The Effect of Hypoglycaemia on Brain Lactate Accumulation and Cerebral Blood Flow
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|ClinicalTrials.gov Identifier: NCT02146404|
Recruitment Status : Completed
First Posted : May 23, 2014
Last Update Posted : November 10, 2015
Iatrogenic hypoglycemia is the most frequent acute complication of insulin therapy in people with type 1 diabetes (T1DM). Recurrent hypoglycemic events initiate a process of habituation, characterized by suppression of hypoglycemic symptoms and lead to hypoglycemia unawareness, which in itself defines a particularly high risk of severe hypoglycemia. Recent evidence suggest a pivotal role for increased brain lactate transport capacity in the pathogenesis of hypoglycemia unawareness. However, there is uncertainty about the magnitude of this effect and whether such excess brain lactate is oxidizes as a glucose-sparing alternative energy source or acts as a metabolic regulator controlling brain glucose metabolism, oxygen consumption and cerebral blood flow.
Objective: The primary objective of this study is to investigate the effect of hypoglycemia on brain lactate accumulation and regional cerebral blood perfusion in humans. The secondary objective is to assess whether this effect is a related to hypoglycemia unawareness or a consequence of T1DM per se.
Hypothesis: The investigators hypothesize that hypoglycemia stimulates lactate transport over the blood-brain barrier leading to cerebral lactate accumulation and that this lactate accumulation is a function of prior hypoglycemic exposure frequency contributing to clinical hypoglycemia unawareness. Furthermore, the investigators expect that this effect of hypoglycemia on brain lactate accumulation is related to changes in cerebral blood flow (CBF).
|Condition or disease||Intervention/treatment||Phase|
|Type 1 Diabetes Mellitus Hypoglycemia Unawareness||Other: hypoglycemia Other: euglycemia||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||The Effect of Insulin-induced Hypoglycemia on Brain Lactate Accumulation and Regional Cerebral Blood Flow in Patients With Type 1 Diabetes Mellitus With and Without Hypoglycemia Unawareness and Non-diabetic Controls|
|Study Start Date :||August 2014|
|Actual Primary Completion Date :||October 2015|
|Actual Study Completion Date :||October 2015|
Active Comparator: Euglycemia
Plasma glucose levels will be clamped at a constant value of ~5.0 mmol/l
Blood glucose levels will be kept at ~5.0 mmol/l
Other Name: Normal blood glucose levels
Plasma glucose levels will be clamped at a stable value of ~3.0 mmol/l
Blood glucose levels will be kept at ~3.0 mmol/l
Other Name: Low blood glucose levels
- Brain lactate concentration [ Time Frame: during stable euglycemia and hypoglyemia ]Concentration brain lactate measured with 1H-MRS
- Plasma lactate levels [ Time Frame: during stable euglycemia and hypoglyemia ]Concentration arterial plasma lactate
- Hormone response [ Time Frame: during stable euglycemia and hypoglyemia ]
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): NCT02146404
|Principal Investigator:||Bastiaan de Galan, Dr.||Radboud UMC|