Treatment of Ulcers Associated With Hammer, Mallet and Claw Toe Deformities in the Diabetic Patient Setting
Phase: NA
Conditions: Diabetic Foot Ulcer, Hammer Toe, Mallet Toe, Claw Toe
Sponsor: Steno Diabetes Center Copenhagen

 
 
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Version 2.2 13/03-2019 
 
 
Treatment of ulcers associated with hammer, mallet and claw toe deformities in the diabetic 
patient setting 
 
 
 
 
 
Trial/Study personnel and contact details 
 
 
Contact name 
 
 
 
Jonas Hedegaard Andersen, MD 
Steno Diabetes Center Copenhagen 
 
 
 
Niels Steensens Vej 2, 2820 Gentofte 
& 
North Zealand Hospital Hillerød Hospital 
Dyrehavevej 29 3400 Hillerød 
 
 
 
 
 
Primary investigator  
Jonas Hedegaard Andersen, MD 
Steno Diabetes Center Copenhagen 
 
 
 
Niels Steensens Vej 2, 2820 Gentofte 
& 
North Zealand Hospital Hillerød Hospital 
Dyrehavevej 29 3400 Hillerød 
 
Clinically responsible 
 
 
 
Peter Rossing, Professor MD  
Head of Complications Research                   
 
Steno Diabetes Center Copenhagen 
 
 
 
Niels Steensens Vej 2, 2820 Gentofte 
 
 
 
University of Copenhagen 
Denmark 
 
Investigators 
Marie Frimodt-Møller, MD Ph.d. 
Steno Diabetes Center Copenhagen 
 
 
 
Niels Steensens Vej 2, 2820 Gentofte 
 
 
 
 
Susanne Engberg, MD Ph.d. 
Steno Diabetes Center Copenhagen 
 
 
 
Niels Steensens Vej 2, 2820 Gentofte 
 
 
 
 
Klaus Kirketerp-Møller, MD. 

 
 
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Bispebjerg Hospital 
 
 
 
Bispebjerg Bakke 23, 2400 Copenhagen NV 
 
 
 
& 
 
 
 
Steno Diabetes Center Copenhagen 
 
 
 
Niels Steensens Vej 2, 2820 Gentofte 
 
 
 
 
Anne M. Rasmussen, Podiatrist MAH 
 
 
 
Steno Diabetes Center Copenhagen 
 
 
 
Niels Steensens Vej 2, 2820 Gentofte 
 
Participating Centers 
 
 
 
North Zealand Hospital Hillerød Hospital 
Dyrehavevej 29 3400 Hillerød 
 
 
 
 
Steno Diabetes Center Copenhagen 
 
 
 
Niels Steensens Vej 2, 2820 Gentofte 
 
 
 
 
Bispebjerg Hospital 
 
 
 
Bispebjerg Bakke 23, 2400 Copenhagen NV 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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1. STUDY RATIONAL 
Diabetes is one of the largest medical challenges facing the world today. 12% of the world’s health 
budget is spent on diabetes, which is USD 673 billion (Euros 585 billion). It is estimated that a lower 
limb is amputated due to diabetes every 30 sec. on a global scale, and its known that 85% of all 
amputations are performed due to a diabetic ulcer1.  In Denmark 320.000 citizens has a diabetes 
diagnosis, an additional 200.000 are estimated to have diabetes unknowingly, and 750.000 to have 
the pre-stages of diabetes2. These numbers have doubled in the past ten years and are estimated to 
cost DKK 86 million a day (or Euros 11.6 million a day)1. One of the complications to diabetes is the 
“diabetic foot syndrome”, which is a result of neurological abnormalities, vascular complications or 
a combination of the two. Knowledge about the causes of the disease has been gathered since the late 
nineteenth century3. In recent years, preventive therapy has been the focus of treatment, resulting in 
several national and international guidelines4,5,6. Focus has been on education in self-care and 
awareness of risk factors, combined with “Foot-at-Risk” evaluation7, at least once a year and off-
loading therapy crafted and applied by specialized personnel3,4.  
 
Steno Diabetes Center Copenhagen, University of Copenhagen, Denmark is a highly-specialized 
treatment facility focusing on the patient with diabetes. In spite of optimized treatment for patients 
with diabetes, and the fact that incidence of first time ulcers in patients with type 1 and 2 diabetes is 
declining, the incidence of first time ulcers is still 2.6 and 8.7  per. 1000 patient years for type 1 and 
2, respectively8. Diabetic foot ulcers have a known association with increased mortality, morbidity 
and economic burden9,10,11, at the same time most amputations in patients with diabetes are preceded 
by an ulcer12.  
 
