Normalization of Fasting Glucose and the Incidence of Restenosis After Peripheral Angioplasty (LIMBISCH)
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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. |
- 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.
- 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
Other Names:
|
|
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
Other Names:
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 30 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Both genders
- Age between 30 and 75 years
- 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
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
- Angiographic documentation of infrapopliteal arterial disease (stenosis >70% or occlusion)
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.
- Subject able to provide a signed and dated written informed consent
Exclusion Criteria:
- Type 1 diabetes, defined as positivity for GAD antibodies measured by radiobinding assay
- Unwilling to inject insulin or to perform a correct self monitoring of blood glucose
- Acute limb ischemia
- Buerger disease
- Severe contrast allergy
- Hypersensitivity to aspirin and/or clopidogrel
- Systemic coagulopathy contraindicating antiaggregation therapy
- Hypercoagulation disorder
- Serum creatinine>2.0 mg/dl at screening
- Active liver disease, or ALT or AST >2.5 times upper limit of normal at screening
- Chronic or recurrent treatment with systemic corticosteroids
- Malignant diseases
- Psychiatric diseases which make participation impossible
- Alcohol abuse
Contacts and Locations| Italy | |
| Cardio-Metabolic and Clinical Trials Unit, San Raffaele Scientific Institute | |
| Milan, Italy, 20132 | |
| 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 May 19, 2013