Diabetic Foot UlcerNCT02251418
Shockwave Therapy of Chronic Diabetic Foot Ulcers
A study testing Extracorporeal shockwave therapy in people with Diabetic Foot Ulcer, run by Odense University Hospital at 1 site in Denmark.
Trial summary
Introduction: Foot ulcers are a feared complication among diabetic patients. The ulcers can cause pain, discomfort and reduced quality of life. The development of foot ulcers places the patients at a risk of amputation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Foot Ulcer
- What is being tested?
- Extracorporeal shockwave therapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteDenmark
- Study dates
- Feb 2015to Dec 2015
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients receiving care and treatment in OUH Wound Clinic (Odense University Hospital, Denmark) with a diabetic foot ulcer.
- Wagner groups 1 and 2 (Wagner Ulcer Classification System)
Who cannot join
- Patients with an ulcer duration of less than 2 months
- Ulcer area less than 0,5 x 0,5 cm (or less than 0,25 cm2)
- Patients who have had vascular surgery performed within the past 2 months
- Patients who cannot give informed consent
- Patients who do not read or speak danish
- Wagner groups 3 and 4 (Wagner Ulcer Classification System)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Extracorporeal Shockwave Therapy (ESWT) of Chronic Diabetic Foot Ulcers
Introduction:
Foot ulcers are a feared complication among diabetic patients. The ulcers can cause pain, discomfort and reduced quality of life. The development of foot ulcers places the patients at a risk of amputation. In the Danish Health Care System a substantial effort is done to prevent and treat diabetic foot ulcers. A constant research of how to treat these wounds is ongoing. The goal is to optimize wound healing and prevent amputations.
Read more
Extracorporeal shockwave therapy (ESWT) involves the use of a device that generates low-energy shockwaves through a headpiece, which is placed on the skin of the patient. A small amount of energy will be deposited in the tissue when shockwaves are applied. This stimulates the cells to produce substances that generate new vessels. No side effects to ESWT have been shown.
Purpose:
The investigators want to test whether shockwave therapy can improve wound healing among diabetic patients with foot ulcers.
Hypothesis:
The investigators hypothesize that shockwave therapy accelerates ulcer healing, increases blood flow, reduces pain, and has no side effects.
Method:
Patients who are interested in participation will be included in the study and divided by randomization into two groups of equal size. The first group is treated with ESWT in combination with regular guideline treatment. The second group is set up as control group and will only receive regular guideline treatment. The participants are examined in different ways to evaluate whether ESWT helps the healing of foot ulcers. The investigators want to measure tissue oxygen pressure and foot sense of touch. The foot ulcers are inspected for infection at every consultation, and a swab sample will be collected at enrollment. The size of the ulcers are measured and photographed each time. The investigators will count how many foot ulcers that are completely healed during the test period and measure the sizes of the remaining foot ulcers. The patients are asked to evaluate pain related to the foot ulcer. Data concerning participants' co morbidities and use of analgesic drugs are obtained from the patient journal and by patient interview.
Significance:
ESWT should be considered a supplement to existing clinical guidelines in wound management if shown to effectively help healing of diabetic foot ulcers. Improved healing should reduce the heavy workload on care and treatment regarding to these wounds. Hopefully, the frequency of amputations among diabetic patients will decline by implementing new treatment options for the diabetic foot.
Read the detailed description
[Introduction]
It is estimated that 5.5 % of the Danish population suffers from diabetes - corresponding to more than 320.000 persons. Among Danish diabetic patients the yearly incidence of foot ulcers is higher than 3.000 and the prevalence higher than 22.000. Diabetics have a lifetime risk of foot ulcers of 15 %.
Amputation is a possible consequence to having a diabetic foot ulcer. A 19-year follow-up study performed on newly diagnosed diabetics shows an incidence of amputation of 400 per 100.000 patient years.
Economical costs associated with a diabetic foot ulcer vary with the severity and treatment of the ulcer. In Denmark costs including hospitalized treatment, outpatient treatment, homecare and other social services have been calculated to (written in Danish kroner 2009):
- Healed foot ulcer without ischemia: 152.800
- Healed foot ulcer with ischemia: 252. 800
- Foot ulcer with minor amputation: 407.900
- Foot ulcer with major amputation: 597.300
Groups including foot ulcers with minor or major amputation comprise 5 % of the total number of diabetic foot ulcers (corresponding to 150 amputations per year). Total costs of diabetic foot ulcers are 793 million Danish kroner.
Foot ulcers reduce the patients' mobility and their quality of life. Amputation is among the most feared complications to diabetes and it affects patients' quality of life as much as heart failure and cerebral stroke.
The treatment of diabetic foot ulcers is in several places of Denmark taken care of by multidisciplinary teams. Thus metabolic control, wound debridement, vascular surgery, treatment of infections, pain relief, occupational therapy etc. is taken care of in one specialized hospital unit. Parallel to a reorganization of the Danish health system 2000 - 2011 there was a significant decline in diabetic major amputations. However, no decline has been seen in the group of minor amputations and it may be that patients are now identified earlier for amputation thereby avoiding major amputations. Conclusively, a number of diabetic ulcer patients still cannot be offered any other treatment than amputation.
It is important to develop supplementing treatment options for the worst cases of diabetic foot ulcers. The goal is that ulcer healing is optimized and fewer patients are amputated.
