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HELP-Apheresis in Diabetic Ischemic Foot Treatment (H.A.D.I.F) (HADIF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2014 by Universita di Verona
Information provided by (Responsible Party):
Maria Grazia Zenti, Universita di Verona Identifier:
First received: January 22, 2012
Last updated: December 18, 2014
Last verified: December 2014

Diabetic foot (DF) is a common, severe and costly complication of diabetes. DF is underlied by neuropathy, atherosclerosis of distal arteries and infection, which result in tissue ulcers and necrosis. Alterations in microcirculatory function and in blood rheology may concur in causing tissue damage.

In recent years there has been accumulating evidence that LDL apheresis (LA) does not only reduce cholesterol but also has a series of pleiotropic effects that improve the microcirculation, increasing peripheral tissue perfusion.

HADIF is a randomized, multicentric, prospective clinical study aimed at assessing the effect of LDL apheresis treatment in association with traditional therapy for ulcers, in patients with an ischemic diabetic foot ulcer (class I and II Texas Wound Classification System)and peripheral vasculopathy not susceptible to revascularization. A total of 132 patients will be enrolled. Participants will be centrally randomized to receive traditional therapy alone (TT) or in association with LA. TT includes standard medication of ulcers, antiaggregant therapy and statins. LA will be performed with HELP system, for a total of 10 sessions in 9 weeks. The primary end-point of the study is ulcer healing; secondary endpoints include improvements of peripheral oxygenation, resolution of pain, reduction of circulating inflammatory markers, cardiovascular events during one year's follow-up.

This clinical Study has been approved by local EC on 25 may 2011 (Study number 1953).

TO BE NOTED: since diabetic patients in our "Diabetic-Foot UNIT" often presented foot ulcers more severe than class II Texas, a formal amendment has been submitted to EC for recruiting patients with diabetic foot ulcer of class III Texas. The amendment was already approved on 5 may 2012.

Condition Intervention
Foot Ulcers
Arteriosclerosis Obliterans
Diabetes Mellitus
Device: LDL-apheresis

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: HELP-Apheresis in Diabetic Ischemic Foot Treatment (H.A.D.I.F): a RCTrial to Evaluate the Effect of LDL-apheresis on the Recovery of Diabetic Ulcers in Patients With Peripheral Vasculopathy Not Susceptible to Revascularization.

Resource links provided by NLM:

Further study details as provided by Universita di Verona:

Primary Outcome Measures:
  • Proportion of subjects obtaining the ulcer healing (Class 0A according to TEXAS classification) after 12 month from the study starts. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Ulcer evaluation: staging according to Texas Wound classification System and ulcer evaluation (surface diameter, mapping of the lesions by means of drawing their profiles on Opsite film,and digital picture), at basal, at 9th week and after a 3-6-9-12 month follow-up.

Secondary Outcome Measures:
  • Improvement of the peripheral oxygenation evaluated by means of transcutaneous oximetry measurement at foot level: TcP O2 (mmHg). [ Time Frame: basal, at 4th and 9th week and after 3-6-9-12 month follow-up ] [ Designated as safety issue: No ]
  • Evaluation of pain level variation (verbal numeric range; score from 1 to 10) [ Time Frame: basal, at 4th and 9th week and after 3-6-9-12 month follow-up ] [ Designated as safety issue: No ]
  • Lowering of circulating inflammation markers (C Reactive Protein, Fibrinogen). CRP plasmatic concentration (mg/L) and fibrinogen (g/L) [ Time Frame: at the beginning of the study and respectively after 3 - 6 - 9 e 12 months. ] [ Designated as safety issue: No ]
  • Rate of cardiovascular events in the observation period (1-year follow-up). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • proportion of subjects with minor amputation (only toe or part of the foot removed)- in agreement with the approved amendment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • proportion of subjects with major amputation (these are usually below the knee or above the knee)- in agreement with the approved amendment [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 132
Study Start Date: February 2012
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDL-apheresis and TT

The patient of the experimental Arm, in addition to Traditional Therapy (TT), will undergo a cycle of 10 LDL-apheresis session.

Apheretic treatment scheme: 10 apheretic session carried out as follow: first and second apheresis with a 3 days interval (i.e. 2 treatment in one week), then one session per week (every 7 days).

To perform the treatment, the forearm surface veins will be punctured by means of 17 Ga needles, as an alternative a two-ways CVC will be used.

Device: LDL-apheresis

The patient of the Arm "LDL-apheresis" in addition to standard therapy, will undergo a cycle of LDL-apheresis.

LDL-apheresis will be performed with B.Braun Avitum H.E.L.P. System. Apheretic treatment scheme: 10 apheretic sessions carried out as follows: the first 2 with a 3 day distance (i.e. 2 treatments in one week), successively 1 session per week (every 7 days).

To perform the treatment, the forearm surface veins will be punctured by means of 17 Ga needles, as an alternative a two-ways CVC will be used.

Other Names:
  • H.E.L.P. apheresis
  • TT: traditional therapy
No Intervention: Traditional Treatment

All patients will receive the traditional treatment for the ulcer healing Standardized medication.

All lesions taken into consideration will be treated in a standardized way, with a different approach according to the presence of a possible infection.

The evolution of lesions might be documented by means of mapping the same by drawing their profiles on an Opsite film.

antibiotics therapy (according to antibiogram). Anti-platelet therapy. Statin therapy.

  Show Detailed Description


Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diabetic patients
  • Ischemic diabetic ulcers (class I, II and III Texas Wound Classification System);
  • documented peripheral vasculopathy with at least a previous event of failed revascularization (no ulcer healing).

Exclusion Criteria:

  • Patient refusal to participate
  • BMI > 35 kg/m2
  • Ischemic diabetic ulcers class III Texas Wound Classification System
  • Patients presenting a bleeding diathesis, malignant tumor, heart failure not allowing extracorporeal technique.
  • Haemodialysis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01518205

Contact: Maria Grazia Zenti

universita Verona Recruiting
Verona, Italy, 37100
Contact: Maria Grazia Zenti, MD    +39 0458123745   
Sponsors and Collaborators
Universita di Verona
Principal Investigator: Maria Grazia Zenti, MD Division of Endocrinology and Metabolic Diseases, University Hospital of Verona
Study Director: Enzo Bonora, MD, PhD Division of Endocrinology and Metabolic Diseases, University Hospital of Verona
  More Information

No publications provided

Responsible Party: Maria Grazia Zenti, Maria Grazia Zenti,MD, Division of Endocrinology and Metabolic Diseases, University Hospital of Verona, Universita di Verona Identifier: NCT01518205     History of Changes
Other Study ID Numbers: MZenti HADIF
Study First Received: January 22, 2012
Last Updated: December 18, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by Universita di Verona:
diabetic foot ulcers,
peripheral arterial disease,
heparin-induced extracorporal lipid apheresis.
inflammatory markers
type 2 diabetes

Additional relevant MeSH terms:
Arteriosclerosis Obliterans
Diabetes Mellitus
Arterial Occlusive Diseases
Cardiovascular Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Vascular Diseases processed this record on February 27, 2015