Normoglycemia and Neurological Outcome

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
University of Louisville
ClinicalTrials.gov Identifier:
NCT01137773
First received: June 3, 2010
Last updated: November 12, 2012
Last verified: November 2012
  Purpose

Brain injury patients who meet defined criteria will be assigned to intensive insulin treatment (target blood glucose levels of 10-110 mg/dl) or conventional IV insulin treatment (target glucose of 150-170 mg/dl). Follow up will occur at 3, 6 and 12 months. The primary outcome measure will be neurological outcome at 12 months according to Glasgow Outcome Scale Expanded (GOSE) and Karnofsky Performance Scale (KPS). A general view of outcome will also be presented as favorable (good recovery+ moderate disability), unfavorable (severely disabled+ vegetative state), and dead.

Secondary outcome measures will be length of stay in the intensive care unit and the hospital, the need for ventilatory support or renal replacement therapy, inotropic and vasopressor support, transfusion requirements, and death. Likewise, incidence of seizures and diabetes insipidus will be measured. The investigators will also record systemic complications like pulmonary emboli, pulmonary edema, myocardial infarction, ventricular arrhythmias, and pneumonia.


Condition Intervention Phase
Acute, Non-traumatic Subarachnoid Hemorrhage
Intraparenchymal Hemorrhage
Brain Injuries
Drug: Insulin
Drug: Conventional insulin treatment
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Does Maintenance of Normoglycemia Change Neurological Outcome in Patients Recovering From Traumatic Brain Injury and Subarachnoid or Intraparenchymal Hemorrhage?

Resource links provided by NLM:


Further study details as provided by University of Louisville:

Primary Outcome Measures:
  • Glasgow Outcomes Scale Extended score [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The Glasgow Outcome Scale (GOS) is the most widely used measure for traumatic brain injury and other non-traumatic brain injuries and is favored over other measures such as disability rating scale.


Secondary Outcome Measures:
  • Karnofsky Performance Scale (KPS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The Karnofsky Performance Scale (KPS) was originally intended for debilitating diseases such as terminal cancer, but it is currently also used for evaluation of quality of life and long term rehabilitation.


Estimated Enrollment: 360
Study Start Date: January 2007
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intensive IV Insulin
Patients will receive IV insulin to maintain target glucose levels of 80-110 mg/dl
Drug: Insulin
All patients in the trial will have blood taken hourly for glucose analysis, regardless of their designated group. Adjustments of the insulin dose will be based on measurements of capillary blood glucose level.
Active Comparator: Conventional IV Insulin
Patents will receive conventional IV insulin treatment with target glucose levels of 150-170 mg/dl
Drug: Conventional insulin treatment
All patients in the trial will have blood taken hourly for glucose analysis , regardless of their designated group. Adjustments of the insulin dose will be based on measurements of capillary blood glucose level.

Detailed Description:

Demographic data, social and medical histories, and clinical features at onset will be obtained via patient or family interview shortly after admission . We want to get the patients enrolled in our protocol as soon as possible because we believe that hyperglycemia levels greater than 200 mg/dl is a secondary insult that should be prevented as early as possible. However, a twelve-hour period after ICU admission is necessary for initial diagnosis and assessment of the patient's status in order to identify the patient as a potential study subject and to get consent from the patient's legal representative.

Within twelve hours of ICU admission, qualifying patients will be randomized one of the two groups. Randomization will be based on computer-generated codes that will be maintained in sequentially numbered opaque envelopes. The randomization will be stratified according to the severity of neurological injury based on GCS. The three stratification groups will be GCS=6-8, GCS=9-11 and GCS=12-14. Randomization will be done using random sized blocks within stratum, and patients will be randomized within stratum to either:

  1. Intensive intravenous insulin treatment (Target glucose levels of 80-110 mg/dl)
  2. Conventional intravenous insulin treatment (Target glucose levels of 150-170 mg/dl)

All patients in the trial will have blood taken hourly for glucose analysis, regardless of their designated group. Adjustments of the insulin dose will be based on measurements of capillary blood glucose level. The interval between the glucose samples will be increased when patients satisfy discharge criteria from the intensive care unit. The insulin dose adjustments will be made by a team of intensive care nurses, assisted by a study nurse who is not otherwise involved in the clinical care of the patients. RBC transfusions, if necessary, will be administered one unit at a time, and the patient's hemoglobin concentration will be measured before and after each transfusion.

All patients enrolled in the study will receive saline infusion supplemented with potassium. An orogastric or nasogastric feeding tube (Dobhoff tube) will be inserted. Enteral feeding will be started per feeding protocol with the goal of starting on day one. After insertion of a nasogastric or orogastric tube, tube position will be verified with abdominal x-ray. Enteral feeding will be instituted with 25 to 30 nonprotein kilocalories per kilogram of body weight per 24 hours and a balanced composition (including 0.13 to 0.26 g of nitrogen per kilogram per 24 hours and 20 to 40 percent of nonprotein in the form of lipids). 69 Formula used will be recorded. Patients will be fed continuously starting at a rate of 25 ml/hour. If continuous enteral feeding cannot be instituted or has to be stopped and enteral nutrition is anticipated to be interrupted for more than 7 days, total parenteral nutrition will be initiated. Patients will be allowed to progress to a regular oral diet after they have passed a swallowing study.

The underlying neurological conditions will be managed by the neurosurgical team according to the protocols of the Department of Neurosurgery of the University of Louisville.

When participating patients' physiological statuses have stabilized and the need for ICU monitoring and care is no longer necessary, they will be discharged to a lower level of care (in accordance with the 1999 guidelines of Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine). Upon discharge from ICU, patients in all groups will be treated with subcutaneous insulin according to established transition guidelines.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • non-traumatic SAH, ICH, or TBI
  • Glasgow Coma Scale between 6 and 14
  • admitted to an ICU of University of Louisville Hospital

Exclusion Criteria:

  • Patients <18 and >80 years
  • GCS Motor score <4 or an overall GCS score of 15
  • diabetic patients who suffer from dialysis-dependent diabetic nephropathy
  • patients with multiple injuries
  • patients who would have been classified as ASA 3 status prior to their acute neurological event
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01137773

Locations
United States, Kentucky
University of Louisville Hospital
Louisville, Kentucky, United States, 40202
Sponsors and Collaborators
University of Louisville
Investigators
Principal Investigator: Rainer Lenhardt, MD University of Louisville
  More Information

No publications provided

Responsible Party: University of Louisville
ClinicalTrials.gov Identifier: NCT01137773     History of Changes
Other Study ID Numbers: UofL IRB #562.06
Study First Received: June 3, 2010
Last Updated: November 12, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Louisville:
SAH (Subarachnoid Hemorrhage)
Brain Hemorrhage
Traumatic Brain Injury
SAH
ICH

Additional relevant MeSH terms:
Brain Injuries
Hemorrhage
Subarachnoid Hemorrhage
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014