In the field of diabetic foot ulcers a substantial amount of research is going on trying to develop existing methods of treatment and finding new therapeutic techniques. Extracorporeal shockwave therapy (ESWT) is a promising new option for ulcer treatment. ESWT has long been known in kidney stone treatment, and more recently ESWT has been established as treatment to regional pain disorders (such as plantar fasciitis of the heel and lateral epicondylitis of the elbow) and non-union of long bone fractures. Furthermore, ischemic heart disease and Peyronies disease have been treated with ESWT. Some studies show positive results when treating foot ulcers with ESWT.
In physics, shockwaves are high fluctuations of acoustical energy. When applied to a tissue shockwaves may stimulate an anabolic cellular response, increased blood perfusion and neo-angiogenesis. Shockwaves may furthermore promote anti-inflammatory effects and pain regulation. On a molecular scale upregulation of TGF-beta1, VEGF, FGF-2 signaling together with increased levels of NO and substance P in the tissue is seen following ESWT. During wound healing NO has been shown to induce IGF release through NF-kappaB pathway. Regarding to anti-inflammatory effects, ESWT reduces the cellular expression of metalloproteases and interleukins.
Clinical studies testing foot ulcer ESWT have not shown any significant side effects to shockwave treatment. These studies conclude that ESWT is safe to use.
----------------------------------------------------------------------------------------------------------------
[Purpose]
The investigators want to test if low-energy ESWT can help healing of complex diabetic foot ulcers. The effect of ESWT will be evaluated by measuring wound sizes and numbers of total healing, perception of pain using visual analog scale. Measures of cutaneous oxygen tension and foot sense of feeling will be included as well.
----------------------------------------------------------------------------------------------------------------
[Hypothesis]
ESWT improves diabetic patients' healing of chronic foot ulcers. In this study the investigators expect to see a faster wound area reduction among patients treated with ESWT compared to control group only receiving treatment according to current clinical guidelines.
Primary outcome measure for ESWT is
- Shorter time wound healing
Secondary outcome measures for ESWT are
- Pain reduction
- Increased perfusion
- No side effects
[Method]
Recruitment of patients: 6 months consecutive identification and inclusion of patients in Wound Clinic, Department of Plastic Surgery OUH. Every year approximately 400 patients with new ulcers are referred to the clinic. Patients who are either newly referred or in advance related to the clinic can be offered participation.
Randomization: Participants will be randomized to either intervention group or control group using a computer-generated table indicating allocation.
Intervention group: ESWT as a supplement to treatment following current clinical guidelines.
Control group: Ulcer treatment following clinical guidelines.
ESWT: A total of 6 times treatment over a 3 week period. Intervals between ESWT will be 3 - 4 days. ESWT will be carried out using the DUOLITH SD1 T-Top shockwave device, STORZ MEDICAL AG. The device is CE mark registered for ESWT use.
Description of intervention course: Participants in this group will have 8 consultations in a 7 week period. 6 times ESWT followed by 2 times follow-up respectively 2 and 4 weeks after last ESWT.
Description of control course: Participants in this group will have 4 consultations in a 7 week period. First consultation by enrollment. Second, third, and fourth consultations respectively 3, 5, and 7 weeks after enrollment. These four consultations corresponds to intervention group consultation number 1, 6, 7, and 8.
Baseline data: By the first consultation participants will be characterized in regard to the following variables:
- Sex
- Age
- Comorbidity (quantified using Charlson Index)
- Medical treatment: antidiabetics, analgesics (relevant drugs are NSAIDs, neuroleptics and opioids), antihypertensives, statins / cholesterol lowering drugs
- Smoking habits and alcohol consumption
- Body Mass Index
- Marital status, educational level and type of profession
- Classification of foot ulcer using University of Texas Wound Score
- Biochemistry: HbA1c, CRP, leukocytes, s-Na, s-K, s-creatinine, s-alkaline phosphatase, s-lactate dehydrogenase, s-cholesterol levels
- Bacterial colonization of the ulcer
Biochemical parameters and medical treatment data will be obtained from the patient records. New blood samples will be taken if the patient records do not include relevant test results - furthermore results must not be more than 2 months old.
Patients enrolled in the study will have access to all usually offered ulcer treatment. Information about other treatment modalities and frequencies will be obtained from participants patient records and patient interviews.
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[Data handling]
Data will be noted in the REDCap online system. Data will be stored until study end. Analysis will be carried out using Stata software.
The study uses only one data collector who will also enter data in REDCap. However, if data are not available or missing, the specific measurements will be excluded from analysis. Missing data will be reported with published study results.
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[Statistics]
Average percentage reduction of ulcer area is the study's primary end-point. If data are normally distributed (determined by probit or logit plot) statistical analysis can be performed using Student's t-test. Non-normally distributed data can be analyzed using transformation of data or non-parametric statistics (Wilcoxon rank sum test or Mann-Whitney U-test). Other numerical data (cutaneous oxygen tension, pain scoring, use of analgesics) can be statistically evaluated in the same manner as ulcer area reduction.
Complete ulcer healing is regarded as binary end-point data. Healing proportions will be calculated and compared between intervention group and control group - risk ratio and confidence intervals will be determined. Significance of data will be tested using Pearson's chi-squared test (alternatively Fisher's exact test if data material is small / does not fit chi-test). Sense of touch data will be evaluated in the same way.
Comparison of patient's quality of life in intervention group and control group is based on average questionnaire scores.
