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NCT Number: NCT02146404

The Effect of Hypoglycaemia on Brain Lactate Accumulation and Cerebral Blood Flow

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).

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Key information

Conditions

Type 1 Diabetes Mellitus Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus, Type 1 Endocrine System Diseases Glucose Metabolism Disorders Hypoglycemia Unawareness Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Radboud umc

Nijmegen, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

hypoglycemia

Other

Blood glucose levels will be kept at ~3.0 mmol/l

Other names: Low blood glucose levels

euglycemia

Other

Blood glucose levels will be kept at ~5.0 mmol/l

Other names: Normal blood glucose levels

Primary outcomes

  1. Brain lactate concentration

    Time frame: during stable euglycemia and hypoglyemia

    Concentration brain lactate measured with 1H-MRS

Secondary outcomes

  1. Plasma lactate levels

    Time frame: during stable euglycemia and hypoglyemia

    Concentration arterial plasma lactate

  2. Hormone response

    Time frame: during stable euglycemia and hypoglyemia

Sponsors and collaborators

Lead sponsor

Radboud University Medical Center

Other

Collaborators

  • Dutch Diabetes Research Foundation
  • European Foundation for the Study of Diabetes

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
May 23, 2014
Registry last updated
Nov 10, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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