Hammer, mallet and claw-toe deformities are some of the most common deformities associated with 
the diabetic foot syndrome. Prevalence has been reported between 32% and 46%13,14. These 
deformities are predictors of diabetic foot ulcers15,16. There are several theories on the etiology of 
hammer, mallet and claw toe deformities – the three classic deformities of the toes. In the diabetic 
patient setting, the classical theory is based on neuropathy (nerve damage associated with diabetes 
and other diseases), resulting in intrinsic muscle (muscles of the foot) dysfunction, changes that lead 
to imbalance between the flexor and extensor tendons, which in turn leads to hyperextension of the 
metatarsophalangeal (MTP) joint and/or flexion in the interphalangeal joints (IP), leading to the three 
classic deformities of the toes. The neuropathic theory is not sufficient to explain the full scope of the 

 
 
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problem, and other theories have been proposed17. In the non-diabetic patient, the neuropathic 
explanation is not viable, but the explanations still center on an imbalance between in- and extrinsic 
musculature, resulting from deformities in the foot either as flexor-substitution or stabilization 
deformities18. The deformities change the pressure on the plantar aspect of the foot19. These changes 
in pressure make specific contact point’s predilection sites for ulcers. The sites have been described 
as tip of the toe ulcers, cock-up ulcers, kissing ulcers and plantar metatarsal ulcers20, these sites will 
be referred to as ulcers associated with hammer, mallet and claw toe deformities, and are defined as 
cock-up ulcers that are placed at the dorsal side of proximal phalangeal joint of toes 2-5 and inter 
phalangeal joint of the hallux. A tip of the toe ulcer is placed at the pulpa of the affected toe. 
Metatarsal ulcers are placed at the plantar aspect of the distal head of the metatarsal bone of the 
involved toe. Kissing ulcers, which are placed between toes, and is due to pressure from the deformed 
toe/toes.  
 
The treatment of hammer, mallet and claw toe deformities in diabetes has classically consisted of 
offloading in the form of shoes, insoles and/or orthosis (i.e. silicone spacers, felt pads etc.) or flexor 
tendon tenotomy (cutting tendons) done by scalpel. Several studies on flexor tenotomies performed 
with scalpel have been performed21,22; all have reported acceptable or positive results on ulcer healing 
and low complication rates, including one study from our own institute23. At Diabetic Foot Study 
Group 2018 we presented unpublished results from a study showing that tenotomy done by needle 
has comparable results to the classical scalpel. However, no study has, to our knowledge, been 
published comparing conservative treatment with surgical approach to these deformities, let alone 
randomized controlled trials (RCT). At the same time no studies have, to our knowledge, looked at 
the effect on plantar pressure (pressure profile of the foot) and balance post flexor tenotomy in the 
above-mentioned setting. 
 
 
 
 
 
 
 
 

 
 
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2. WHAT DOES THIS TRIAL ADD TO CURRENT KNOWLEDGE?  
This is to our knowledge the first RCT looking at flexor tenotomies compared to conservative 
treatment. At the same time this is the first study looking at needle flexor tenotomies, as opposed to 
the classic tenotomies done by scalpel. The effect of flexor tenotomy on the balance of patients with 
diabetes has not been described earlier. 
 
 
3. HYPOTHESIS 
We hypothesize that treating ulcers associated with hammer, mallet and claw toe deformities in 
patients with type 1 and 2 diabetes with needle tenotomy is a safe and effective treatment, and superior 
to offloading (conservative) treatment done by silicon spacer, insoles, felt, and/or therapeutic sandals.  
I addition we hypothesize that needle tenotomy performed as a treatment for ulcers associated with 
hammer, mallet and claw toe deformities in patients with type 1 and 2 diabetes will not affect the 
patients balance or gait significantly. 
 
 
4. AIM 
This study is a randomized controlled trial (RCT). 
 
The aim of the RCT is to evaluate the effect of needle tenotomy when treating hammer, mallet and 
claw toe deformities and an associated ulcer in patients with diabetes.  
 
The study is designed as a prospective RCT comparing needle tenotomy with conservative treatment, 
for patients with deformities and active ulcers associated with the three deformities. 
Primary endpoint will be time-to-heal for patients with ulcers.  
Secondary endpoints will be effect on plantar pressure profile and balance (Rambling and trembling), 
new ulcers and the following complications: infections (defined as ailment associated with procedure 
or ulcer, that is diagnosed as infection by attending health professional), transfer lesions (defined as 
impending ulcers or actual ulcers at anatomical sites associated with hammer, mallet and claw toes 
in patients with diabetes, on non-treated hammer, mallet and claw toes after surgical treatment), minor 
amputations (defined as amputations below ankle level), major amputations (defined as amputations 
at or above ankle level), recurrence of a treated ulcer and incidence of new ulcers (defined as new 

 
 
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ulcer at anatomical location different from treated ulcer, and associated with hammer, mallet and claw 
toe deformities in patients with diabetes, on treated toes).  
 
 
5. STUDY I 
5.1 Design 
A prospective RCT involving patients with diabetes as well as one of the three deformities and an 
active ulcer associated with the mentioned deformities. By randomization, patients will be allocated 
to either conservative treatment or tenotomy performed by needle. 
 
5.2 Patients 
Note 
Patients who don’t meet the additional inclusion and exclusion criteria for gait and balance will be 
excluded from gait and balance but not the rest of the study. Conversely patients who don’t meet 
inclusion and exclusion criteria other than those additional for gait and balance will not be eligible 
for enrollment in any part of the study.   
 