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[Study power]
This study should be considered a pilot study. Earlier studies investigating ESWT ulcer treatment focus on study populations which are different from ours. The investigators consider our design to be unique since the investigators have not been able to identify earlier studies using a standard care control group to compare against intervention with 6 times ESWT in 3 weeks.
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[Project feasibility]
The project is carried out as an undergraduate research year in the period 1/9-2014 - 1/9-2015. Medical student Sune Møller Jeppesen is accepted as an undergraduate student from the Faculty of Health Science, University of Southern Denmark. The undergraduate student works under guidance from main supervisor Lars Lund, professor, MD, DMSci. Knud Bonnet Yderstræde, MD, PhD, and Benjamin Schnack Rasmussen, MD, PhD-student, are co-supervisors for the project. Primarily, the undergraduate student's work will involve ESWT consultations and data collection. The student will be trained in relevant techniques needed for measuring ESWT effects.
Office facilities are available for the undergraduate student at the Department of Urology. Consultation room and devices for clinical measurements are available at the Wound Clinic, Department of Plastic Surgery OUH. Shockwave device will be purchased (see budget information).
The project will be registered to relevant authorities including the Danish Data Protection Agency and the Committee for Health Research Ethics, Denmark.
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[Publication]
Trial results will be applied for publishing in an international scientific journal. Furthermore results will be presented at science conferences within the fields of interest.
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[Economy]
The investigators seek research funding from private and public organizations. The investigators apply for 120.000 Danish kroner (DKK) to cover 12 months undergraduate student salary and 371.125 DKK for shockwave device purchase. Costs related to office facilities are 14.500 DKK. Project overhead is 3 % of total costs. Total project costs are 520.794 DKK.
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[Significance of the project]
The project aims to evaluate healing effects of ESWT. If ESWT effectively can improve healing of complicated diabetic foot ulcers, ESWT should be considered for implementation in ulcer treatment clinical guidelines. Better ulcer healing can potentially improve patient's quality of life and decrease the number of diabetic patients who are being amputated (or at least postpone amputations). Later, research may be carried out to refine ulcer ESWT.
Proven ulcer healing effects of ESWT may also inspire future studies to test ESWT effects in the context of other clinical conditions. Possibly ESWT can be used in several settings where regenerative and anti-inflammatory effects are wanted.
- Conditions
- Diabetic Foot Ulcer
- Being tested
- Extracorporeal shockwave therapy
- Keywords
- Foot ulcer, diabetic, ESWT (Extracorporeal Shockwave Therapy), Endocrinology, Dermatology, Wound healing, Ischemia, Neovascularization, Physiologic, Pain management
- Medical subject headings
- Diabetic Foot, Ischemia, Neovascularization, Pathologic, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extracorporeal shockwave therapyDevice
Also called STORZ DUOLITH SD1 T-top shockwave device
| Study group | Role | What they receive |
|---|---|---|
| Extracorporeal shockwave therapy | Experimental | 6 times extracorporeal shockwave therapy in 3 weeks. This arm also receives standard care treatment. Receives: Device: Extracorporeal shockwave therapy |
| Control | No intervention | Standard care treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ulcer area
We will use digital photos to determine 49 days ulcer area and compare to trial entry.
Measured: 49 days after enrollment
Secondary outcomes (25)
Ulcer area (only intervention group)
We will use digital photos to determine 3-4 days ulcer area and compare to trial entry.
Measured: 3-4 days after enrollment
Ulcer area (only intervention group)
We will use digital photos to determine 6-7 days ulcer area and compare to trial entry.
Measured: 6-7 days after enrollment
Ulcer area (only intervention group)
We will use digital photos to determine 10-11 days ulcer area and compare to trial entry.
Measured: 10-11 days after enrollment
Ulcer area (only intervention group)
We will use digital photos to determine 13-14 days ulcer area and compare to trial entry.
Measured: 13-14 days after enrollment
Ulcer area (only intervention group)
We will use digital photos to determine 17-18 days ulcer area and compare to trial entry.
Measured: 17-18 days after enrollment
Oxygen tension
Cutaneous oxygen tension around ulcer
Measured: 21 days after enrollment
Oxygen tension
Cutaneous oxygen tension around ulcer
Measured: 35 days after enrollment
Oxygen tension
Cutaneous oxygen tension around ulcer
Measured: 49 days after enrollment
Pain
Pain regarding to the ulcer will be assessed using Visual Analog Scale (VAS)
Measured: 21 days after enrollment
Pain
Pain regarding to the ulcer will be assessed using Visual Analog Scale (VAS)
Measured: 35 days after enrollment
Pain
Pain regarding to the ulcer will be assessed using Visual Analog Scale (VAS)
Measured: 49 days after enrollment
Side effects
Side effects will be recorded by case history and clinical examination
Measured: 21 days after enrollment
Side effects
Side effects will be recorded by case history and clinical examination
Measured: 35 days after enrollment
Side effects
Side effects will be recorded by case history and clinical examination
Measured: 49 days after enrollment
Monofilament test
Skin sensitivity on the foot will be tested by performing standardized monofilament test. Binary outcome measure.
Measured: 21 days after enrollment
Monofilament test
Skin sensitivity on the foot will be tested by performing standardized monofilament test. Binary outcome measure.
Measured: 35 days after enrollment
Monofilament test
Skin sensitivity on the foot will be tested by performing standardized monofilament test. Binary outcome measure.
Measured: 49 days after enrollment
Use of analgetics
Participants use of analgetics will be recorded. Type and dosis will be noted.
Measured: 21 days after enrollment
Use of analgetics
Participants use of analgetics will be recorded. Type and dosis will be noted.
Measured: 35 days after enrollment
Use of analgetics
Participants use of analgetics will be recorded. Type and dosis will be noted.
Measured: 49 days after enrollment
Complete ulcer healing
If ulcer is completely healed, this including time to event will be noted
Measured: 21 days after enrollment
Complete ulcer healing
If ulcer is completely healed, this including time to event will be noted
Measured: 35 days after enrollment
Complete ulcer healing
If ulcer is completely healed, this including time to event will be noted
Measured: 49 days after enrollment
Ulcer area
We will use digital photos to determine 21 days ulcer area and compare to trial entry.
Measured: 21 days after enrollment
Ulcer area
We will use digital photos to determine 21 days ulcer area and compare to trial entry.
Measured: 35 days after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2014 (estimated)
- Study startFeb 2015
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Diabetic Foot UlcerStudies of the same condition, open and under way.
- More trials run by Odense University HospitalThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Odense University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Southern Denmark
- Responsible party
- Principal investigator, Sune Moeller Jeppesen, Odense University Hospital
- Investigators
- Lars Lund, Professor, Study director, Odense University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02251418
- Sponsor's protocol ID
- 2014-ESWTULCER
- Status last verified
- Mar 2016
- First submitted
- 25 Sep 2014
- Last updated
- 30 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bruun C, Siersma V, Guassora AD, Holstein P, de Fine Olivarius N. Amputations and foot ulcers in patients newly diagnosed with type 2 diabetes mellitus and observed for 19 years. The role of age, gender and co-morbidity. Diabet Med. 2013 Aug;30(8):964-72. doi: 10.1111/dme.12196. Epub 2013 Apr 26.
PubMed 23617411Siersma V, Thorsen H, Holstein PE, Kars M, Apelqvist J, Jude EB, Piaggesi A, Bakker K, Edmonds M, Jirkovska A, Mauricio D, Ragnarson Tennvall G, Reike H, Spraul M, Uccioli L, Urbancic V, van Acker K, van Baal J, Schaper NC. Importance of factors determining the low health-related quality of life in people presenting with a diabetic foot ulcer: the Eurodiale study. Diabet Med. 2013 Nov;30(11):1382-7. doi: 10.1111/dme.12254. Epub 2013 Jul 15.
PubMed 23758490Vileikyte L. Psychosocial and behavioral aspects of diabetic foot lesions. Curr Diab Rep. 2008 Apr;8(2):119-25. doi: 10.1007/s11892-008-0022-1.
PubMed 18445354Goodridge D, Trepman E, Embil JM. Health-related quality of life in diabetic patients with foot ulcers: literature review. J Wound Ostomy Continence Nurs. 2005 Nov-Dec;32(6):368-77. doi: 10.1097/00152192-200511000-00007.
PubMed 16301902Alva M, Gray A, Mihaylova B, Clarke P. The effect of diabetes complications on health-related quality of life: the importance of longitudinal data to address patient heterogeneity. Health Econ. 2014 Apr;23(4):487-500. doi: 10.1002/hec.2930. Epub 2013 Jul 11.
PubMed 23847044Hirai FE, Tielsch JM, Klein BE, Klein R. Ten-year change in self-rated quality of life in a type 1 diabetes population: Wisconsin Epidemiologic Study of Diabetic Retinopathy. Qual Life Res. 2013 Aug;22(6):1245-53. doi: 10.1007/s11136-012-0245-0. Epub 2012 Aug 8.
PubMed 22872499Jorgensen ME, Almdal TP, Faerch K. Reduced incidence of lower-extremity amputations in a Danish diabetes population from 2000 to 2011. Diabet Med. 2014 Apr;31(4):443-7. doi: 10.1111/dme.12320. Epub 2013 Oct 21.
PubMed 24111834Game FL, Hinchliffe RJ, Apelqvist J, Armstrong DG, Bakker K, Hartemann A, Londahl M, Price PE, Jeffcoate WJ. A systematic review of interventions to enhance the healing of chronic ulcers of the foot in diabetes. Diabetes Metab Res Rev. 2012 Feb;28 Suppl 1:119-41. doi: 10.1002/dmrr.2246.
PubMed 22271737Gottrup F, Apelqvist J. Present and new techniques and devices in the treatment of DFU: a critical review of evidence. Diabetes Metab Res Rev. 2012 Feb;28 Suppl 1:64-71. doi: 10.1002/dmrr.2242.
PubMed 22271726Wang CJ. Extracorporeal shockwave therapy in musculoskeletal disorders. J Orthop Surg Res. 2012 Mar 20;7:11. doi: 10.1186/1749-799X-7-11.
PubMed 22433113Zimpfer D, Aharinejad S, Holfeld J, Thomas A, Dumfarth J, Rosenhek R, Czerny M, Schaden W, Gmeiner M, Wolner E, Grimm M. Direct epicardial shock wave therapy improves ventricular function and induces angiogenesis in ischemic heart failure. J Thorac Cardiovasc Surg. 2009 Apr;137(4):963-70. doi: 10.1016/j.jtcvs.2008.11.006.
