We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effects of Hypoglycaemia in People With Type 2 Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02205996
Recruitment Status : Completed
First Posted : August 1, 2014
Last Update Posted : August 1, 2014
Sponsor:
Collaborator:
Hull University Teaching Hospitals NHS Trust
Information provided by (Responsible Party):
Thozhukat Sathyapalan, University of Hull

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
Strict glycaemic control has been associated with increased hypoglycaemia and mortality rate, the cause of which was unclear, in subjects with type 2 diabetes. In this study, we hypothesised that acute hypoglycaemia will result in platelet activation in people with type 2 diabetes to a higher degree than controls.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Insulin (Humulin S) Device: Euglycaemic Hypoglycaemic Insulin clamp Not Applicable

Detailed Description:

Type 2 diabetes is associated with increased risk of cardiovascular disease. Although the United Kingdom Prospective Diabetes Study (UKPDS) follow-up data suggested reduced macrovascular complications with tight glycaemic control, recent studies in people with type 2 diabetes failed to replicate these findings. Furthermore, all-cause mortality was found to be increased with strict glycaemic control in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. The cause of the increased deaths remains unclear.

Strict glycaemic control is associated with increased risk of hypoglycaemia. Although, hypoglycaemia has traditionally been considered a complication of the treatment for type 1 diabetes, it has recently been recognised as a problem in people with type 2 diabetes particularly those on insulin therapy. In the ACCORD study, the risk of death was significantly increased in those with one or more episode of severe hypoglycaemia in both the strict and standard study treatment arms. As plasma glucose falls to below 4.0 mmol/L, a series of defence mechanisms occur, at an individualised glycaemic thresholds, to reverse hypoglycaemia including a rise in catecholamine levels. This may lead to hypokalaemia, prolonged QT interval, and cardiac arrhythmias. It may also lead to impaired cardiovascular autonomic function for up to 16 hours afterwards; increased inflammatory markers; platelet activation and promote vascular damage. As the majority of studies assessing the effects of hypoglycaemia on cardiovascular risk markers are conducted in people with type 1 diabetes and healthy controls, their findings may not necessarily be applicable to people with type 2 diabetes. In particular, the effects of hypoglycaemia on platelet function and thrombotic risk in people with type 2 diabetes require further clarification. In this study, we hypothesised that acute hypoglycaemia will result in platelet activation in people with type 2 diabetes to a higher degree than controls.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: The Effects of Hypoglycaemia on Platelets Function and Inflammatory Markers in People With Type 2 Diabetes and Normal Controls.
Study Start Date : November 2011
Actual Primary Completion Date : May 2013
Actual Study Completion Date : May 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypoglycemia

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Active Comparator: Controls
Weight-matched healthy controls. Euglycaemic Hypoglycaemic insulin clamp. Using hyperinsulinaemic clamps, blood glucose levels were stabilised over 1 hour to reach 5 mmol/L and maintained at that level for 1 hour, then gradually reduced over 1 hour to 2.8 mmol/L and maintained at that level for 1 hour. Blood samples were collected at times 0 (baseline), 2 hours (euglycaemia), 4 hours (hypoglycaemia) and at 24 hours after the clamp studies.
 Drug: Insulin (Humulin S)
Using insulin and glucose infusions (hyperinsulinaemic clamps), blood glucose levels were stabilised over 1 hour to reach 5 mmol/L and maintained at that level for 1 hour, then gradually reduced over 1 hour to 2.8 mmol/L and maintained at that level for 1 hour. Blood samples were collected at times 0 (baseline), 2 hours (euglycaemia), 4 hours (hypoglycaemia) and at 24 hours after the clamp studies.
Other Name: Glucose (20% Dextrose).

Device: Euglycaemic Hypoglycaemic Insulin clamp
Active Comparator: Type 2 diabetes
People with a known diagnosis of type 2 diabetes. Euglycaemic Hypoglycaemic Insulin clamp. Using hyperinsulinaemic clamps, blood glucose levels were stabilised over 1 hour to reach 5 mmol/L and maintained at that level for 1 hour, then gradually reduced over 1 hour to 2.8 mmol/L and maintained at that level for 1 hour. Blood samples were collected at times 0 (baseline), 2 hours (euglycaemia), 4 hours (hypoglycaemia) and at 24 hours after the clamp studies.
 Drug: Insulin (Humulin S)
Using insulin and glucose infusions (hyperinsulinaemic clamps), blood glucose levels were stabilised over 1 hour to reach 5 mmol/L and maintained at that level for 1 hour, then gradually reduced over 1 hour to 2.8 mmol/L and maintained at that level for 1 hour. Blood samples were collected at times 0 (baseline), 2 hours (euglycaemia), 4 hours (hypoglycaemia) and at 24 hours after the clamp studies.
Other Name: Glucose (20% Dextrose).

