Effects of Insulin Treatment on Postprandial Platelet Activation in Patients With Non-insulin-dependent Diabetes Mellitus (NIDDM)

This study has been completed.
Sponsor:
Information provided by:
Karolinska Institutet
ClinicalTrials.gov Identifier:
NCT00771693
First received: October 10, 2008
Last updated: November 4, 2010
Last verified: November 2010
  Purpose

The postprandial phase in diabetic patients is characterized by a rapid increase in blood glucose levels, increase in platelet aggregation, LDL oxidation and over production of thrombin.

The aim of the study is to determine whether meal induced platelet activation is related to post-prandial hyperglycemia, and can be attenuated by good postprandial glucose control with rapidly acting insulin in patients with T2DM.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Postprandial Hyperglycemia
Drug: Insulin aspart (Novorapid®)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Effects of Insulin Treatment on Postprandial Platelet Activation in Patients With NIDDM: a Placebo-controlled Dose-response Study With Insulin Aspart (Novorapid®)

Resource links provided by NLM:


Further study details as provided by Karolinska Institutet:

Primary Outcome Measures:
  • To evaluate if platelet activation following a carbohydrate rich meal is related to the post-prandial hyperglycemia, and thus can be attenuated by premeal insulin treatment in patients with T2DM. [ Time Frame: 90 minutes after the meal ] [ Designated as safety issue: No ]
  • Co- primary platelet response variables: U46619 stimulated platelet P- selectin activation, platelet-leukocyte aggregation, platelet-platelet aggregates and platelet-monocyte aggregates. [ Time Frame: After completion of the study in 20 patients ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To elucidate if short-term lowering of blood glucose by insulin infusion (pretreatment standardization of blood glucose) reduces platelet activity in patients with T2DM. [ Time Frame: After completion of the glucose normalization (before the meal) ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: May 2007
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Insulin aspart (Novorapid®)
    a cross-over study with subcutaneous injection of insulin aspart 0.1U/kg, 0.2u/kg or placebo, before the meal, on 3 different occasions.
    Other Name: NovoRapid (Novo-Nordisk)
Detailed Description:

Each patient is admitted in the fasting state, on 3 different occasions . Blood glucose levels are normalized using intravenous infusion of insulin aspart , to a blood glucose level of 6-7 mmol/l. 15 minutes after normalization ,and right before a standardized meal, the patient is given a subcutaneous injection of insulin aspart 0.1 U/kg, 0.2 U/kg or placebo. The order of injections in the cross over study is randomized and blinded to the patient and to the investigators. The patient eats the meal and is followed up for 90 minutes after completion of the meal.

Blood tests for platelet function and other parameters are taken at 3 main points: 1. before glucose normalization.

2. 15 minutes after glucose normalization, and right before the meal. 3. 90 minutes after the meal.

Platelet function is evaluated by flow cytometry in whole blood (P- Selectin expression, Fibrinogen binding,aggregate formation: platelet- leukocyte, platelet-platelet, platelet-monocyte). Agonists that are used for platelet activation in flow cytometry are the thromboxane analogue U46619, ADP, and a collagen peptide that activates GPVI. Platelet adhesion is measured by the IMPACT cone and platelet analyser.

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type II Diabetes Mellitus.
  • Antecubital forearm veins allowing technically good sampling for platelet studies.
  • HbA1c 6-9 % (Mono-S method).
  • Below 70 years

Exclusion Criteria:

  • History of a cardiovascular disease; Ischemic heart disease, Stroke, Peripheral vascular disease.
  • Acute or chronic renal or liver disease
  • Contraindication to insulin treatment
  • Treatment with Glitazones, Sulphonylurea, antiplatelet drugs,
  • Thrombocytopenia <150 X109/l.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00771693

Locations
Sweden
Department of Medicine, Clinical pharmacology Unit, Karolinska University Hospital, Solna.
Stockholm, Sweden, SE 171 76
Sponsors and Collaborators
Karolinska Institutet
Investigators
Principal Investigator: Paul Hjemdahl, MD, PhD Department of Medicine, Clinical Pharmacology Unit, Karolinska institute, Stockhom, Sweden
  More Information

No publications provided by Karolinska Institutet

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof. Paul Hjemdahl, Dept Medicine Solna, Clinical Pharmacology Unit, Karolinska Institute, Stockholm, Sweden
ClinicalTrials.gov Identifier: NCT00771693     History of Changes
Other Study ID Numbers: EudraCT number 2006-007031-27
Study First Received: October 10, 2008
Last Updated: November 4, 2010
Health Authority: Sweden: Medical Products Agency

Keywords provided by Karolinska Institutet:
NIDDM
Platelet Activation
Postprandial hyperglycemia
insulin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin aspart
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014