Inclusion criteria 
• Patients aged 18 years or above 
• Type 1 or 2 diabetes 
• Hammer, mallet or claw toe deformity as judged by investigator 
• Ulcer associated with above mentioned deformities 
• Able to understand written and oral information 
• Ability to follow planned visits and treatment 
• Able to provide informed consent in Danish and/or English 
 
 
 
 
Additional Inclusion criteria for gait and balance 
• Able to complete the full schedule of visits in study II, and sub-study 

 
 
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• Able to perform gait and balance examination, as judged by 
investigator 
 
Exclusion criteria  
• Revascularization procedure in the affected limb planned, or 
undertaken within the 4 weeks prior to screening 
• Hammer, claw and mallet toe that are completely rigid in both MTP 
and IP joints 
• Toe blood pressure < 30mmHg 
• Infections of the foot ulcer needing surgical treatment 
• Prior major amputations on affected or ipsilateral leg 
• Other corrective operation is indicated to treat patients foot 
deformities as deemed by investigator 
• Current treatment with cytotoxic drugs or with systemically 
administered glucocorticoids 
• Treatment of foot ulcers with growth factors, stem cells or equivalent 
preparations within the 8 weeks prior to screening  
• Likely inability to comply with the need for planned visits because of 
planned activity 
• Participation in another interventional clinical foot ulcer-healing trial 
within the 4 weeks prior to screening 
• Prior enrolment in this trial 
• Judgement by the investigator that the patient does not have the 
capacity to understand the study procedures or provide written 
informed consent 
 
Additional exclusion criteria for gait and balance  
• New ailments incurred by patient between gait and balance 
analysis before tenotomy and 3 months post tenotomy including 
but not limited to cerebral insult, fractures with influence on gait 
and/or balance, new medications with effect on gait or balance,  

 
 
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neurological diseases with effect on gait and/or balance. 
Individual cases will be reviewed at investigators discretion. 
 
Discontinuation of patients 
• Patient discontinues assigned treatment for any reason, while not 
fulfilling one of the studies accepted endpoints 
• Patient incurs a serious adverse event (SAE), defined as death or 
sepsis related to the study procedure 
• Investigator decides to discontinue patient due to health or compliance 
reasons 
• Patient misses 3 consecutive visits 
• Patient misses 5 or more visits during the full treatment period 
Patients who discontinue the study early will be invited to have a clinical visit before being 
discontinued. 
Patients that are discontinued will revert to their normal treatment plan, and continue in their 
respective clinics. 
 
Endpoints 
• Ulcer healed (ulcer is healed when complete reepithelization is 
attained) 
o When/if ulcer is healed pictures will be send to two external 
evaluators for confirmation  
• Ulcer not healed at follow-up week 10 
• Patient incurs minor or major amputation on either treated or non-
treated limb 
• Patient receives surgical intervention relevant to the study (other than 
planned in study) 
• Patient incurs infection associated with study (as deemed by 
investigator) requiring surgery or admission to hospital. 
Additional Endpoint for gait and balance 

 
 
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• Patient incurs new ailment between gait and balance analysis before 
tenotomy and 3 months post tenotomy including but not limited to 
cerebral insult, fractures with influence on gait and/or balance, new 
medications with effect on gait or balance, neurological diseases with 
effect on gait and/or balance. Individual cases will be reviewed at 
investigators discretion. 
 
5.3   Method 
Patients that meet the inclusion and exclusion criteria will be randomized to either  
 
A: Intervention 
 
Needle-tenotomy  
 
 
 
Offloading treatment 
 
B: Conservative Treatment 
 
Offloading treatment  
 
Both groups will be offered offloading treatment in the form of therapeutic sandals with 
individualized insoles and standard wound care and bandage changes.  
Both groups will be offered a gait and balance examination. The gait and balance examination will 
be performed before visit day 0, and 3 months post first gait and balance examination. 
 
5.3.1  Needle Tenotomy Procedure 
Patient is placed in seated posture with feet elevated. The toe(s) with hammer, mallet or claw toe 
deformity is anesthetized by a digital toe block with 1-5 ml of 1% lidocaine administered for each 
toe. The toe digital block is administered through a plantar approach, at the web level of the 
deformed toe(s), with a 0,6 mm diameter and 30mm long needle.  
After anesthetizing the toe(s) the plantar aspect of the toe at web level is disinfected with an alcohol 
based disinfectant twice. 

 
 
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Both the long and short flexors are then severed with a 1.2mm diameter and 40mm long needle 
through a plantar approach, immediately proximal to the web level of the toe. 
After the procedure a dry gauze bandage is applied and the patients treated foot/feet is/are elevated 
for 30 minutes to achieve haemostasis, and the bandage is checked for bleeding before discharge. 
 
5.3.2  Offloading Treatment 
Offloading Treatment: The patient’s ulcer and deformity are offloaded by treatment with one or a 
combination of the following treatments: 
▪ Therapeutic sandals with rocker-bottom and individual insoles 
▪ Silicone device 
▪ Handmade shoes with rocker-bottom and individual insoles 
▪ Air-cast Walker 
▪ Felt pad 
▪ Capsule 
▪ Own shoes and individual insoles 
 
5.3.3  Standard care and bandage changes 
Standard care includes: 
• Ulcer debridement done by scalpel, scissors, curette, forceps and ronguers. Ulcer 
debridement includes surgical removal of dead tissue like necrotic tissue, infectious tissue, 
fibrinous and necrotic bone tissue. The necessary extent of debridement is evaluated by the 
treating physician. 
•  Debridement of callus with scalpel, curette, scissor or forceps. Debridement of callus 
consists of surgical removal of callus on feet. The necessary extent of debridement is 
evaluated by the treating physician.  
• Irrigation of wound with tap-water or sterile saline 
 
 
Bandage changes includes 
• Choice of any bandage that is deemed optimal for the wound by treating physician, with 
exception of bandages with growth factors and stem cells or comparable compounds. 

 
 
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• Treatment with compression bandages or stockings as deemed relevant by treating physician 
  
5.3.4  Gait and balance analysis 
Both gait and balance analysis is performed at Hvidovre Hospital at Human Movement Analysis 
Laboratory. The gait analysis is performed using a biomechanical pressure plate (Emed, Novel, 
Munchen, Germany). Patients will be asked to walk at normal speed back and forth over the pressure 
plate. The procedure is repeated until patient strikes the plate in correct manner. At the same time a 
digital camera lining the pressure plate filming position of patients feet during gait. In this manner a 
dynamic picture of pressure at different parts of the foot is registered. The procedure is a normally 
used clinical examination used for patients with diabetes, and has been used in prior approved studies 
(H-A-2008-112). The data is processed using novel scientific software. 
The balance analysis will be performed using the AMTI forceplate model OR6-7(AMTI, Watertown, 
MA, USA). Patients will be asked to stand on biomechanical forceplate, where they are asked to stand 
as still as possible with feet parted by standard block for 30 seconds. Procedure will be completed 3 
times with open eyes.  Feet centering pressure and movement is registered for the 30 seconds. Data 
is collected using Nexus 2.8.1 (vicon Motion Systems Ltd. Oxford, UK) and processed using Matlab 
(Natick, MA, USA). Data collected yields a measurement of patients postural control and balance. 
The method has been approved for prior studies (KF 02 323948 and H-A-2008-112).   
 
 
 
 
 
 
 
 
 
 
 
 
 
5.4 Visit-plan 

 
 
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Patients in both the intervention and conservative groups will be expected to adhere to a specified 
visit-plan  
Visit-plan 
Inclusion Day 0 
Day 7 
Later 
Visit1 
End2 
Follow-
up3 
Duration 
2 hours 
30 
min 
30 
min 
30 min 
30 
min 
30 min 
In/exclusion criteria 
+ 
 
 
 
 
 
Baseline blood samples and physical 
exam 
+ 
 
 
 
 
 
Patient history 
+ 
 
 
 
 
 
Foot Examination 
+ 
+ 
+ 
+ 
+ 
+ 
Changes in Medicine/ new ailments 
 
+ 
+ 
+ 
+ 
 
Ulcer Photo 
+ 
+ 
+ 
+ 
+ 
+ 
Toe systolic blood pressure (TSB) 
Ankle/brachial pressure index (ABPI) 
+ 
 
 
 
 
 
Neurological assessment  
+ 
 
 
 
 
 
Randomization 
+ 
 
 
 
Tenotomy/silicone spacer application4 
+ 
 
 
Standard-Care & Offloading 
+ 
+ 
+ 
+ 
+ 
+ 
Ulcer evaluation 
+ 
+ 
+ 
+ 
+ 
+ 
Footwear assessment 
 
+ 
+ 
+ 
+ 
+ 
1: Later visits are performed every 14 days (until week 10, where there will only be 1 week between 
week 9 and week 10 visits) 
2: This visit only happens if patient incurs on of the named endpoints  

 
 
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3: Follow-up visits are performed at 3, 6 and 12 months 
4: Depending on allocated treatment via randomization 
 
5.5 Detailed description of visits 
The following section describes all visits in the study.  All visits will be conducted by trained 
scientific staff, under responsibility of site investigator, and according to the delegation log. 
Procedures included in the visits will be conducted according to standard operating protocol (SOP) 
and manual of operations (MOP). It is the responsibility of principal investigator to train scientific 
staff in SOP and MOP. And to ensure that relevant SOP and MOP are available for the study 
personnel before procedures are performed.  
 
The time between inclusion and visit 0 should be at least 14 days, to allow for time to do gait and 
balance analysis at Hvidovre Sygehus 
  
5.5.1 Inclusion 
Inclusion visit can only take place when written consent form is signed by patient, and filed in patient 
log.  
The following procedures will be performed: 
• In/exclusion criteria ( see section 5.2) 
• Baseline blood samples including: 
o Hemoglobin A1C  
o Creatinine 
o Estimated glomerular filtration rate 
o Hemoglobin 
o Albumin 
o International normalized ratio 
o Low-density lipoproteins 
o Leucocytes 
o C-reactive protein 
o All blood samples are analyzed immediately, and nothing is preserved in biobank. The 
total amount of blood is evaluated to be less than 50ml pr. patient.  
 

 
 
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• Baseline physical examination including measurements of: 
o Blood pressure 
o Heart rate 
o Oxygen Saturation 
o Heart and pulmonary auscultation  
o Electro Cardiogram  
o Height 
o Weight 
• Patient history including information on: 
o Gender  
▪ male or female 
o Ethnicity 
o Diabetes type  
▪  1 or 2 
o Duration of diabetes  
▪ measured in years with no decimal 
o Duration of foot ulcer  
▪ measured in days 
o Competing diseases/comorbidity  
▪ By diagnosis and year of debut 
o Current medicine  
▪ quantity and type 
o Smoking  
▪ quantity and nature, present or past 
o Alcohol intake  
▪ quantity   
o Height, weight and BMI 
▪ In m(two decimals), kg(one decimal) and kg/m2(one decimal) 
o Prior surgery on feet 
▪ Type and year 
o Prior ulcers of feet/legs 
▪ Location and year 

 
 
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o Prior amputations 
▪ Location, type and year 
o Prior/current history of Charcot’s ailment 
▪ Debut year 
▪ Activity 
o Retinopathy 
▪ Simplex, proliferative and/or laser treated 
o Urinary albumin excretion rate 
▪ Normal, micro-, macro- or prior albuminuria 
o Peripheral neuropathy 
▪ Yes/no 
▪ Pain associated with? 
o Prior offloading therapy 
▪ Type 
o Relationship status 
▪ Married yes/no and/or living with partner yes/no 
• Foot examination 
o Inspection of pressure point, and deformities 
o Pulses 
o Deformities 
• Ulcer Photo 
o Photos of affected foot are taken from two angles and uploaded to healthcare IT system 
used at the participating institutes (Sundhedsplatformen) 
• TSBP and ABPI 
o TSBP and ABPI are performed by educated staff and results evaluated 
o Patients with TSB under 30 mmHg are referred to department of vascular surgery 
where deemed necessary 
• Neurological assessment 
o Biothesiometry tests are performed by educated staff 
o Monofilament testing is performed by educated staff 
o Neuropathy symptoms are examined and registered 
• Randomization 

 
 
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o Randomization is performed in RedCAP 
• Standard care & offloading 
o See section 5.3.2 and 5.3.3  
• Ulcer evaluation 
o Assessment of ulcer surroundings 
o Assessment of infection 
o Assessment of healing 
o Measurement of longest length, width and depth in mm 
o Measurement of area in mm3(length*width*depth) 
o Categorizing by Texas Grading System 
o Categorizing by diagnosis related group system 
 
 
 
5.5.2 Visit Day 0 
Visit day 0 can only be performed when patient has attended Gait and Balance visit 1, dependent on 
patient eligibility for enrollment in gait and balance examination. If patient isn’t eligible for gait and 
balance examination but eligible for the rest of the study visit day 0 can be performed as soon as 
possible after inclusion visit 
• Foot examination 
o Inspection of pressure point, and deformities 
o Pulses 
o Deformities 
o New Ulcers 
• Ulcer Photo 
o Photos of affected foot is taken from two angles and uploaded to healthcare IT system 
used at the participating institutes (Sundhedsplatformen) 
• Tenotomy/conservative treatment application 
o The allocated treatment is performed 
o For details on tenotomy see section 5.3.1  
o For details on conservative treatment see section 5.3.2 
• Standard care & offloading 

 
 
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o See section 5.3.2 and 5.3.3  
• Ulcer evaluation 
o Assessment of ulcer surroundings 
o Assessment of infection 
o Assessment of healing 
• Measurement of longest length, width and depth in mm 
• Measurement of area in mm3(length*width*depth) 
o Assessment of incision site (where applicable) 
o Measurement of length, width and depth of ulcer(s) after debridement 
• Categorizing by Texas Grading System 
• Footwear assessment 
o Footwear and/or current offloading is evaluated 
o All patients in conservative and treatment group will be offered therapeutic sandals 
with customized insole at this visit 
• Changes in medicine/new ailments 
o Changes to the patient’s medicine, and/or new diagnosis are registered 
 
 
5.5.3 Visit Day 7, 14, later visit (until week 10) 
The following is a specification of the above mentioned visits. If at any visit, before week 10, the 
ulcer is deemed healed or patient reaches week 10 without attaining ulcer healing patients are planned 
for end visit.  
 
• Foot examination 
o Inspection of pressure point, and deformities 
o Pulses 
o Deformities 
o New Ulcers 
• Changes in medicine/new ailments 
o Changes to the patient’s medicine, and/or new diagnosis are registered 
• Ulcer Photo 

 
 
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o Photos of affected foot is taken from two angles and uploaded to healthcare IT system 
used at the participating institutes (Sundhedsplatformen) 
• Standard care & offloading 
o See section 5.3.2 and 5.3.3  
• Ulcer evaluation (if relevant) 
o Assessment of ulcer surroundings 
o Assessment of infection 
o Assessment of healing 
• Measurement of longest length, width and depth in mm 
• Measurement of area in mm3(length*width*depth) 
o Assessment of incision site (where applicable) 
o Measurement of length, width and depth of ulcer(s) after debridement 
• Categorizing by Texas Grading System 
• Footwear assessment 
o Footwear and/or current offloading is evaluated 
• Complications 
o Complications associated with tenotomy is registered (if relevant) 
o SAE is registered (if relevant) 
 
 
 
 
5.5.4 End 
End visit is only performed if patients treated ulcer is healed, or treated ulcer has not healed at week 
10 visit.  
•  Foot examination 
o Inspection of pressure point, and deformities 
o Pulses 
o Deformities 
o New Ulcers 

 
 
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o Ulcer recurrence (If treated ulcer(s) is/are deemed as healed at earlier visits, but recur 
at same anatomical location at later visit) 
• Changes in medicine/new ailments 
o Changes to the patient’s medicine, and/or new diagnosis are registered 
• Ulcer Photo (if relevant) 
o Photos of affected foot are taken from two angles and uploaded to healthcare IT system 
used at the participating institutes (Sundhedsplatformen) 
• Standard care & offloading 
o See section 5.3.2 and 5.3.3  
• Ulcer evaluation(if relevant) 
o Assessment of ulcer surroundings 
o Assessment of infection 
o Assessment of healing 
o Measurement of longest length, width and depth in mm 
o Measurement of area in mm3(length*width*depth) 
o Assessment of incision site (where applicable) 
o Measurement of length, width and depth of ulcer(s) after debridement 
o Categorizing by Texas Grading System 
• Footwear assessment 
o Footwear and/or current offloading is evaluated 
• Complications 
o Complications associated with tenotomy is registered (if relevant) 
o SAE is registered (if relevant) 
 
 
 
 
5.5.5 Follow up 
The following is a specification follow up visits. Performed at 3, 6 and 12 months post day 0 visit  
 
• Foot examination 
o Inspection of pressure point, and deformities 

 
 
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o Pulses 
o Deformities 
o New Ulcers 
• Changes in medicine/new ailments 
o Changes to the patient’s medicine, and/or new diagnosis are registered 
• Ulcer Photo 
o Photos of affected foot is taken from two angles and uploaded to healthcare IT system 
used at the participating institutes (Sundhedsplatformen) (If relevant) 
• Standard care & offloading 
o See section 5.3.2 and 5.3.3  
• Ulcer evaluation (if relevant) 
o Assessment of ulcer surroundings 
o Assessment of infection 
o Assessment of healing 
o Measurement of longest length, width and depth in mm 
o Measurement of area in mm3(length*width*depth) 
o Assessment of incision site (where applicable) 
o Categorizing by Texas Grading System 
• Recurrence of ulcer (if relevant) 
o Assessment of ulcer surroundings 
o Assessment of infection 
o Measurement of longest length, width and depth in mm 
o Measurement of area in mm3(length*width*depth) 
• Footwear assessment 
o Footwear and/or current offloading is evaluated 
• Complications 
o Complications associated with tenotomy is registered (if relevant) 
o SAE is registered (if relevant) 
 
5.5.5 Gait and Balance visit 1 
This visit will be performed before visit day 0 after inclusion visit at Hvidovre Hospital at Human 
Movement Analysis Laboratory. At the visit the following examinations will be performed 

 
 
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• Gait and balance examination (see section 5.3.4 for details) 
5.5.6 Gait and Balance visit 2 
This visit will be performed 3 months post gait and balance visit 1, at Hvidovre Hospital at Human 
Movement Analysis Laboratory. At the visit the following examinations will be performed 
• Gait and balance examination (see section 5.3.4 for details) 
 
5.6 Randomization 
• Will be done in an open source electronic data capturing system (REDCaP), using the REDCaP 
Randomization module. This is based on an allocation table which will be generated by a 
statistician at our institute, with no other connection to the study. 
• Patients will be block randomized, and stratified by treatment facility. Blocks will be of 5 patients 
each, stratified by study site.  
 
5.8 Statistics 
All statistical analysis will be performed using the version of SAS currently used at our institute. All 
data will be analyzed on the intention to treat basis. All baseline data will be presented using 
appropriate summarizing statistics. Appropriate comparable statistical analysis will be applied to 
 
• Mean time (in days) to healing of ulcers(s) in treated limb 
• Mean time (in days) to healing of incision sites 
• Incidence of minor amputations  
• Incidence of major amputations  
• Plantar pressure profile 
• Rambling and trembling 
Odds-ratio will be applied to 
• The incidence of secondary infection  
• Pain in treated limb, associated with tenotomy  
• Transfer lesion  
• Recurrence of ulcers on the treated limb  
• Incidence of new ulcers on feet  

 
 
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Sample-size 
The calculation is based on a Type 1 error rate () of 5%, and a power (1-) of 80%. The primary 
endpoint is time-to-heal of ulcer associated with hammer, mallet or claw toe deformity. The mean 
of the intervention group (A) is set at 4 weeks, which is the average time to healing we observed in 
a pilot study done on needle tenotomies at our institute24, while the mean of the control group(B) is 
set at 10 weeks, which has been reported by Zimny when evaluating diabetic foot ulcers treated 
with standard care25,26. However, time-to-heal, when looking at the diabetic foot ulcer, is dependent 
on multiple factors like size, etiology and patient co-morbidities, therefore the standard deviation 
()  is set at 10. The clinical minimal relevant difference (miredif) for time-to-heal is set at 6 weeks 
(B-A). 6 weeks shorter time-to-heal, is seen as clinically relevant difference, on based on clinical 
experience, and a goal of time to heal at 4 weeks compared to the above reported 10 week average 
healing time attained with standard care31,32.   
 
The calculator used is a 2 means, 2 sample, 2-sided equality calculator.  
nB=(1+1/κ) ((σ z1−α/2+z1−β)/(μA−μB))2 
nB= Sample size 
κ= The matching ratio 
 
With the above described parameters, the sample size is 44 patients, which due to an expected 
dropout of 10% will be extended to 50 patients. 
 
 
 
 
 
 
 
6. PERSPECTIVE 
The results of these studies will allow us to evaluate if there is a clinical advantage in performing 
tenotomies. Several studies have shown that tenotomies done by scalpel are safe and that most ulcers 

 
 
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23 
heal27,28, but none have compared tenotomies with standard care. Our hypothesis is that patients with 
ulcers associated with hammer, mallet and claw toe deformities will heal faster when treated by 
tenotomy. At the same time, unpublished data from our institute show that tenotomy done by needle 
has comparable results to tenotomy done by scalpel. If this minimal invasive procedure, that can 
easily be performed in an everyday clinical setting, can lead to significant reductions in healing times, 
there is a potential for significant reductions in socioeconomic costs. 
 
 
7. QUALITY CONTROL AND MONITORING 
The studies will be performed in accordance with the Helsinki Declaration, International Council for 
Harmonization of technical requirements for pharmaceuticals for human use (ICH) Guidelines for 
good Clinical Practice (GCP)29 and after approval by the The National Committee on Health Research 
Ethics and the Data Monitoring Board in Denmark. The study will be registered on 
http://www.clinicaltrials.gov/.  
 
Permission for a third person to have access to patient data will be obtained at screening visit. 
Investigators will provide access to source data and relevant documents in connection with 
monitoring, inspections, and audits to all relevant authorities. 
 
 
8. ETHICAL CONSIDERATIONS AND DATA SAFETY 
The study will be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki 1996 and the principles of GCP30 
 
8.1 Ethical committee approval 
The appropriate approval from a local Danish ethical committee will be obtained before start of trial, 
and their guidelines will be followed throughout the process. Patients will receive oral and written 
information on the study, before being required to sign an informed consent paper. 
 
8.2 Personal data usage and protection  
The appropriate approval from the Danish data protection agency in the Capital Region will be 
obtained before the study commences, and their guidelines will be followed throughout the process. 

 
 
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All patient data will be stored and treated in accordance with regulation 2016/679 from the 
European parliament on the protection of natural persons with regard to the processing of personal 
data and on the free movement of such data, dated 27 April 201631, and the Danish amendment to 
regulation 2016/67932.  
  
8.3 Patient Perspective and Conclusion 
Patients enrolled in this study will receive a treatment that is already implemented in our and several 
other clinics, and the unpublished data from our retrospective study and the formerly published data 
on tenotomies, points towards tenotomies being a safe and effective treatment of hammer, mallet and 
claw toes, with a low risk of complications for patients with diabetes. The enrolled patients will in 
addition receive a gait and balance analysis that can be used as a diagnostic tool to help in treatment 
generally. Patients who don’t receive intervention in the form of tenotomies in the study, will receive 
standard offloading and ulcer treatment, and be offered to undergo tenotomy after completing 10 
weeks observation in the study if relevant in addition they will be offered a gait and balance 
examination with mentioned benefits. In conclusion the patients enrolled in the study will receive a 
treatment with potential benefits for them, and a low risk of complications making the study ethically 
sound.   
 
 
 
 
 
 
 
 
 
 
 
 
9. BUDGET/ECONOMY 
 
10.1 Budget  

 
 
TODD II Protocol 
25 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All figures refer to DKK 
Consumables are not included, because they are present in clinic, and would be used regardless 
of patients’ participation in the study 
 
 
 
 
 
 
 
10.2 Economy 
The study is funded by Steno Diabetes Center Copenhagen, and two private funds namely Jascha 
fonden and Ejnar og Aase Danielsens Fond.  
Category 
Description 
Expenses 
Covered 
Salary 
Monthly 
salary 
for 
chief 
investigator 
(64,171.75 
monthly) 
for 36 months 
1,155,092 
Salary 
Salary for podiatrist 16 
hours a week (208 
DKK/hour) for 3 years 
(156 weeks)  
259,584 
External 
clinical 
testing 
Gait analysis before 
and after tenotomy for 
50 
patients 
(4000 
DKK/patient) 
200,000 
Publication 
Publication Fee  
15,000 
Total 
 
1,629,676 

 
 
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26 
• Aase og Ejnar Danielsens Fond-50,000 dkk 
• Jascha Fonden – 250,000 
• Steno Diabetes Center Copenhagen – 1,329,676 
There are no economic incentives for patients, but they will be offered refunding of travel expenses, 
in correlation with kilometers traveled.  
 
There are no economic incentives or potential winnings for treating health professionals.  
 
 
10. RECRUITMENT 
Patients will be recruited and treated at the three study sites, Bispebjerg Hospital, Hillerød Hospital 
and Steno Diabetes Center Copenhagen. Healthcare professionals (doctors, nurses and podiatrists) 
with daily care of patients with diabetes will be encouraged to look for potential study candidates in 
the outpatient clinics. If any potential candidates are found, patients will receive written information 
on the project, asked if we can contact them by telephone, and referred to one of the investigators for 
further screening. When referred to investigator, eligibility criteria will be confirmed based on 
information from the patients’ electronic record (sundhedsplatformen). Patients will hereafter be 
contacted by telephone. If patients do not respond to contact by telephone, they will be contacted by 
mail.  
 
In addition to the above mentioned method, primary investigator will conduct a screening of patients 
that are currently treated at the three institutes for eligible candidates. This screening will be 
conducted through transmission of data to the primary investigator from the patient electronic record 
(sundhedsplatformen) in accordance with paragraph 46 of the Danish health laws. The data that is 
transmitted and screened in patient electronic record, includes all data relevant for in/exclusion 
criteria, namely information on prior diagnoses, results of prior vascular investigations on toe blood 
pressure and ankle brachial index, information on prior operations through journal notes, prior 
treatments with specific medications i.e. prednisolone, chemotherapy etc., date of birth, ulcer 
diagnosis and ulcer cause through journal notes and diagnosis list. 
 
 

 
 
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27 
 Identified candidates will be contacted by letter. If patients do not respond to letter, they will be 
contacted by phone. 
 
 Before written consent is given, patients will be informed orally and in writing by the educated study 
personnel, including information on procedures, visits, goal of the study, and their rights as 
participants. 
 
General practitioners and licensed podiatrists in the region will be contacted by letter and asked to 
refer likely candidates to relevant study site (i.e. Hillerød, Bispebjerg or Steno). The letter will be a 
standard text  
 
Written consent will be acquired at inclusion visit by study related personnel. Patients will be 
required to fill out written consent form, after they have received oral and written information and 
been allowed up to 24 hours consideration and the possibility of bringing a personal assessor to 
participate at information and screening visits. If the patient needs additional time to consider, a 
follow-up meeting will be arranged minimum 24 hours after the first visit. Patients are informed 
that they can always withdraw their commitment to participate in the study, without consequences 
for their further treatment. No study related procedures are done until informed consent is signed by 
the patient. 
After written consent is given by patients, this will grant primary investigator and Steno Diabetes 
Center Copenhagen access to patients’ health information, including information in electronic 
records. This access will be used solely to evaluate patient health related data relevant to the 
research project.   
 
 
 
 
 
11. DISSEMINATION OF RESULTS 
The study is initiated by Peter Rossing. Data is owned by the investigators. Positive, inconclusive as 
well as negative study results will be published in both national and international oral and written 
presentations as well as peer-reviewed international scientific journals. If data against expectations 

 
 
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are not published in international journals, positive as well as negative study results will be 
published on a public website, for example www.clinicaltrials.gov. 
 
 
12. PATIENT INFORMATION 
13.1 Written Information 
All patients will receive information detailing the project, written information on their rights as   
Participants in research projects from the Danish ethics committee33, and written information on the 
procedure, potential unintended side effects, and what to expect after the operation.  
 
13.2 Verbal Information 
All patients will be informed in layman’s terms on the details of the operations, potential 
unintended side effects, and what to expect after the operation. 
 
 
1 Diabetic Foot International (http://www.d-foot.org/d-footinternational/) 
2 The Danish diabetes society (http://www.diabetes.dk/presse/diabetes-i-tal/diabetes-i-danmark.aspx) 
3 Some historical aspects of diabetic foot disease. (Connor 2008) 
4 NICE Guidelines on Diabetic Foot Problems prevention and management (2015) 
5 Prevention and management of foot problems in diabetes - IWGDF (2015) 
6 Increased healing in diabetic toe ulcers in a multidisciplinary foot clinic- An observational cohort study (Almdal 2015) 
7 Diabetic foot disease: From the evaluation of the “foot at risk” to the novel diabetic ulcer treatment modalities (Amin 
2016) 
8 Decreasing incidence of foot ulcer among patients with type 1 and type 2 diabetes in the period between 2001-2014 
(Rasmussen 2017) 
9 High prevalence of ischemia, infection and serious comorbidity in patients with diabetic foot disease in Europe. 
Baseline results from the Eurodiale study (Prompers 2006) 
10 Cost of treating diabetic foot ulcers in five different countries (Cavanagh 2012) 
11 Reoperation and Reamputation After Transmetatarsal Amputation  A Systematic Review and Meta-Analysis (Thorud 
2016) 
12 Peripheral vascular disease and diabetes. In: Diabetes in America: diabetes data compiled 1984. (Palumbo 1985)  
13  Prevalence of Radiographic Foot Abnormalities in Patients with Diabetes (Smith 1997) 
14 Prevalence of foot pathology and lower extremity complications in a diabetic outpatient clinic (Holewski 1989) 
15 Foot ulcer risk and location in relation to prospective clinical assessment of foot shape and mobility among persons 
with diabetes (Cowley 2008) 
16 A prospective study of risk factors for diabetic foot ulcer (Boyko 1999) 
17 Role of intrinsic muscle atrophy in the etiology of claw toe deformity in diabetic neuropathy may not be as 
straightforward as widely believed. (Bus 2009) 
18 McGlamrys comprehensive textbook of foot and ankle surgery 
19 Elevated plantar pressures in neuropathic diabetic patients with claw hammer toe deformity. (Bus 2005) 
20 Percutaneous Tenotomy for the Treatment of Diabetic Toe Ulcers (Tamir 2014) 
21 Percutaneous flexor tenotomy for treatment of neuropathic toe ulceration secondary to toe contracture in persons with 
diabetes- a systematic review. (Roukis 2009) 
22 Effectiveness of percutaneous flexor tenotomies for the management and prevention of recurrence of diabetic toe 
ulcers a systematic review (Scott 2016) 
                                                 

 
 
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23 Percutaneous flexor tenotomy for preventing and treating toe ulcers in people with diabetes mellitus (Rasmussen 
2013) 
24 Unpublished data from pilot study done at our institute 
25 Determinnants and estimation of healing time in diabetic foot ulcers (Zimny 2002) 
26 Healing times and predictions of wound healing in neuropathic diabetic foot ulcers a prospective study (Zimny 2005) 
27 Percutaneous flexor tenotomy for treatment of neuropathic toe ulceration secondary to toe contracture in persons with 
diabetes- a systematic review. (Roukis 2009) 
28 Effectiveness of percutaneous flexor tenotomies for the management and prevention of recurrence of diabetic toe 
ulcers a systematic review (Scott 2016) 
 
30 https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-
human-subjects/ 
 
32 https://www.retsinformation.dk/Forms/r0710.aspx?id=201319 
33 http://www.nvk.dk/forsoegsperson/dine-rettigheder-som-forsoegsperson