Investigation Into Effects Upon Counterregulatory Responses to Hypoglycemia During Intensive Treatment of T1DM
Recruitment status was Recruiting
|First Received Date ICMJE||December 19, 2007|
|Last Updated Date||July 27, 2010|
|Start Date ICMJE||August 2001|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00580710 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Investigation Into Effects Upon Counterregulatory Responses to Hypoglycemia During Intensive Treatment of T1DM|
|Official Title ICMJE||Investigation Into Effects Upon Counterregulatory Responses to Hypoglycemia During Intensive Treatment of Insulin-dependent Diabetes Mellitus.|
This study is designed to investigate the effects of diabetes mellitus and its treatment upon the body's responses to low blood glucose (blood sugar) levels. Diabetes is a medical condition in which blood glucose can rise very high. Treatment of diabetes mellitus involves giving insulin (a hormone), which can occasionally cause blood glucose to fall too low. The body responds to low glucose levels by producing a number of hormones, which act against the insulin to help correct the low blood glucose. These hormones also provide symptoms which warn that the glucose is falling too far. These protective warnings by the body may be different in people with diabetes. We want to test whether this also means that diabetes changes the sensitivity of brain function to a lowering of blood glucose levels. In order to answer this question, we need to compare the response of people with diabetes with the response of people who do not have diabetes.
The plan of the study is to lower the subject's blood glucose using insulin, while measuring what changes occur in brain function using what is called functional magnetic resonance imaging (fMRI).
Previous studies have shown that a person with type 1 diabetes is less likely to suffer the long term microvascular complications of diabetes (eye, kidney and nerve damage) if they strive to achieve as near normal a blood glucose as possible. Unfortunately the tighter the blood glucose control is, the more likely the subject is to suffer episodes of hypoglycemia. Hypoglycemia is often the aspect of diabetes management most feared by people with diabetes and may cause more anxiety than the threat of advanced complications.
For many people with diabetes the problem of hypoglycemia is compounded by the development of the syndrome of hypoglycemia unawareness. One aspect of hypoglycemia unawareness is impairment of the hormones normally released as blood glucose falls. Hypoglycemia triggers a release of such insulin antagonists as epinephrine, norepinephrine, glucagon, growth hormone and cortisol. These hormones act synergistically with the autonomic nervous system to raise blood glucose, counteracting insulin and restoring normoglycemia. These homeostatic mechanisms are also responsible for some of the early symptoms of low blood glucose, providing a warning to insulin-treated diabetics as glucose falls. A number of studies including research from this unit have established that strict metabolic control is associated with impairment of the normal counterregulatory response to hypoglycemia and a loss of hypoglycemia awareness.
The brain is central to the recognition of hypoglycemia and the coordination of the counterregulatory response. Neural tissue depends mainly on glucose for its energy supply. As circulating glucose falls beneath the level needed to maintain glucose transport across the blood-brain barrier, a variety of defense mechanisms are activated, including symptoms of cognitive dysfunction. However, the precise nature and causes of the adverse CNS effects of hypoglycemia are not well understood.
Functional magnetic resonance imaging (fMRI) provides a tool to measure the effects of hypoglycemia on the patterns and magnitudes of neuronal activation in the human brain, in both normal and diabetic subjects.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Case Control
Time Perspective: Cross-Sectional
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Non-Probability Sample|
The recruited subjects will reflect the gender and ethnic distribution of the Yale and New Haven community. The recruited subjects with type 1 diabetes will reflect the demographics of the clinic population in New Haven. Subject selection is independent of race and sex.
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||75|
|Estimated Completion Date||August 2010|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 50 Years|
|Accepts Healthy Volunteers||Yes|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00580710|
|Other Study ID Numbers ICMJE||#0108012609, JDRF #4-2004-807|
|Has Data Monitoring Committee||Yes|
|Responsible Party||Robert Sherwin, M.D./Prinicipal Investigator, Yale University School of Medicine|
|Study Sponsor ICMJE||Yale University|
|Collaborators ICMJE||Juvenile Diabetes Research Foundation|
|Information Provided By||Yale University|
|Verification Date||July 2010|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP