Passive Training as a Treatment for Diabetic Foot Ulcers

NCT ID: NCT02785198

Last Updated: 2020-02-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-04-30

Study Completion Date

2018-07-31

Brief Summary

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Overall project design: This PhD project involves a randomized study on diabetic individuals with healing resistant wounds, comparing the effect of passive movement of the lower limb with standard treatment of diabetic wounds.

How to effectively improve the condition of peripheral arterial disease is limited. The primary purpose of this study is to uncover whether passive movement of the lower limb will influence muscle oxygen demand and thereby increasing blood flow. An increase in muscle oxygen demand is likely to increase both blood flow rate and the number of capillaries, which would induce the healing of wounds, that were not previously possible.

The secondary purpose is to increase understanding of the pathophysiological processes in wound healing through the study of biochemical markers of vascularization, inflammation and stem cell recruitment in blood samples. Further on analyzing the skin and muscle biopsies of the number and quality of endothelial cells and Capillary density and to develop new quantifiable methods to evaluate wound healing in.

The project is a randomized trial, consisting of simple passive training to improve blood vessel function, increase the growth of the smallest blood vessels, thereby preventing ulceration and ultimately amputation.

Detailed Description

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Background information

Diabetic foot ulcers are one of the most frequent and serious complication in diabetes mellitus. Despite attempts of prophylaxis\*, only two-thirds of the diabetic foot ulcers eventually heal, and up to 15-20% will ultimately require a minor or major amputation (Major lower extremity amputation is defined as through or above the ankle joint, and minor amputations is below the ankle joint. The incidence of diabetes is growing, but the multifactorial causes of impaired healing of chronic diabetic ulcers are still not well understood.

The diabetic foot ulcers are known to reduce the quality of life for patients both psychically and psychologically and therefore further investigation in new treatment options is plausible. Current knowledge regarding how to improve the condition in the beginning phase of peripheral artery disease (PAD) is limited. Investigators know that high oxygen tension and perfusion of the limb as well as an adequate density of microvessels in the tissue, is essential to wound healing. Therefore, interventions that increase blood flow and promote microcirculatory growth are likely to be beneficial in the treatment of wound healing.

\*Dressings, debridement, compression, clinical observation, antibiotics and glycemic control

It has been reported that passive training consisting of knee flexion/extension in a kinetic machine has a beneficial effect on up regulation of growth factors, remicrovascularization and improved blood flow. Høier et al described that passive movement of the leg induced a two-fold elevation in blood flow, elevation of angiogenic factors and initiates capillarization in skeletal muscle. All three factors are often impaired in the diabetic leg, which results in poor wound healing.

Due to the typical localization of the diabetic foot ulcers, this patient group is unable to exercise properly. Therefore will the investigators use a recent innovative model for the improvement of the limb microcirculation, developed at the Department of Nutrition, Exercise and Sports, University of Copenhagen, involving passive movement of the lower leg, for inducing increased blood flow and microcirculatory growth.

Rationale for the trial Diabetic patients have impaired wound healing due to multifactorial causes. The investigators know that high oxygen tension, and perfusion is essential to wound healing, and according to Høier et al's study, passive training can increase the perfusion and elevate proangiogenic factors in both young healthy males and peripheral artery disease (PAD) patients.

Null hypothesis:

1. Passive training does not lead to enhanced healing of diabetic foot ulcers.
2. Passive training of the lower limb does not affect perfusion of the trained limb.

Perspective:

This projects aim is to discover that passive training of the lower limb will increase the healing in diabetic foot ulcers. In addition, present a new treatment offer to diabetic patients with ulcers, who are not able to heal properly or perform active exercises. The investigators hope to see that the benefits of training and accelerated healing affect the PROM's.

Further on to present new knowledge of the specific molecular and functional changes that occur in the tissue during wound healing. This knowledge will be very important to improve our understanding of why ulcerations occur and why the tissue begins to decompose.

This is a prospective, randomized, single-blinded, parallel controlled design trial in subjects with diabetes mellitus investigating passive training as a treatment for the diabetic ulcer. The participants are randomized to either a control group or intervention.

The control group receiving standard wound treatment, and an intervention group receiving standard wound treatment, and passive training exercises for 8 weeks. The participants will be followed for 16 weeks or until clinical wound healing. All participants will receive standard wound care consisting of debridement, dressings, compression, offloading footwear and if necessary antibiotics The comparison groups should be as similar as possible as regard to important participant characteristics that might influence the response to the intervention. Therefore, a block randomization to ensure that equal numbers of participants with a characteristic thought to affect prognosis or response to the intervention, will be allocated to each comparison group.

Conditions

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Diabetic Foot Ulcers

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Control group

A control group receiving standard wound treatment consisting of debridement, dressings, compression, offloading footwear and if necessary antibiotics.

Group Type NO_INTERVENTION

No interventions assigned to this group

Passive training group

An Intervention group doing passive exercise for 8 weeks in knee extensor machine, and receiving standard wound treatment consisting of debridement, dressings, compression, offloading footwear and if necessary antibiotics.

Group Type EXPERIMENTAL

Passive knee extensor machine

Intervention Type DEVICE

The passive training machine, moves both legs from flexion to extension and back, 60 times per minute in 1 hour, 3 times per week. ROM is 60 degrees

Interventions

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Passive knee extensor machine

The passive training machine, moves both legs from flexion to extension and back, 60 times per minute in 1 hour, 3 times per week. ROM is 60 degrees

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
2. Diabetes mellitus according to the World Health Organisation (WHO) criteria (see http://www.who.int/diabetes/publications/en/ ) and a stable treatment treated in a period of 14 days prior to screening with insulin or an oral antidiabetic agent. Stable is defined as stable HBA1c.

4\. Foot ulcer: size: diameter \> 1cm. Duration of wound \> 6 weeks Location: Full thickness skin defect distal to the malleoli.

5\. Male or female, age \>18 years at the time of signing informed consent. 6. Non-dementia diagnosis.

Exclusion Criteria

1. Major infection; acute cellulitis, osteomyelitis or gangrene anywhere in the affected extremity.
2. Malignant disease
3. Major traumatic tissue damage.
4. Major lower extremity amputation.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Copenhagen

OTHER

Sponsor Role collaborator

Herlev Hospital

OTHER

Sponsor Role lead

Responsible Party

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Tue Smith Jørgensen

Medical Doctor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Tue Smith Joergensen, MD

Role: PRINCIPAL_INVESTIGATOR

Herlev and Gentofte Hospital, The Department of Orthopedics

Locations

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Herlev Hospital

Herlev, Capital Region of Denmark, Denmark

Site Status

Countries

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Denmark

References

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Moxey PW, Gogalniceanu P, Hinchliffe RJ, Loftus IM, Jones KJ, Thompson MM, Holt PJ. Lower extremity amputations--a review of global variability in incidence. Diabet Med. 2011 Oct;28(10):1144-53. doi: 10.1111/j.1464-5491.2011.03279.x.

Reference Type BACKGROUND
PMID: 21388445 (View on PubMed)

Tennvall GR, Apelqvist J, Eneroth M. Costs of deep foot infections in patients with diabetes mellitus. Pharmacoeconomics. 2000 Sep;18(3):225-38. doi: 10.2165/00019053-200018030-00003.

Reference Type BACKGROUND
PMID: 11147390 (View on PubMed)

Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights. Adv Ther. 2014 Aug;31(8):817-36. doi: 10.1007/s12325-014-0140-x. Epub 2014 Jul 29.

Reference Type BACKGROUND
PMID: 25069580 (View on PubMed)

Hinchliffe RJ, Valk GD, Apelqvist J, Armstrong DG, Bakker K, Game FL, Hartemann-Heurtier A, Londahl M, Price PE, van Houtum WH, Jeffcoate WJ. A systematic review of the effectiveness of interventions to enhance the healing of chronic ulcers of the foot in diabetes. Diabetes Metab Res Rev. 2008 May-Jun;24 Suppl 1:S119-44. doi: 10.1002/dmrr.825.

Reference Type BACKGROUND
PMID: 18442185 (View on PubMed)

Gary Sibbald R, Woo KY. The biology of chronic foot ulcers in persons with diabetes. Diabetes Metab Res Rev. 2008 May-Jun;24 Suppl 1:S25-30. doi: 10.1002/dmrr.847.

Reference Type BACKGROUND
PMID: 18442179 (View on PubMed)

Jorgensen 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.

Reference Type BACKGROUND
PMID: 24111834 (View on PubMed)

Vogel TR, Petroski GF, Kruse RL. Impact of amputation level and comorbidities on functional status of nursing home residents after lower extremity amputation. J Vasc Surg. 2014 May;59(5):1323-30.e1. doi: 10.1016/j.jvs.2013.11.076. Epub 2014 Jan 7.

Reference Type BACKGROUND
PMID: 24406089 (View on PubMed)

McDonald S, Sharpe L, Blaszczynski A. The psychosocial impact associated with diabetes-related amputation. Diabet Med. 2014 Nov;31(11):1424-30. doi: 10.1111/dme.12474. Epub 2014 May 24.

Reference Type BACKGROUND
PMID: 24766143 (View on PubMed)

Jeffcoate WJ, Harding KG. Diabetic foot ulcers. Lancet. 2003 May 3;361(9368):1545-51. doi: 10.1016/S0140-6736(03)13169-8.

Reference Type BACKGROUND
PMID: 12737879 (View on PubMed)

Pence BD, Woods JA. Exercise, Obesity, and Cutaneous Wound Healing: Evidence from Rodent and Human Studies. Adv Wound Care (New Rochelle). 2014 Jan 1;3(1):71-79. doi: 10.1089/wound.2012.0377.

Reference Type BACKGROUND
PMID: 24761347 (View on PubMed)

Rasmussen BSB, Yderstraede KB, Carstensen B, Skov O, Beck-Nielsen H. Substantial reduction in the number of amputations among patients with diabetes: a cohort study over 16 years. Diabetologia. 2016 Jan;59(1):121-129. doi: 10.1007/s00125-015-3781-7. Epub 2015 Nov 22.

Reference Type BACKGROUND
PMID: 26590707 (View on PubMed)

Hellsten Y, Rufener N, Nielsen JJ, Hoier B, Krustrup P, Bangsbo J. Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2008 Mar;294(3):R975-82. doi: 10.1152/ajpregu.00677.2007. Epub 2007 Dec 19.

Reference Type BACKGROUND
PMID: 18094062 (View on PubMed)

Hoier B, Rufener N, Bojsen-Moller J, Bangsbo J, Hellsten Y. The effect of passive movement training on angiogenic factors and capillary growth in human skeletal muscle. J Physiol. 2010 Oct 1;588(Pt 19):3833-45. doi: 10.1113/jphysiol.2010.190439.

Reference Type BACKGROUND
PMID: 20693292 (View on PubMed)

Other Identifiers

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H-15008102

Identifier Type: -

Identifier Source: org_study_id

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