Normalization of Fasting Glucose and the Incidence of Restenosis After Peripheral Angioplasty (LIMBISCH)

This study has been terminated.
(end-point reached)
Sponsor:
Information provided by (Responsible Party):
PierMarco Piatti, IRCCS San Raffaele
ClinicalTrials.gov Identifier:
NCT01150617
First received: June 23, 2010
Last updated: September 12, 2012
Last verified: September 2012
  Purpose

Primary objective of the study is to test whether an intensified insulin therapy incorporating the target of normal fasting glucose (<5.5 mmol/L) and glycated hemoglobin <6.5% is able to halve the incidence of angiographic restenosis at 6 months (expected rate 45%, to be reduced at 15%) after peripheral angioplasty compared with standard care to achieve a glycated hemoglobin <7.0% in patients with type 2 diabetes and limb ischemia.

Secondary objectives include the identification of markers associated with, and predictive of, restenosis and the investigation of the underlying pathophysiological background, with specific focus on the role of nitric oxide (NO), mechanisms of endothelial activation/apoptosis, inflammation and matrix remodeling risk profiles, candidate gene polymorphisms and endothelial progenitor cells evaluation.

Methodology: This is a randomized, open-label, clinical trial comparing two regimens of insulin therapy having as an outcome measure the incidence of angiographic restenosis at 6 months after peripheral angioplasty. Seventy consecutive patients with type 2 diabetes and peripheral arterial disease undergoing peripheral angiography and subsequent angioplastic procedure will be studied. Patients will be treated by intensive insulin therapy, based on three pre-prandial administrations of regular insulin or short acting insulin analogues combined with the long-acting insulin analogue glargine or standard care based on once-daily insulin and oral antidiabetics agents. Patients randomized to the intensive insulin therapy arm will be educated and followed up with daily measurements of fasting glucose and weekly phone contacts with the target of fasting glucose <5.5 mmol/L (99 mg/dl) to obtain glycated hemoglobin <6.5%. The control arm will be followed to achieve a target of glycated hemoglobin <7.0%. Life style recommendations, including diet and physical activity program, will be the same for the two arms. All patients will undergo three visits with physical examination and blood sampling, at baseline and at 2, 4 and 6 months after angioplasty. Moreover, patients on normal fasting glucose arm will be monitored by phone on weekly basis in order to test their adherence to therapeutic target.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Peripheral Vascular Disease
Drug: Insulin glargine plus insulin analogues
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Normalization of Fasting Glucose by Intensified Insulin Therapy on the Incidence of Restenosis After Peripheral Angioplasty in Patients With Type 2 Diabetes.

Resource links provided by NLM:


Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:
  • Reduction of restenosis after peripheral angioplasty [ Time Frame: 6 months, average up to 30 weeks ] [ Designated as safety issue: Yes ]
    Primary objective of the study is to test whether an intensified insulin therapy incorporating the target of normal fasting glucose (<5.5 mmol/L) and glycated hemoglobin <6.5% is able to halve the incidence of angiographic restenosis at 6 months (expected rate 45%, to be reduced at 15%) after peripheral angioplasty compared with standard care to achieve a glycated hemoglobin <7.0% in patients with type 2 diabetes and limb ischemia.


Secondary Outcome Measures:
  • Identification of new peripheral markers predictive of restenosis [ Time Frame: 6 months, average up to 30 weeks ] [ Designated as safety issue: No ]
    Secondary objectives include the identification of markers associated with, and predictive of, restenosis and the investigation of the underlying pathophysiological background, with specific focus on the role of nitric oxide (NO), mechanisms of endothelial activation/apoptosis, inflammation and matrix remodeling risk profiles, candidate gene polymorphisms and endothelial progenitor cells evaluation.


Enrollment: 46
Study Start Date: December 2008
Study Completion Date: May 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: long-acting insulin plus analogues
three administrations of regular insulin or short acting insulin analogues before meals combined with long-acting insulin analogue glargine in the evening.
Drug: Insulin glargine plus insulin analogues
  • Intensified insulin therapy: three administrations of regular insulin or short acting insulin analogues before meals combined with long-acting insulin analogue glargine in the evening. The treatment goal will be a fasting blood glucose level of 5.5 mmol/L (99 mg/dl) and a HbA1c<6.5% at the end of the follow-up.
  • Standard care: treatment will be once-daily long-acting insulin and oral antidiabetic agents to achieve HbA1c levels of < 7.0% at the end of the follow-up.
Other Names:
  • Insulin glargine plus short acting insulin analogues
  • Insulin glargine plus hypoglycemic agents
Active Comparator: long-acting insulin and oral agents
treatment will be once-daily long-acting insulin and oral antidiabetic agents
Drug: Insulin glargine plus insulin analogues
  • Intensified insulin therapy: three administrations of regular insulin or short acting insulin analogues before meals combined with long-acting insulin analogue glargine in the evening. The treatment goal will be a fasting blood glucose level of 5.5 mmol/L (99 mg/dl) and a HbA1c<6.5% at the end of the follow-up.
  • Standard care: treatment will be once-daily long-acting insulin and oral antidiabetic agents to achieve HbA1c levels of < 7.0% at the end of the follow-up.
Other Names:
  • Insulin glargine plus short acting insulin analogues
  • Insulin glargine plus hypoglycemic agents

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Both genders
  2. Age between 30 and 75 years
  3. Early type 2 diabetes, defined as FPG >7.0 mmol/l or a PPG of 11.1 mmol/l or greater or a previous diagnosis of diabetes
  4. Treatments accepted

    • Diet without pharmacological treatment
    • One or more oral antidiabetic drug (OAD: sulfonylureas, biguanides, meglitinides) at half-maximum dose or greater
    • Once daily insulin and OAD
  5. Angiographic documentation of infrapopliteal arterial disease (stenosis >70% or occlusion)
  6. Critical limb ischemia (CLI) defined as

    • Persistent, recurring rest pain requiring analgesia and an ankle systolic pressure <50 mm Hg and/or toe systolic pressure <30 mm Hg or TcPO2 <30 mm Hg
    • Ulceration, gangrene, or nonhealing wounds of the foot with ankle systolic pressure <50 mm Hg or toe systolic pressure <30 mm Hg or TcPO2 <30 mm Hg
    • Fontaine stages III-IV and rutherford categories IV-VI
    • Lifestyle-limiting claudication defined as Rutherford category II to III associated with jeopardized single vessel runoff or complete trifurcation vessel occlusion.
  7. Subject able to provide a signed and dated written informed consent

Exclusion Criteria:

  1. Type 1 diabetes, defined as positivity for GAD antibodies measured by radiobinding assay
  2. Unwilling to inject insulin or to perform a correct self monitoring of blood glucose
  3. Acute limb ischemia
  4. Buerger disease
  5. Severe contrast allergy
  6. Hypersensitivity to aspirin and/or clopidogrel
  7. Systemic coagulopathy contraindicating antiaggregation therapy
  8. Hypercoagulation disorder
  9. Serum creatinine>2.0 mg/dl at screening
  10. Active liver disease, or ALT or AST >2.5 times upper limit of normal at screening
  11. Chronic or recurrent treatment with systemic corticosteroids
  12. Malignant diseases
  13. Psychiatric diseases which make participation impossible
  14. Alcohol abuse
  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 ClinicalTrials.gov identifier: NCT01150617

Locations
Italy
Cardio-Metabolic and Clinical Trials Unit, San Raffaele Scientific Institute
Milan, Italy, 20132
Sponsors and Collaborators
IRCCS San Raffaele
Investigators
Principal Investigator: PierMarco Piatti, MD San Raffaele Scientific Institute, Milan
  More Information

No publications provided

Responsible Party: PierMarco Piatti, PI, IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT01150617     History of Changes
Other Study ID Numbers: Limb ischemia
Study First Received: June 23, 2010
Last Updated: September 12, 2012
Health Authority: Italy: Ministry of Health

Keywords provided by IRCCS San Raffaele:
Type 2 diabetes mellitus
Normoglycemia
Peripheral angioplasty

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Vascular Diseases
Peripheral Vascular Diseases
Peripheral Arterial Disease
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Cardiovascular Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Glargine
Insulin
Hypoglycemic Agents
Insulin, Long-Acting
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014