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…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the concentration of lactate in the brain.
Secondary outcome
Secondary endpoints will be:
- Level of plasma counterregulatory hormones (glucagon, adrenaline,
noradrenaline, growth hormone and cortisol) (pmol/L)
- 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)
- Brain perfusion, determined by arterial spin labelling (ASL) MRI, measured
twice (at stable euglycemic and hypoglycemic levels) (ml/min)
- Hypoglycemic symptoms scores
- Plasma lactate concentration (mmol/L)
Other study parameters
- Plasma glucose concentration (mmol/L)
- Plasma insulin concentration (pmol/L)
Background summary
Iatrogenic hypoglycemia is the most frequent acute complication of insulin
therapy in people with type 1 diabetes. 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.
Study 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.
Study design
Cross-over intervention study
Intervention
Hyperinsulinemic stepped euglycemic-hypoglycemic glucose clamps, where plasma
glucose levels will be clamped at ~5.0 mmol/l for 30 minutes and subsequently
at ~3.0 mmol/l for another 30 minutes, will be performed. 1H magnetic resonance
spectroscopy (MRS) will be applied during the whole test to measure brain
lactate levels, and arterial spin labeling (ASL) will be used to measure brain
perfusion.
Study burden and risks
The hypoglycemic condition is likely to produce typical symptoms (e.g.
sweating, feeling hungry, palpitations) in healthy volunteers and T1DM patients
with intact hpoglycemic awareness, but is usually well-tolerated and the risk
for more severe hypoglycemia is negligible. The use of venous and arterial
catheters may lead to hematomas, yet this is self-limiting and has in our hands
never lead to permanent damage. 1H-MRS is a non-invasive method involving high
magnetic fields, which is not associated with adverse events other than
possible claustrophobia due to lying in the small MR-bore.
Geert Grooteplein 10
Nijmegen 6525 GA
NL
Geert Grooteplein 10
Nijmegen 6525 GA
NL
Listed location countries
Age
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
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)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-001777-13-NL |
| CCMO | NL49093.091.14 |
| Other | nog niet bekend |