Brain InjuriesPhase 4NCT02161055
Intensive Versus Nonintensive Insulin Therapy for Hyperglycemia After Traumatic Brain Injury
A Phase 4 study testing Insulin in people with Brain Injuries and Hyperglycemia, run by Lianyungang Oriental Hospital at 2 sites in China.
Trial summary
An increase in blood glucose is a common clinical symptom in patients following traumatic brain injury. Studies confirm that death after traumatic brain injury was not only associated with nerve injury, but also correlated with abnormal physiological and metabolic reactions. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Brain Injuries, Hyperglycemia
- What is being tested?
- Insulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 2 sitesChina
- Study dates
- Jun 2014to Dec 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Severe closed traumatic brain injury diagnosed in the clinic;
- Severe closed traumatic brain injury verified by CT examinations;
- Patients who are in accordance with the indications of craniotomy for severe traumatic brain injury;
- Blood glucose levels > 7.0 mmol/L measured twice by rapid examination within 2 hours of hospital admission;
- Glasgow coma score between 3 and 8;
- At the age of 18 - 80 years old;
- Irrespective of gender.
Who cannot join
- At the age of < 18 years old or > 80 years old;
- Glasgow coma score > 8;
- Patients combined with multiple site damage;
- Hemodialysis-dependent patients combined with diabetic nephropathy;
- Patients with nervous system disease before traumatic brain injury;
- Patients with a history of diabetes before suffering from a traumatic brain injury.
Trial locations and contacts
2 sites in 1 country.
China2 sites, 2 recruiting
- Recruiting
Lianyungang Oriental Hospital
Lianyungang, Jiangsu, 222042
Wenxue Wang, M.D., Ph.D., +8615151268106, 731545804@qq.com
Wenxue Wang, M.D., Ph.D.
- Recruiting
The First People's Hospital of Lianyungang
Lianyungang, Jiangsu
Aimin Li, M.D.
Aimin Li, M.D.
About this study
Official title: Randomized Controlled Clinical Study of Intensive Versus Nonintensive Insulin Therapy for Hyperglycemia After Traumatic Brain Injury
An increase in blood glucose is a common clinical symptom in patients following traumatic brain injury. Studies confirm that death after traumatic brain injury was not only associated with nerve injury, but also correlated with abnormal physiological and metabolic reactions. Hyperglycemia is a manifestation of physiological and metabolic disorders after traumatic brain injury. Traumatic brain injury induced hyperglycemia, and then aggravated secondary injury to the brain. Therefore, it is of important clinical significance to study the treatment of hyperglycemia after traumatic brain injury.
Read the detailed description
Hyperglycemia induced by traumatic brain injury is directly correlated with patient prognosis. Previous studies showed that if blood glucose could be controlled < 6.11 mmol/L, prognosis would be good and mortality would be decreased by approximately 50%. Moreover, the incidence of ICU-related complications, especially infection, was obviously reduced. A study concerning severe traumatic brain injury analyzed the recovery of patients at 18 days, 3 months and 1 year after trauma, and demonstrated that the prognosis of patients with blood glucose levels < 11.1 mmol/L within 24 hours of hospital admission was apparently better than those whose blood glucose levels were > 11.1 mmol/L. Hyperglycemia occurred after traumatic brain injury and was treated with intensive insulin therapy. Thus, blood glucose levels were controlled between 4.4 and 6.1 mmol/L, which noticeably shortened insulin use and decreased the incidence of multiple organ dysfunction and mortality of patients with traumatic brain injury.
It is well known that hyperglycemia will appear after traumatic brain injury. However, there are few clinical studies addressing continuous dynamic monitoring of blood glucose of traumatic brain injury patients and the relationship between changes in blood glucose and the degree of traumatic brain injury. Insulin therapy for reducing injury to secondary nerve cells after traumatic brain injury and for improving functional prognosis has also not been explored.
When blood glucose level is > 7.0 mmol/L as measured twice by rapid examination within 2 hours of hospital admission, patients with hyperglycemia after severe closed traumatic brain injury will be randomly divided into the intensive therapy group and nonintensive therapy group according to the random number table.
Patients in both groups will be treated using the protocol as follows.
- Craniotomy for traumatic brain injury to mainly decompress and remove hematoma. Standard trauma craniotomy and incision of trachea will be performed.
- During the operation, all patients will undergo ventricular puncture. Cerebrospinal fluid will be obtained for biochemical analysis and cell culture.
- All patients will be closely monitored in the ICU of the Department of Neurosurgery.
- Therapeutic protocols for severe traumatic brain injury will be used.
- Glucocorticoid can cause disorders of glucose metabolism, so glucocorticoids can not be regularly applied in these two groups.
- When glucose was injected into the vein, insulin was added at the proportion of 5:1 to eliminate glucose effects on blood glucose.
Blood glucose measurement: Capillary blood will be obtained from the tip of the ring finger to measure blood glucose. For a period, the blood should be collected from the same finger to make sure an accurate measurement occurs. When blood glucose of a patient undergoing transfusion was measured, blood should be collected from the tip of the finger of the limb without transfusion to ensure the accuracy of measurement.
Monitoring of target blood glucose: insulin dose will be selected in accordance with the Yale Insulin Infusion Protocol.
- Insulin will be infused into the vein using a micropump at 0.1 μ/kg•h;
- When blood glucose levels are > 20.0 mmol/L, insulin will be infused at 10.0 μ/h;
- When blood glucose levels are between 17.1 and 20.0 mmol/L, insulin will be infused at 8.0 μ/h;
- When blood glucose levels are between 14.1 and 17.0 mmol/L, insulin will be infused at 6.0 μ/h;
- When blood glucose levels are between 11.5 and 14.0 mmol/L, insulin will be infused at 4.0 μ/h;
- Within 12 and 24 hours, blood glucose levels will be maintained within the range of target blood glucose. During this period, blood glucose levels will be monitored once every 2 hours, and insulin dose will be adjusted in time.
- If blood glucose levels are higher than the target value, insulin dose could be gradually increased by 1-2 μ/h;
- When blood glucose levels reach the target value, insulin dose could be gradually diminished until terminated.
- Conditions
- Brain Injuries, Hyperglycemia
- Being tested
- Insulin
- Keywords
- Insulin, Hyperglycemia, Postoperative Mortality, Intensive insulin therapy, Non-intensive insulin therapy, Brain Injuries, Wounds and Injuries, Craniocerebral Trauma, Trauma, Nervous System
- Medical subject headings
- Brain Injuries, Hyperglycemia, Insulin Resistance, Wounds and Injuries, Craniocerebral Trauma, Trauma, Nervous System
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InsulinDrug
Also called Insulin Injection(10mL:400u), manufactured by Wanbang Biochemical Pharmaceutical Co., Ltd. Lot No. 1307230, No. 1302225, No. 1307210.
Insulin dose was selected in accordance with the Yale Insulin Infusion Protocol.
- Amount of insulin (u) = [fasting blood glucose (mmol/L) × 18-100] × 10 × body weight (kilogram) × 0.6 ÷ 1000 ÷ 2
| Study group | Role | What they receive |
|---|---|---|
| Strict control group | Experimental | Intensive insulin therapy: Keep Target blood glucose levels between 4.4-7.0 mmol/L;
Blood glucose levels were monitored and controlled using the Yale Insulin Infusion Protocol. Rapid blood glucose levels were monitored once every 2 hours. Receives: Drug: Insulin |
| Moderate control group | Experimental | Intensive insulin therapy: Keep target blood glucose levels between 7.1 and 10.0 mmol/L.
Blood glucose levels were monitored and controlled using the Yale Insulin Infusion Protocol. Rapid blood glucose levels were monitored once every 2 hours Receives: Drug: Insulin |
| Slight control group | Experimental | Intensive insulin therapy: Keep target blood glucose levels between 10.1 and 13.0 mmol/L.
Blood glucose levels were monitored and controlled using the Yale Insulin Infusion Protocol. Rapid blood glucose levels were monitored once every 2 hours. Receives: Drug: Insulin |
| Non-intensive insulin therapy | Active comparator | Rapid blood glucose levels were measured once every 2 hours. When blood glucose levels were ≤ 13.0 mmol/L, no intervention was performed; When blood glucose levels were > 13.0 mmol/L, regular insulin was subcutaneously injected separately. During fasting, insulin was injected once every 8 hours. During venous or enteral nutrition infusion, insulin was infused at 30 minutes before nutrition infusion. When blood glucose levels were ≤ 13.0 mmol/L, insulin infusion was terminated. Receives: Drug: Insulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Monitoring of target blood glucose
Within 1 week of hospitalization, rapid blood glucose levels will be recorded once every 2 hours in each group. Glycosylated serum protein levels will be measured once a week, for 4 consecutive weeks. This index reflects the mean blood glucose levels of 2 - 3 weeks.
Measured: 4 weeks
Secondary outcomes (2)
Mortality
Percentage of patients who die during hospitalization period, at 1 week after surgery, at 2 weeks after surgery, and at 3 months after injury.
Measured: 6 months after surgery
Evaluation of activity of daily living
At 2 weeks after hospital admission, Modified Rankin Scale and Glasgow outcome score will be applied.
During follow-up at 3 months after injury, Barthel index, Glasgow outcome score and Modified Rankin Scale will be employed.
During follow-up at 6 months after injury, Barthel index and Glasgow outcome score will be used.
Measured: 2 weeks after hospital admission, 3 months and 6 months after injury
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2014 (estimated)
- Study startJun 2014
- Primary completionJun 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain InjuriesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 144 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lianyungang Oriental Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The First People's Hospital of Lianyungang
- Responsible party
- Principal investigator, Wenxue Wang, Lianyungang Oriental Hospital
- Investigators
- Wenxue Wang, M.D., Ph.D., Principal investigator, Lianyungang Oriental Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02161055
- Sponsor's protocol ID
- LYG-1401-WW
- Status last verified
- Jul 2014
- First submitted
- 5 Jun 2014
- Last updated
- 23 Jul 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Yuan T, He H, Liu Y, Wang J, Kang X, Fu G, Xie F, Li A, Chen J, Wang W. Association between blood glucose levels and Glasgow Outcome Score in patients with traumatic brain injury: secondary analysis of a randomized trial. Trials. 2022 Jan 15;23(1):38. doi: 10.1186/s13063-022-06005-5.
PubMed 35033158
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Clinical Study of Intensive Versus Nonintensive Insulin Therapy for Hyperglycemia After Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT02161055
- Acronym / sponsor ID
- LYG-1401-WW
- Conditions
- Brain Injuries, Hyperglycemia
- Keywords
- Insulin, Hyperglycemia, Postoperative Mortality, Intensive insulin therapy, Non-intensive insulin therapy, Brain Injuries, Wounds and Injuries, Craniocerebral Trauma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 144 participants (estimated)
- Lead sponsor
- Lianyungang Oriental HospitalUniversity, hospital or other
- Collaborators
- The First People's Hospital of Lianyungang
- Study start
- Jun 2014
- Primary completion
- Jun 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 11 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An increase in blood glucose is a common clinical symptom in patients following traumatic brain injury. Studies confirm that death after traumatic brain injury was not only associated with nerve injury, but also correlated with abnormal physiological and metabolic reactions. Hyperglycemia is a manifestation of physiological and metabolic disorders after traumatic brain injury. Traumatic brain injury induced hyperglycemia, and then aggravated secondary injury to the brain. Therefore, it is of important clinical significance to study the treatment of hyperglycemia after traumatic brain injury.
Detailed description
Hyperglycemia induced by traumatic brain injury is directly correlated with patient prognosis. Previous studies showed that if blood glucose could be controlled < 6.11 mmol/L, prognosis would be good and mortality would be decreased by approximately 50%. Moreover, the incidence of ICU-related complications, especially infection, was obviously reduced. A study concerning severe traumatic brain injury analyzed the recovery of patients at 18 days, 3 months and 1 year after trauma, and demonstrated that the prognosis of patients with blood glucose levels < 11.1 mmol/L within 24 hours of hospital admission was apparently better than those whose blood glucose levels were > 11.1 mmol/L. Hyperglycemia occurred after traumatic brain injury and was treated with intensive insulin therapy. Thus, blood glucose levels were controlled between 4.4 and 6.1 mmol/L, which noticeably shortened insulin use and decreased the incidence of multiple organ dysfunction and mortality of patients with traumatic brain injury.
It is well known that hyperglycemia will appear after traumatic brain injury. However, there are few clinical studies addressing continuous dynamic monitoring of blood glucose of traumatic brain injury patients and the relationship between changes in blood glucose and the degree of traumatic brain injury. Insulin therapy for reducing injury to secondary nerve cells after traumatic brain injury and for improving functional prognosis has also not been explored.
When blood glucose level is > 7.0 mmol/L as measured twice by rapid examination within 2 hours of hospital admission, patients with hyperglycemia after severe closed traumatic brain injury will be randomly divided into the intensive therapy group and nonintensive therapy group according to the random number table.
Patients in both groups will be treated using the protocol as follows.
- Craniotomy for traumatic brain injury to mainly decompress and remove hematoma. Standard trauma craniotomy and incision of trachea will be performed.
- During the operation, all patients will undergo ventricular puncture. Cerebrospinal fluid will be obtained for biochemical analysis and cell culture.
- All patients will be closely monitored in the ICU of the Department of Neurosurgery.
- Therapeutic protocols for severe traumatic brain injury will be used.
- Glucocorticoid can cause disorders of glucose metabolism, so glucocorticoids can not be regularly applied in these two groups.
- When glucose was injected into the vein, insulin was added at the proportion of 5:1 to eliminate glucose effects on blood glucose.
Blood glucose measurement: Capillary blood will be obtained from the tip of the ring finger to measure blood glucose. For a period, the blood should be collected from the same finger to make sure an accurate measurement occurs. When blood glucose of a patient undergoing transfusion was measured, blood should be collected from the tip of the finger of the limb without transfusion to ensure the accuracy of measurement.
Monitoring of target blood glucose: insulin dose will be selected in accordance with the Yale Insulin Infusion Protocol.
- Insulin will be infused into the vein using a micropump at 0.1 μ/kg•h;
- When blood glucose levels are > 20.0 mmol/L, insulin will be infused at 10.0 μ/h;
- When blood glucose levels are between 17.1 and 20.0 mmol/L, insulin will be infused at 8.0 μ/h;
- When blood glucose levels are between 14.1 and 17.0 mmol/L, insulin will be infused at 6.0 μ/h;
- When blood glucose levels are between 11.5 and 14.0 mmol/L, insulin will be infused at 4.0 μ/h;
- Within 12 and 24 hours, blood glucose levels will be maintained within the range of target blood glucose. During this period, blood glucose levels will be monitored once every 2 hours, and insulin dose will be adjusted in time.
- If blood glucose levels are higher than the target value, insulin dose could be gradually increased by 1-2 μ/h;
- When blood glucose levels reach the target value, insulin dose could be gradually diminished until terminated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Strict control group | Experimental | Drug: InsulinIntensive insulin therapy: Keep Target blood glucose levels between 4.4-7.0 mmol/L; Blood glucose levels were monitored and controlled using the Yale Insulin Infusion Protocol. Rapid blood glucose levels were monitored once every 2 hours. |
| Moderate control group | Experimental | Drug: InsulinIntensive insulin therapy: Keep target blood glucose levels between 7.1 and 10.0 mmol/L. Blood glucose levels were monitored and controlled using the Yale Insulin Infusion Protocol. Rapid blood glucose levels were monitored once every 2 hours |
| Slight control group | Experimental | Drug: InsulinIntensive insulin therapy: Keep target blood glucose levels between 10.1 and 13.0 mmol/L. Blood glucose levels were monitored and controlled using the Yale Insulin Infusion Protocol. Rapid blood glucose levels were monitored once every 2 hours. |
| Non-intensive insulin therapy | Active comparator | Drug: InsulinRapid blood glucose levels were measured once every 2 hours. When blood glucose levels were ≤ 13.0 mmol/L, no intervention was performed; When blood glucose levels were > 13.0 mmol/L, regular insulin was subcutaneously injected separately. During fasting, insulin was injected once every 8 hours. During venous or enteral nutrition infusion, insulin was infused at 30 minutes before nutrition infusion. When blood glucose levels were ≤ 13.0 mmol/L, insulin infusion was terminated. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Severe closed traumatic brain injury diagnosed in the clinic;
- Severe closed traumatic brain injury verified by CT examinations;
- Patients who are in accordance with the indications of craniotomy for severe traumatic brain injury;
- Blood glucose levels > 7.0 mmol/L measured twice by rapid examination within 2 hours of hospital admission;
- Glasgow coma score between 3 and 8;
Key exclusion criteria (6 listed)
- At the age of < 18 years old or > 80 years old;
- Glasgow coma score > 8;
- Patients combined with multiple site damage;
- Hemodialysis-dependent patients combined with diabetic nephropathy;
- Patients with nervous system disease before traumatic brain injury;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InsulinAlso: Insulin Injection(10mL:400u), manufactured by Wanbang Biochemical Pharmaceutical Co., Ltd. Lot No. 1307230, No. 1302225, No. 1307210.Insulin dose was selected in accordance with the Yale Insulin Infusion Protocol. • Amount of insulin (u) = [fasting blood glucose (mmol/L) × 18-100] × 10 × body weight (kilogram) × 0.6 ÷ 1000 ÷ 2 | Drug | Moderate control group, Non-intensive insulin therapy, Slight control group, Strict control group |
Primary outcome
Monitoring of target blood glucose
Time frame: 4 weeks
Within 1 week of hospitalization, rapid blood glucose levels will be recorded once every 2 hours in each group. Glycosylated serum protein levels will be measured once a week, for 4 consecutive weeks. This index reflects the mean blood glucose levels of 2 - 3 weeks.
2 secondary outcomes
Mortality
Time frame: 6 months after surgery
Evaluation of activity of daily living
Time frame: 2 weeks after hospital admission, 3 months and 6 months after injury
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2014.
- Derived from this study: PubMed 35033158Yuan T, He H, Liu Y, Wang J, Kang X, Fu G, Xie F, Li A, Chen J, Wang W. Association between blood glucose levels and Glasgow Outcome Score in patients with traumatic brain injury: secondary analysis of a randomized trial. Trials. 2022 Jan 15;23(1):38. doi: 10.1186/s13063-022-06005-5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wenxue Wang, M.D., Ph.D. principal investigator
Lianyungang Oriental Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Insulin in people with Brain Injuries and Hyperglycemia, run by Lianyungang Oriental Hospital at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wenxue Wang, M.D., Ph.D. (+8615151268106, 731545804@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Monitoring of target blood glucose (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02161055, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2014.