res Clin Pract. 2013 Jul;101(1):62-71. doi: 10.1016/j.diabres.2013.04.012. Epub 2013 May 28.

  PMID: 23726275 BACKGROUND

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  PMID: 7091534 BACKGROUND

MeSH Terms

Conditions

Diabetic Foot; Diabetes Mellitus; Foot Ulcer

Interventions

Deferoxamine

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Endocrine System Diseases; Diabetic Neuropathies; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Foot Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids

Study Officials

• Sergiu Catrina, MD/Ass.Prof.

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sergiu Catrina, MD/ass.Prof.

CONTACT

+46-8-51775449; sergiu.catrina@ki.se

Neda Rajamand Ekberg, MD/Ph.D.

CONTACT

+46-8-51770000; neda.ekberg@ki.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The drugs (active or placebo) will be supplied by the supervision of Medigelium AB and will have the same appearance.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated professor

Model Details: prospective, randomised, double-blind and placebo-controlled study with parallel groups, multiple centre trial.

Study Record Dates

• First Submitted: April 30, 2017
• First Posted: May 3, 2017
• Study Start: December 30, 2022
• Primary Completion: December 31, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: May 26, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share