Device: Euglycaemic Hypoglycaemic Insulin clamp


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. To examine the effect of hypoglycaemia on platelet surface expression of platelet activation markers P-selectin and fibrinogen binding. [ Time Frame: Up to 24 hours after euglycaemic hypoglycaemic clamp ]

    Platelet surface expression of activation markers, P-selectin and fibrinogen binding, were measured in the resting state (unstimulated samples) and in response to stimulation with platelet agonist adenosine diphosphate, and platelet inhibitor prostacyclin.

    A change in platelet function from times 0 (baseline), to 2 hours (euglycaemia), 4 hours (hypoglycaemia) and 24 hours after the clamp studies was measured and compared between the two groups.



Secondary Outcome Measures :
  1. To measure changes in markers of inflammation (high sensitivity C-reactive protein) and endothelial function using EndoPat 2000 [ Time Frame: Up to 24h after euglycaemic hypoglycaemic clamp ]

    High sensitivity C-reactive protein was measured at baseline (time 0), 2 hours (euglycaemia), 4 hours (hypoglycaemia) and 24 hours after clamp studies. Changes from baseline were compared between the groups.

    EndoPat was measured before the insulin clamp and 24 hours afterwards and changes were compared between the two groups.



Other Outcome Measures:
  1. To assess the effects of hypoglycaemia on participants scores on cognitive function tests [ Time Frame: Up to 24h after euglycaemic hypoglycaemic clamp ]
    Three cognitive function tests (Tower of Hanoi; Dual Task test and The Digit symbol-coding) were measured at baseline (time 0), 2 hours (euglycaemia), 4 hours (hypoglycaemia) and 24 hours after insulin clamp studies. Changes from baseline in each of these tests in response to the insulin clamp were compared between the two groups.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy volunteers:

    • Males or females
    • On no medications except for the contraceptive pill and without medical illnesses in the last three months.
    • Non-smokers
    • 40 - 60 years of age.

  2. T2DM subjects:

    • Males or females
    • Diagnosis of T2DM
    • 40 - 60 years of age
    • HbA1C: 6.5 - 9.5%
    • Duration of diabetes 1 - 10 years
    • Diabetes treated with diet, or tablets only.

Exclusion Criteria:

  1. Healthy volunteers:

    • Pregnancy
    • Lack of contraception in women of child bearing age
    • Chronic medical conditions
    • Current smokers
    • Evidence of ischaemia on ECG
    • Drop attacks
    • Alcohol or drug abuse
    • Psychiatric illness
    • Previous history of seizure
    • Alcohol or drug abuse

  2. Type 2 diabetes subjects:

    • Pregnancy
    • Current smokers
    • Recurrent episodes of hypoglycaemia
    • Treatment with anti-platelet or anti-coagulation therapy
    • History of ischaemic heart disease, stroke or peripheral vascular disease
    • Epilepsy
    • Drop attacks
    • Evidence of ischaemia on ECG
    • Insulin treated T2DM
    • History of microvascular disease (retinopathy, nephropathy or neuropathy).
    • Alcohol or drug abuse
    • Psychiatric illness
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02205996


Locations
Layout table for location information
United Kingdom
Hull Royal Infirmary
Hull, United Kingdom, HU3 2RW
Sponsors and Collaborators
University of Hull
Hull University Teaching Hospitals NHS Trust
Investigators
Layout table for investigator information
Principal Investigator: Stephen L Atkin, PhD Hull York Medical School
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Thozhukat Sathyapalan, Dr, University of Hull
ClinicalTrials.gov Identifier: NCT02205996    
Other Study ID Numbers: 11/YH/0161
First Posted: August 1, 2014    Key Record Dates
Last Update Posted: August 1, 2014
Last Verified: July 2014
Keywords provided by Thozhukat Sathyapalan, University of Hull:
Type 2 diabetes
Hypoglycaemia
Platelets
Inflammation
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
 Endocrine System Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs