To optimize glycemic control in acute ischemic stroke patients.
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Central nervous system vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The study has two primary endpoints
• 1) Glycemic control.
a) Mean glucose throughout protocol treatment
b) Percentage of time spent within target range.
• 2) Hypoglycemia
a) The total number of hypoglycemic events per group.
Hypoglycemia will be defined as any glucose value below 3.5 mmol/L.
b) Number of of serious hypoglycemic events (glucose value below 2.2
mmol/L)
c) Number of symptomatic confirmed events.
Secondary outcome
• Clinical outcome:
o Modified Rankin Score at three months follow-up (see appendix IV).
• Occurrence of pneumonia
• Treatment data:
o Total insulin dose U/dy en U/kg/dy
o Total amount of tube feeding administered
o Number of sensors inserted per patient
o Coefficient of Variation of CGMS derived glucose values
o Accuracy of FreeStyle Navigator, expressed as Mean Absolute Difference vs.
verification samples
Background summary
Post stroke hyperglycemia (HG) has been reported to negatively influence
cerebral infarction size, and clinical outcome in several series. In non-stroke
medical emergencies, prolonged treatment of HG with intensive insulin therapy
greatly reduces mortality in patients with acute myocardial infarction, in
intensive care patients and in patients undergoing coronary artery bypass
grafting. One randomized control trial has investigated the use of intensive
insulin therapy for HG in acute stroke, but no clinical effect was
demonstrated. Glycemic control in this trial, however, was poor and glycemic
control was continued for 24h only. We and others have reported previously that
effective glycemic control in stroke patients is not easy to accomplish.
Especially postprandial glucoses surges appeared difficult to control for. In a
subsequent study, we subjected ischemic stroke patients to tight glycemic
control (TGC) regime. This regime consisted in (i) continuous tube feeding;
(ii) a more stringent insulin treatment algorithm with an increased number of
glucose assessments, and (iii) a web-based program to assist nursing staff in
the execution of the algorithm. With this regime, including ten patients, we
were able to effectively maintain glucose values within a low physiological
range (below 6.1 mmol/L) for five consecutive days on a regular stroke unit.
This study had two drawbacks, however. First, TGC was accompanied by an
increased number of hypoglycemic episodes compared to normoglycemic or
hyperglycemic controls. Second, though inherent to the protocol design,
patients were subjected to continuous tube feeding (irrespective of the ability
to swallow) and to a high frequency of glucose assessments.
Continuous Glucose Monitoring Systems (CGM), which have recently become
available for clinical use, has the potential to improve glycemic control as
glucose levels out of target range (both high and low) can be anticipated much
faster.
Another interesting option is the addition of the selective inhibitor of
dipeptidyl peptidase-IV (DPP-4) vildagliptin (Galvus) to our treatment
protocol. It has been shown that addition of vildagliptin to insulin therapy is
associated with a reduction in HbA1c as well as a 30% reduction in
hypoglycemia.
Study objective
To optimize glycemic control in acute ischemic stroke patients.
Study design
This is a multi centre factorial randomised one arm open and one arm placebo
controlled trial.
Intervention
continuous tube feeding (vs. regular feeding)
Vildagliptin (vs. placebo)
IV insulin (all patients)
continuous glucose measurement (all patients)
Study burden and risks
Hypoglycemia
The main side effect of intensive insulin therapy is hypoglycemia. Mild
hypoglycemia for a short period
does not cause any damage in healthy individuals. Prolonged severe hypoglycemia
caused by excessive
insulin administration in normal individuals can cause neurological damage
leading to convulsions, coma
and death. Convulsions and coma can be seen in normal human subjects with
plasma glucose levels lower
than 1.5 mmol/l.
The first physiological response of the body during hypoglycemia is the
inhibition of insulin release
followed by an increase in glucagon release and other counterregulatory
hormones. Autonomic symptoms
such as anxiety, pallor, palpitations, restlessness, perspiration, tachycardia,
tremor and warmth, emerge
at plasma glucose levels below 3.2 mmol/l. Neuroglycopenic symptoms such as
confusion, drowsiness,
fatigue, inability to concentrate, irritability, lack of muscular coordination,
lightheadedness, paresthesia,
personality change, slurred speech and weakness follow if plasma glucose drops
below 2,8 mmol/l. These
symptoms and the autonomic symptoms are reversible.
Fingerprick:Periodic fingerpricks to control for glucsose values could be
inconvenient. During first 24 hrs
patients will be monitored for viatal signs each our as in standard care.
Fingerpricks will be intergrated in
these moments as much as possible.
Enteral tube feeding.
Patients can experience enteral tube feeding as incomfortable. Diarrhea and
local skin infections have
been reported.
AMC H2-222
1100 DE Amsterdam
Nederland
AMC H2-222
1100 DE Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
1) Supra-tentorial stroke with a time of onset within 24h before presentation.
2) An acute neurological deficit measurable with the National Institute of Health Stroke Score (NIHSS, see appendix I) >= 4 at presentation.
3) Venous plasma admission glucose > 7.0 mmol/l
4) Informed consent.
Exclusion criteria
1) Signs of cerebral hemorrhage on computed tomography scan
2) Previous history of diabetes mellitus treated with insulin
3) Patients in whom death appears imminent
4) Renal insufficiency defined as creatinine > 150 mmol/L
5) Patients under the age of 18
6) Pregnant patients
7) Expected transfer to a different hospital within 5 days.
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 | EUCTR2008-007020-25-NL |
| CCMO | NL26099.018.08 |