PubMed 19327525Kiyota H, Ohishi Y, Asano K, Hasegawa N, Madarame J, Miki K, Kato N, Kimura T, Ishiyama T, Maeda S, Shimomura T, Shiono Y, Miki J. Extracorporeal shock wave treatment for Peyronie's disease using EDAP LT-02; preliminary results. Int J Urol. 2002 Feb;9(2):110-3. doi: 10.1046/j.1442-2042.2002.00430.x. No abstract available.
PubMed 12033197Schaden W, Thiele R, Kolpl C, Pusch M, Nissan A, Attinger CE, Maniscalco-Theberge ME, Peoples GE, Elster EA, Stojadinovic A. Shock wave therapy for acute and chronic soft tissue wounds: a feasibility study. J Surg Res. 2007 Nov;143(1):1-12. doi: 10.1016/j.jss.2007.01.009. Epub 2007 Sep 27.
PubMed 17904157Saggini R, Figus A, Troccola A, Cocco V, Saggini A, Scuderi N. Extracorporeal shock wave therapy for management of chronic ulcers in the lower extremities. Ultrasound Med Biol. 2008 Aug;34(8):1261-71. doi: 10.1016/j.ultrasmedbio.2008.01.010. Epub 2008 Apr 18.
PubMed 18394777Wang CJ, Kuo YR, Wu RW, Liu RT, Hsu CS, Wang FS, Yang KD. Extracorporeal shockwave treatment for chronic diabetic foot ulcers. J Surg Res. 2009 Mar;152(1):96-103. doi: 10.1016/j.jss.2008.01.026. Epub 2008 Mar 7.
PubMed 18619622
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Extracorporeal Shockwave Therapy (ESWT) of Chronic Diabetic Foot Ulcers
- ClinicalTrials.gov ID
- NCT02251418
- Acronym / sponsor ID
- 2014-ESWTULCER
- Conditions
- Diabetic Foot Ulcer
- Keywords
- Foot ulcer, diabetic, ESWT (Extracorporeal Shockwave Therapy), Endocrinology, Dermatology, Wound healing, Ischemia, Neovascularization, Physiologic, Pain management
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Odense University HospitalUniversity, hospital or other
- Collaborators
- University of Southern Denmark
- Study start
- Feb 2015
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 29 Sep 2014 (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.
Introduction:
Foot ulcers are a feared complication among diabetic patients. The ulcers can cause pain, discomfort and reduced quality of life. The development of foot ulcers places the patients at a risk of amputation. In the Danish Health Care System a substantial effort is done to prevent and treat diabetic foot ulcers. A constant research of how to treat these wounds is ongoing. The goal is to optimize wound healing and prevent amputations.
Extracorporeal shockwave therapy (ESWT) involves the use of a device that generates low-energy shockwaves through a headpiece, which is placed on the skin of the patient. A small amount of energy will be deposited in the tissue when shockwaves are applied. This stimulates the cells to produce substances that generate new vessels. No side effects to ESWT have been shown.
Purpose:
The investigators want to test whether shockwave therapy can improve wound healing among diabetic patients with foot ulcers.
Hypothesis:
The investigators hypothesize that shockwave therapy accelerates ulcer healing, increases blood flow, reduces pain, and has no side effects.
Method:
Patients who are interested in participation will be included in the study and divided by randomization into two groups of equal size. The first group is treated with ESWT in combination with regular guideline treatment. The second group is set up as control group and will only receive regular guideline treatment. The participants are examined in different ways to evaluate whether ESWT helps the healing of foot ulcers. The investigators want to measure tissue oxygen pressure and foot sense of touch. The foot ulcers are inspected for infection at every consultation, and a swab sample will be collected at enrollment. The size of the ulcers are measured and photographed each time. The investigators will count how many foot ulcers that are completely healed during the test period and measure the sizes of the remaining foot ulcers. The patients are asked to evaluate pain related to the foot ulcer. Data concerning participants' co morbidities and use of analgesic drugs are obtained from the patient journal and by patient interview.
Significance:
ESWT should be considered a supplement to existing clinical guidelines in wound management if shown to effectively help healing of diabetic foot ulcers. Improved healing should reduce the heavy workload on care and treatment regarding to these wounds. Hopefully, the frequency of amputations among diabetic patients will decline by implementing new treatment options for the diabetic foot.
Detailed description
[Introduction]
It is estimated that 5.5 % of the Danish population suffers from diabetes - corresponding to more than 320.000 persons. Among Danish diabetic patients the yearly incidence of foot ulcers is higher than 3.000 and the prevalence higher than 22.000. Diabetics have a lifetime risk of foot ulcers of 15 %.
Amputation is a possible consequence to having a diabetic foot ulcer. A 19-year follow-up study performed on newly diagnosed diabetics shows an incidence of amputation of 400 per 100.000 patient years.
Economical costs associated with a diabetic foot ulcer vary with the severity and treatment of the ulcer. In Denmark costs including hospitalized treatment, outpatient treatment, homecare and other social services have been calculated to (written in Danish kroner 2009):
- Healed foot ulcer without ischemia: 152.800
- Healed foot ulcer with ischemia: 252. 800
- Foot ulcer with minor amputation: 407.900
- Foot ulcer with major amputation: 597.300
Groups including foot ulcers with minor or major amputation comprise 5 % of the total number of diabetic foot ulcers (corresponding to 150 amputations per year). Total costs of diabetic foot ulcers are 793 million Danish kroner.
Foot ulcers reduce the patients' mobility and their quality of life. Amputation is among the most feared complications to diabetes and it affects patients' quality of life as much as heart failure and cerebral stroke.
The treatment of diabetic foot ulcers is in several places of Denmark taken care of by multidisciplinary teams. Thus metabolic control, wound debridement, vascular surgery, treatment of infections, pain relief, occupational therapy etc. is taken care of in one specialized hospital unit. Parallel to a reorganization of the Danish health system 2000 - 2011 there was a significant decline in diabetic major amputations. However, no decline has been seen in the group of minor amputations and it may be that patients are now identified earlier for amputation thereby avoiding major amputations. Conclusively, a number of diabetic ulcer patients still cannot be offered any other treatment than amputation.
It is important to develop supplementing treatment options for the worst cases of diabetic foot ulcers. The goal is that ulcer healing is optimized and fewer patients are amputated.
In the field of diabetic foot ulcers a substantial amount of research is going on trying to develop existing methods of treatment and finding new therapeutic techniques. Extracorporeal shockwave therapy (ESWT) is a promising new option for ulcer treatment. ESWT has long been known in kidney stone treatment, and more recently ESWT has been established as treatment to regional pain disorders (such as plantar fasciitis of the heel and lateral epicondylitis of the elbow) and non-union of long bone fractures. Furthermore, ischemic heart disease and Peyronies disease have been treated with ESWT. Some studies show positive results when treating foot ulcers with ESWT.
In physics, shockwaves are high fluctuations of acoustical energy. When applied to a tissue shockwaves may stimulate an anabolic cellular response, increased blood perfusion and neo-angiogenesis. Shockwaves may furthermore promote anti-inflammatory effects and pain regulation. On a molecular scale upregulation of TGF-beta1, VEGF, FGF-2 signaling together with increased levels of NO and substance P in the tissue is seen following ESWT. During wound healing NO has been shown to induce IGF release through NF-kappaB pathway. Regarding to anti-inflammatory effects, ESWT reduces the cellular expression of metalloproteases and interleukins.
Clinical studies testing foot ulcer ESWT have not shown any significant side effects to shockwave treatment. These studies conclude that ESWT is safe to use.
----------------------------------------------------------------------------------------------------------------
[Purpose]
The investigators want to test if low-energy ESWT can help healing of complex diabetic foot ulcers. The effect of ESWT will be evaluated by measuring wound sizes and numbers of total healing, perception of pain using visual analog scale. Measures of cutaneous oxygen tension and foot sense of feeling will be included as well.
----------------------------------------------------------------------------------------------------------------
[Hypothesis]
ESWT improves diabetic patients' healing of chronic foot ulcers. In this study the investigators expect to see a faster wound area reduction among patients treated with ESWT compared to control group only receiving treatment according to current clinical guidelines.
Primary outcome measure for ESWT is
- Shorter time wound healing
Secondary outcome measures for ESWT are
- Pain reduction
- Increased perfusion
- No side effects
[Method]
Recruitment of patients: 6 months consecutive identification and inclusion of patients in Wound Clinic, Department of Plastic Surgery OUH. Every year approximately 400 patients with new ulcers are referred to the clinic. Patients who are either newly referred or in advance related to the clinic can be offered participation.
Randomization: Participants will be randomized to either intervention group or control group using a computer-generated table indicating allocation.
Intervention group: ESWT as a supplement to treatment following current clinical guidelines.
Control group: Ulcer treatment following clinical guidelines.
ESWT: A total of 6 times treatment over a 3 week period. Intervals between ESWT will be 3 - 4 days. ESWT will be carried out using the DUOLITH SD1 T-Top shockwave device, STORZ MEDICAL AG. The device is CE mark registered for ESWT use.
Description of intervention course: Participants in this group will have 8 consultations in a 7 week period. 6 times ESWT followed by 2 times follow-up respectively 2 and 4 weeks after last ESWT.
Description of control course: Participants in this group will have 4 consultations in a 7 week period. First consultation by enrollment. Second, third, and fourth consultations respectively 3, 5, and 7 weeks after enrollment. These four consultations corresponds to intervention group consultation number 1, 6, 7, and 8.
Baseline data: By the first consultation participants will be characterized in regard to the following variables:
- Sex
- Age
- Comorbidity (quantified using Charlson Index)
- Medical treatment: antidiabetics, analgesics (relevant drugs are NSAIDs, neuroleptics and opioids), antihypertensives, statins / cholesterol lowering drugs
- Smoking habits and alcohol consumption
- Body Mass Index
- Marital status, educational level and type of profession
- Classification of foot ulcer using University of Texas Wound Score
- Biochemistry: HbA1c, CRP, leukocytes, s-Na, s-K, s-creatinine, s-alkaline phosphatase, s-lactate dehydrogenase, s-cholesterol levels
- Bacterial colonization of the ulcer
Biochemical parameters and medical treatment data will be obtained from the patient records. New blood samples will be taken if the patient records do not include relevant test results - furthermore results must not be more than 2 months old.
Patients enrolled in the study will have access to all usually offered ulcer treatment. Information about other treatment modalities and frequencies will be obtained from participants patient records and patient interviews.
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[Data handling]
Data will be noted in the REDCap online system. Data will be stored until study end. Analysis will be carried out using Stata software.
The study uses only one data collector who will also enter data in REDCap. However, if data are not available or missing, the specific measurements will be excluded from analysis. Missing data will be reported with published study results.
