The effect of hypoglycaemia on brain lactate accumulation and cerebral blood flow

• Conditions: Type 1 Diabetes Mellitus and Hypoglycemia Unawareness; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2014-001777-13-NL
• Lead Sponsor: Radboud umc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-06-03
• Last Update Posted: 27 October 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 21
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main 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. ;Secondary Objective: The secondary objective is to assess whether this effect is a related to hypoglycemia unawareness or a consequence of T1DM per se.;Primary end point(s): The main study parameter is the concentration of lactate expressed both relative to the creatine concentration in the brain and quantitatively (mmol/L).;Timepoint(s) of evaluation of this end point: Brain lactate concentration will be measured at ~5 minutes interval

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -Level of plasma counterregulatory hormones (glucagon, adrenaline, noradrenaline, growth hormone and cortisol) (pmol/L)<br>-Glucose infusion rate (GIR): the amount of glucose 20% necessary to maintain plasma glucose at steady state euglycemic or hypoglycemic values (mg·kg-1·min-1)<br>-Brain perfusion, determined by arterial spin labelling (ASL) MRI, measured twice (at stable euglycemic and hypoglycemic levels) (ml/min)<br>-Hypoglycemic symptoms scores<br>-Plasma lactate concentration (mmol/L)<br>;Timepoint(s) of evaluation of this end point: - GIR: 5 minutes interval<br>-CBF: 1 time per glycemic phase<br>- Hypoglycemic symptom score: every 30 minutes<br>- Plasma lactate concentration: 5 minute interval