To investigate the effect of intravenous lactate administration, compared to placebo, on thalamic (regional) and global CBF during euglycemia and hypoglycemia in patients with T1DM and NAH.
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The change in regional thalamic CBF in response to intravenous lactate infusion
compared to placebo, during hypoglycemia
Secondary outcome
- Change in global CBF in response to intravenous lactate infusion compared to
placebo, during hypoglycemia
- Change in plasma levels of counterregulatory hormones in response to
hypoglycemia and euglycemia with and without lactate infusion (adrenaline,
noradrenaline, growth hormone and cortisol)
- Change in hypoglycemic symptoms scores in response to hypoglycemia with and
without lactate infusion
Background summary
It is thought that altered brain lactate handling is involved in the
development of impaired awareness of hypoglycemia (IAH), i.e. the inability to
timely detect hypoglycemia in people with type 1 diabetes (T1DM). Infusion of
lactate diminishes symptomatic and hormonal responses to hypoglycemia in
patients with normal awareness of hypolgycemia (NAH), resembling the situation
of patients with IAH. It is unknown whether this attenuating effect is due to
brain lactate oxidation or the result of lactate-induced alterations of global
and regional cerebral blood flow (CBF).
Normally, hypoglycemia causes a redistribution of CBF towards the thalamus,
from where the sympathetic response to hypoglycemia is coordinated, but in IAH
this effect is absent and global CBF is increased. We hypothesize that lactate
infusion in patients with NAH will result in blunting of thalamic activation
and/or enhanced global CBF. If so, these results may help delineating the
pathogenesis of IAH which eventually creates new avenues to protect against the
morbidity associated with hypoglycemia and IAH.
Study objective
To investigate the effect of intravenous lactate administration, compared to
placebo, on thalamic (regional) and global CBF during euglycemia and
hypoglycemia in patients with T1DM and NAH.
Study design
Single-blind placebo controlled, randomized cross-over intervention study
Intervention
On two separate occasions, patients with T1DM and NAH will undergo a
hyperinsulinemic euglycemic-hypoglycemic glucose clamp with or without the
infusion of exogenous lactate. ASL-MRI will be applied to measure global and
regional changes in CBF.
Study burden and risks
The hypoglycemic condition is likely to induce typical symptoms (e.g. sweating,
feeling hungry, palpitations) in T1DM patients with NAH, but is usually
well-tolerated and less pronounced when lactate is infused. The risk for more
severe hypoglycemia is negligible. The use of venous and arterial catheters may
lead to hematomas and/or phlebitis, yet this is self-limiting and has in our
hands never led to permanent damage. ASL-MRI is a non-invasive method to
determine CBF, involving high magnetic fields, which are not associated with
adverse events other than possible claustrophobia due to lying in the small
MR-bore.
Geert Grooteplein 10
Nijmegen 6500 HB
NL
Geert Grooteplein 10
Nijmegen 6500 HB
NL
Listed location countries
Age
Inclusion criteria
- Diabetes duration * 1 year
- Age: 18-50 years
- Body-Mass Index: 18-30 kg/m2
- HbA1c: <75 mmol/mol (<9%)
- Outcome Clarke questionnaire: 0-1
- Blood pressure: <160/90 mmHg
Exclusion criteria
- Inability to provide informed consent
- Use medication other than insulin, except for oral contraceptives or stable thyroxin supplementation therapy
- Presence of any other medical condition that might interfere with the study protocol, such as brain injuries, epilepsy, a major cardiovascular disease event or cardiac failure, known liver disease, anxiety disorders or a history of panic attacks.
- Microvascular complications of T1DM
- MRI contraindications (pregnancy, severe claustrophobia, metal parts in body)
Design
Recruitment
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 | EUCTR2018-000684-82-NL |
| CCMO | NL64421.091.18 |
| Other | nog niet bekend |