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[Statistics]
Average percentage reduction of ulcer area is the study's primary end-point. If data are normally distributed (determined by probit or logit plot) statistical analysis can be performed using Student's t-test. Non-normally distributed data can be analyzed using transformation of data or non-parametric statistics (Wilcoxon rank sum test or Mann-Whitney U-test). Other numerical data (cutaneous oxygen tension, pain scoring, use of analgesics) can be statistically evaluated in the same manner as ulcer area reduction.
Complete ulcer healing is regarded as binary end-point data. Healing proportions will be calculated and compared between intervention group and control group - risk ratio and confidence intervals will be determined. Significance of data will be tested using Pearson's chi-squared test (alternatively Fisher's exact test if data material is small / does not fit chi-test). Sense of touch data will be evaluated in the same way.
Comparison of patient's quality of life in intervention group and control group is based on average questionnaire scores.
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[Study power]
This study should be considered a pilot study. Earlier studies investigating ESWT ulcer treatment focus on study populations which are different from ours. The investigators consider our design to be unique since the investigators have not been able to identify earlier studies using a standard care control group to compare against intervention with 6 times ESWT in 3 weeks.
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[Project feasibility]
The project is carried out as an undergraduate research year in the period 1/9-2014 - 1/9-2015. Medical student Sune Møller Jeppesen is accepted as an undergraduate student from the Faculty of Health Science, University of Southern Denmark. The undergraduate student works under guidance from main supervisor Lars Lund, professor, MD, DMSci. Knud Bonnet Yderstræde, MD, PhD, and Benjamin Schnack Rasmussen, MD, PhD-student, are co-supervisors for the project. Primarily, the undergraduate student's work will involve ESWT consultations and data collection. The student will be trained in relevant techniques needed for measuring ESWT effects.
Office facilities are available for the undergraduate student at the Department of Urology. Consultation room and devices for clinical measurements are available at the Wound Clinic, Department of Plastic Surgery OUH. Shockwave device will be purchased (see budget information).
The project will be registered to relevant authorities including the Danish Data Protection Agency and the Committee for Health Research Ethics, Denmark.
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[Publication]
Trial results will be applied for publishing in an international scientific journal. Furthermore results will be presented at science conferences within the fields of interest.
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[Economy]
The investigators seek research funding from private and public organizations. The investigators apply for 120.000 Danish kroner (DKK) to cover 12 months undergraduate student salary and 371.125 DKK for shockwave device purchase. Costs related to office facilities are 14.500 DKK. Project overhead is 3 % of total costs. Total project costs are 520.794 DKK.
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[Significance of the project]
The project aims to evaluate healing effects of ESWT. If ESWT effectively can improve healing of complicated diabetic foot ulcers, ESWT should be considered for implementation in ulcer treatment clinical guidelines. Better ulcer healing can potentially improve patient's quality of life and decrease the number of diabetic patients who are being amputated (or at least postpone amputations). Later, research may be carried out to refine ulcer ESWT.
Proven ulcer healing effects of ESWT may also inspire future studies to test ESWT effects in the context of other clinical conditions. Possibly ESWT can be used in several settings where regenerative and anti-inflammatory effects are wanted.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Extracorporeal shockwave therapy | Experimental | Device: Extracorporeal shockwave therapy6 times extracorporeal shockwave therapy in 3 weeks. This arm also receives standard care treatment. |
| Control | No intervention | –Standard care treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients receiving care and treatment in OUH Wound Clinic (Odense University Hospital, Denmark) with a diabetic foot ulcer.
- Wagner groups 1 and 2 (Wagner Ulcer Classification System)
Key exclusion criteria (6 listed)
- Patients with an ulcer duration of less than 2 months
- Ulcer area less than 0,5 x 0,5 cm (or less than 0,25 cm2)
- Patients who have had vascular surgery performed within the past 2 months
- Patients who cannot give informed consent
- Patients who do not read or speak danish
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 |
|---|---|---|
| Extracorporeal shockwave therapyAlso: STORZ DUOLITH SD1 T-top shockwave device | Device | Extracorporeal shockwave therapy |
Primary outcome
Ulcer area
Time frame: 49 days after enrollment
We will use digital photos to determine 49 days ulcer area and compare to trial entry.
25 secondary outcomes
Ulcer area (only intervention group)
Time frame: 3-4 days after enrollment
Ulcer area (only intervention group)
Time frame: 6-7 days after enrollment
Ulcer area (only intervention group)
Time frame: 10-11 days after enrollment
Ulcer area (only intervention group)
Time frame: 13-14 days after enrollment
Ulcer area (only intervention group)
Time frame: 17-18 days after enrollment
Oxygen tension
Time frame: 21 days after enrollment
Oxygen tension
Time frame: 35 days after enrollment
Oxygen tension
Time frame: 49 days after enrollment
Pain
Time frame: 21 days after enrollment
Pain
Time frame: 35 days after enrollment
Pain
Time frame: 49 days after enrollment
Side effects
Time frame: 21 days after enrollment
Side effects
Time frame: 35 days after enrollment
Side effects
Time frame: 49 days after enrollment
Monofilament test
Time frame: 21 days after enrollment
Monofilament test
Time frame: 35 days after enrollment
Monofilament test
Time frame: 49 days after enrollment
Use of analgetics
Time frame: 21 days after enrollment
Use of analgetics
Time frame: 35 days after enrollment
Use of analgetics
Time frame: 49 days after enrollment
Complete ulcer healing
Time frame: 21 days after enrollment
Complete ulcer healing
Time frame: 35 days after enrollment
Complete ulcer healing
Time frame: 49 days after enrollment
Ulcer area
Time frame: 21 days after enrollment
Ulcer area
Time frame: 35 days after enrollment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2016.
- Background: PubMed 23617411Bruun C, Siersma V, Guassora AD, Holstein P, de Fine Olivarius N. Amputations and foot ulcers in patients newly diagnosed with type 2 diabetes mellitus and observed for 19 years. The role of age, gender and co-morbidity. Diabet Med. 2013 Aug;30(8):964-72. doi: 10.1111/dme.12196. Epub 2013 Apr 26.
- Background: PubMed 23758490Siersma V, Thorsen H, Holstein PE, Kars M, Apelqvist J, Jude EB, Piaggesi A, Bakker K, Edmonds M, Jirkovska A, Mauricio D, Ragnarson Tennvall G, Reike H, Spraul M, Uccioli L, Urbancic V, van Acker K, van Baal J, Schaper NC. Importance of factors determining the low health-related quality of life in people presenting with a diabetic foot ulcer: the Eurodiale study. Diabet Med. 2013 Nov;30(11):1382-7. doi: 10.1111/dme.12254. Epub 2013 Jul 15.
- Background: PubMed 18445354Vileikyte L. Psychosocial and behavioral aspects of diabetic foot lesions. Curr Diab Rep. 2008 Apr;8(2):119-25. doi: 10.1007/s11892-008-0022-1.
- Background: PubMed 16301902Goodridge D, Trepman E, Embil JM. Health-related quality of life in diabetic patients with foot ulcers: literature review. J Wound Ostomy Continence Nurs. 2005 Nov-Dec;32(6):368-77. doi: 10.1097/00152192-200511000-00007.
- Background: PubMed 23847044Alva M, Gray A, Mihaylova B, Clarke P. The effect of diabetes complications on health-related quality of life: the importance of longitudinal data to address patient heterogeneity. Health Econ. 2014 Apr;23(4):487-500. doi: 10.1002/hec.2930. Epub 2013 Jul 11.
- Background: PubMed 22872499Hirai FE, Tielsch JM, Klein BE, Klein R. Ten-year change in self-rated quality of life in a type 1 diabetes population: Wisconsin Epidemiologic Study of Diabetic Retinopathy. Qual Life Res. 2013 Aug;22(6):1245-53. doi: 10.1007/s11136-012-0245-0. Epub 2012 Aug 8.
- Background: PubMed 24111834Jorgensen ME, Almdal TP, Faerch K. Reduced incidence of lower-extremity amputations in a Danish diabetes population from 2000 to 2011. Diabet Med. 2014 Apr;31(4):443-7. doi: 10.1111/dme.12320. Epub 2013 Oct 21.
- Background: PubMed 22271737Game FL, Hinchliffe RJ, Apelqvist J, Armstrong DG, Bakker K, Hartemann A, Londahl M, Price PE, Jeffcoate WJ. A systematic review of interventions to enhance the healing of chronic ulcers of the foot in diabetes. Diabetes Metab Res Rev. 2012 Feb;28 Suppl 1:119-41. doi: 10.1002/dmrr.2246.
- Background: PubMed 22271726Gottrup F, Apelqvist J. Present and new techniques and devices in the treatment of DFU: a critical review of evidence. Diabetes Metab Res Rev. 2012 Feb;28 Suppl 1:64-71. doi: 10.1002/dmrr.2242.
- Background: PubMed 22433113Wang CJ. Extracorporeal shockwave therapy in musculoskeletal disorders. J Orthop Surg Res. 2012 Mar 20;7:11. doi: 10.1186/1749-799X-7-11.
- Background: PubMed 19327525Zimpfer D, Aharinejad S, Holfeld J, Thomas A, Dumfarth J, Rosenhek R, Czerny M, Schaden W, Gmeiner M, Wolner E, Grimm M. Direct epicardial shock wave therapy improves ventricular function and induces angiogenesis in ischemic heart failure. J Thorac Cardiovasc Surg. 2009 Apr;137(4):963-70. doi: 10.1016/j.jtcvs.2008.11.006.
- Background: PubMed 12033197Kiyota H, Ohishi Y, Asano K, Hasegawa N, Madarame J, Miki K, Kato N, Kimura T, Ishiyama T, Maeda S, Shimomura T, Shiono Y, Miki J. Extracorporeal shock wave treatment for Peyronie's disease using EDAP LT-02; preliminary results. Int J Urol. 2002 Feb;9(2):110-3. doi: 10.1046/j.1442-2042.2002.00430.x. No abstract available.
- Statens Serum Institut (SSI) is responsible for research-based health surveillance, rational use of IT in the Danish healthcare system and prevention and control of infectious diseases, biological threats and congenital disorders.Link provided by the sponsor.
- The Danish Health and Medicines Authority (Danish: Sundhedsstyrelsen) is the supreme health and pharmaceutical authority in Denmark.Link provided by the sponsor.
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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.
Lars Lund, Professor study director
Odense University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Extracorporeal shockwave therapy in people with Diabetic Foot Ulcer, run by Odense University Hospital at 1 site in Denmark.
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 2 inclusion and 6 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 30 Mar 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 Denmark. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Ulcer area (time frame: 49 days after enrollment). 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 NCT02251418, which also lists 20 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 30 Mar 2016.