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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
Sponsor:
Collaborators:
Dutch Diabetes Research Foundation
European Foundation for the Study of Diabetes
Information provided by (Responsible Party):
Radboud University

Tracking Information
First Submitted Date  ICMJE May 21, 2014
First Posted Date  ICMJE May 23, 2014
Last Update Posted Date November 10, 2015
Study Start Date  ICMJE August 2014
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 9, 2015)
Brain lactate concentration [ Time Frame: during stable euglycemia and hypoglyemia ]
Concentration brain lactate measured with 1H-MRS
Original Primary Outcome Measures  ICMJE
 (submitted: May 22, 2014)
  • Brain lactate concentration [ Time Frame: during 30 minutes of hypoglycemia or euglycemia ]
    Concentration brain lactate measured with 1H-MRS
  • Brain lactate concentration [ Time Frame: during 30 minutes of hypoglycemia or euglycemia ]
    Concentration brain lactate measured with 1H magnetic resonance spectroscopy (MRS)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 9, 2015)
  • Plasma lactate levels [ Time Frame: during stable euglycemia and hypoglyemia ]
    Concentration arterial plasma lactate
  • Hormone response [ Time Frame: during stable euglycemia and hypoglyemia ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Hypoglycaemia on Brain Lactate Accumulation and Cerebral Blood Flow
Official Title  ICMJE 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
Brief Summary

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).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Type 1 Diabetes Mellitus
  • Hypoglycemia Unawareness
Intervention  ICMJE
  • Other: hypoglycemia
    Blood glucose levels will be kept at ~3.0 mmol/l
    Other Name: Low blood glucose levels
  • Other: euglycemia
    Blood glucose levels will be kept at ~5.0 mmol/l
    Other Name: Normal blood glucose levels
Study Arms  ICMJE
  • Active Comparator: Euglycemia
    Plasma glucose levels will be clamped at a constant value of ~5.0 mmol/l
    Intervention: Other: euglycemia
  • Experimental: Hypoglycemia
    Plasma glucose levels will be clamped at a stable value of ~3.0 mmol/l
    Intervention: Other: hypoglycemia
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 22, 2014)
21
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 2015
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria for healthy subjects

  • Age: 18-50 years
  • Body-Mass Index: 18-30 kg/m2
  • Blood pressure: <160/90 mmHg

Inclusion criteria T1DM patients with normal hypoglycemic awareness

  • Diabetes duration ≥ 1 year
  • Age: 18-50 years
  • Body-Mass Index: 18-30 kg/m2
  • HbA1c: 42-75 mmol/mol (6-9%)
  • Outcome Clarke questionnaire: 0-1
  • Blood pressure: <160/90 mmHg

Inclusion criteria T1DM patients with hypoglycemia unawareness

  • Diabetes duration ≥ 1 year
  • Age: 18-50 years
  • Body-Mass Index: 18-30 kg/m2
  • HbA1c: 42-75 mmol/mol (6-9%)
  • Outcome Clarke questionnaire: >3
  • Blood pressure: <160/90 mmHg

Exclusion criteria for healthy subjects

  • Inability to provide informed consent
  • Presence of any medical condition that might interfere with the study protocol, such as brain injuries, epilepsy, a major cardiovascular disease event or anxiety disorders
  • Use of any medication, except for oral contraceptives
  • MR(I) contraindications (pregnancy, severe claustrophobia, metal parts in body)

Exclusion criteria for all T1DM patients

  • Inability to provide informed consent
  • Presence of any other medical condition that might interfere with the study protocol, such as brain injuries, epilepsy, a major cardiovascular disease event, anxiety disorders, or complications of T1DM (including neuropathy and retinopathy)
  • Use of any other medication than insulin, except for oral contraceptives or stable thyroxine supplementation therapy
  • MR(I) contraindications (pregnancy, severe claustrophobia, metal parts in body)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02146404
Other Study ID Numbers  ICMJE 1H_lac_acc
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Radboud University
Study Sponsor  ICMJE Radboud University
Collaborators  ICMJE
  • Dutch Diabetes Research Foundation
  • European Foundation for the Study of Diabetes
Investigators  ICMJE
Principal Investigator: Bastiaan de Galan, Dr. Radboud UMC
PRS Account Radboud University
Verification Date November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP