Lower limb complications are a substantial matter in the diabetic population and studies on the annual incidence of foot ulcers ranges from 1,0-4,1% while the cumulative lifetime incidence is approximately 15%. Foot ulcers may become complicated by infection or gangrene, and ultimately result in amputation. In addition foot ulcers have a significant impact on quality of life (QoL). The treatment of diabetic foot ulcers have not made substantial progress the latest years with regards to improved healing although there have been several actions taken to influate the process. The current practice consists of wound debridement, treatment of underlying infections and pressure reliefs. This trial investigates the adjunctive effects of high (80 mg) or low (10 mg) dose atorvastatin to conventional treatment on the healing of diabetic foot ulcers.

Condition	Intervention	Phase
Diabetes Mellitus Foot Ulcer	Drug: Atorvastatin (drug), 10 mg  Drug: Atorvastatin (drug), 80 mg	Phase II

Further Study Details: 

Primary Outcomes: To assess the efficacy of atorvastatin in patients with foot ulcers and type 1 or type 2 diabetes mellitus receiving conventional foot ulcer treatment in improving foot ulcer treatment with regards to:; 1. Number of ulcers completely healed within 12 weeks; 2. Time to complete healing (during 26 weeks of study); 3. Recurrence rates of foot ulcers (during 26 weeks of study); 4. Rate of reduction in wound size assessed at week 12 and week 26
Secondary Outcomes: To assess the efficacy of atorvastatin in patients with foot ulcers and type 1 or type 2 diabetes mellitus receiving conventional foot ulcer treatment in improving; 1. Lipid variables and micro-crp; 2. Tissue oxygenation assessed by measurements of transcutaneous oxygen tension proximally, perilesional and distally of the foot ulcer; 3. Systolic toe pressure; 4. Inflammatory markers (IL-6, TNF-alpha); 5. Other markers (BNP and advanced glycosilation end products (AGE))
Expected Total Enrollment:  20

The diabetic foot ulcers etiology are multiplex and the wound healing are often not very successful due to various reasons. The ulcer’s etiology are associated with peripheral vascular disease, autonomic neuropathy and endothelial. There may also be present some metabolic conditions that are not optimally for wound-healing delaying the process even more (hyperglycemia, hyperlipidemia, hyperinsulinemia, pro-coagulative state).

It has been shown that statins may improve these aspects making the use of this as adjuvant therapy in treating diabetic foot ulcers an interesting theory. There are so far not any direct evidence for this, although documentation exists for several other possible associated conditions.

This study aims to elucidate the pleiotropic effects of atorvastatin on the healing of diabetic foot ulcers.

Material and methods:

This 26-week prospective randomised, open, study will be conducted as a pilot to assess the efficacy of atorvastatin in improving diabetic foot-ulcer healing. Atorvastatin will be given in two dosages (10 mg and 80 mg) and evaluations between these groups will be done with regards to improvement in foot ulcer healing, microcirculation and inflammatory markers.

We aim to include 24 patients with diabetes (both type 1 and 2), over the age of 30, of both genders whom have a wound duration of less than 3 months. The patients will be recruited from the diabetic out-patient clinics in two centers (Gjøvik Hospital and Asker and Baerum Hospital).

Study plan:

We plan to begin the enrolment of eligible patients in autumn 2004. We plan for a 6 months inclusion period and hope to conclude this pilot study by autumn 2005. Results from the study will be presented in international papers or meetings concerning diabetes and complications.

Ages Eligible for Study:  30 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Provision of a written informed consent at the enrolment visit
• Men or women with age above 30 years
• Fertile women needs to take contraceptives or has to be sterilised
• Diagnosed with any diabetes mellitus type 1 or type 2
• Present foot ulcer with an ulcer duration <= 3 months

Exclusion Criteria:

• Intolerance to statins at any time in the past.
• Unwillingness to participate
• A history of alcohol or drug abuse within the last 2 years
• Foot ulcer with the etiology from vasculitis, pyoderma gangrenosum, angiodermatitis necroticans (hypertensive ulcer), necrobiosis lipoidica, hydrostatic pressure/venous insufficiency or any neoplasms (basalioma, kaposis sarcoma, squamous cell carcinoma etc).
• History of drug-induced hepatitis or previous liver enzyme elevations (> 3 times the upper limit of normal) while taking statins.
• History of drug-induced creatine phosphokinase (CPK) > 3 times the upper limit of normal.
• Critical limb ischemia that requires re-vascularisation procedures within 2 months
• Brachial-ankle index < 0,5
• Other serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the patient’s safety or successful participation in the trial.
• Any clinically significant abnormality identified on the enrolment medical history, physical examination, laboratory test which in the judgement of the investigator would preclude safe completion of the study.
• Active liver disease or hepatic dysfunction defined as ALAT or ASAT elevations > 2 times the upper limit of normal or total bilirubin > 1,5 times the upper limit of normal.
• Pregnancy

Please refer to this study by ClinicalTrials.gov identifier  NCT00134550

Odd E Johansen, MD      67809400  Ext. 0047    odd.erik.johansen@broadpark.no

Norway
      Asker and Baerum Hospital, Rud,  1309,  Norway; Recruiting
      Innlandet Hospital, Gjøvik, Gjøvik,  2819,  Norway; Not yet recruiting

Study chairs or principal investigators

Odd E Johansen, MD,  Study Chair,  Asker and Baerum Hospital   

Study ID Numbers:  The IDUS trial
Last Updated:  August 24, 2005
Record first received:  August 23, 2005
ClinicalTrials.gov Identifier:  NCT00134550
Health Authority: Norway: Norwegian Medicines Agency
ClinicalTrials.gov processed this record on 2005-08-30