A Randomized Controlled Trial of Glutamine Dipeptide in Severe Trauma

Critical Illness Clinical Trial

— GLND Trauma  

Official title:

A Randomized Controlled Trial of Glutamine Dipeptide in Severe Trauma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01776476
• Other study ID #: VR2278
• Secondary ID: UL1TR000445
• Status: Not yet recruiting
• Phase: Phase 2
• First received: January 17, 2013
• Last updated: January 22, 2013
• Start date: February 2013
• Est. completion date: February 2014

Study information

• Verified date: January 2013
• Source: Ziegler, Thomas R., M.D.
• Contact: Addison K May, MD FACS FCCM
• Phone: 615-936-7188
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find out if giving certain amino acids to critically injured patients can improve their condition or recovery, and lower their blood sugar and insulin needs. Amino acids are the 'building blocks' of proteins. The amino acid compound used in this study is called alanyl-glutamine dipeptide, also known as Dipeptiven® or glutamine. Glutamine is investigational, meaning not approved by the Food and Drug Administration (FDA) for intravenous use. However, it is approved by many countries in Europe, Asia and South America. Several studies suggest that giving glutamine has certain benefits in patients who need intensive care. In a study done at Emory University Medical Center using the same dose of glutamine, the number of hospital infections was lower in patients who had had cardiac, blood vessel or intestinal surgery compared to similar patients who received standard feedings without glutamine. No side effects were thought to be due to giving glutamine in that small study. This study is only being done at Vanderbilt University. The investigators plan to enroll 24 patients in the Trauma ICU over the next 12 months.

Description:

Design: Double-blind, randomized controlled trial of glutamine dipeptide given IV within the first 24 hours following severe trauma versus placebo for 7 days.

Primary Aim: To assess IR, patients will undergo EHC on study day 2 and 7 or day of discharge from ICU.

Secondary Aims: Near continuous data capture of glycemic control via CPOE system will be assessed for surrogate measures of IR. Other laboratory endpoints that may serve as biomarkers of the stress response will be collected daily to day 7. Patients will be followed for mortality and infectious morbidity for 28 days or until hospital discharge.

Inclusion and Exclusion Criteria:

To ensure that the injured patient cohort identified for entry is at sufficient risk for the development of organ dysfunction, infectious complications, and death, while surviving in the ICU for 5 days or longer, the investigators analyzed patient visits to VUMC to identify entry criteria that provided roughly 20% mortality with appropriate length of stay. Enrollment criteria include:

• Severe trauma (ISS > 16)

• Mechanical ventilation

• Either blood transfusion or inotropic support prior to enrollment.

• No prior history of diabetes Enrollment Goals: A total of 24 subjects in this trial at Vanderbilt University Medical Center.

Subject identification: All mechanically ventilated, adult patients admitted directly to the Trauma ICU will be screened for appropriate ISS, transfusion need, and inotropic support within the first 24 hrs of admission.

Informed consent and subject enrollment: If the patient meets inclusion and exclusion criteria, the subject's legally authorized representative (LAR) will be approached for consent for trial participation.

Randomization of study subjects: Patients will be randomized in blocks to receive either placebo or IV glutamine dipeptide (1:1) using a computerized randomization algorithm. Solutions will be prepared by an unblinded pharmacist and placed in identical infusion bags; study and placebo solutions will have identical appearance and smell.

Study Measurements: Surrogate measures of IR will include: mean serum glucose, insulin requirement on standard glycemic control protocol, serum insulin, C-peptide, adiponectin, glutamine and isoprostane levels each standardized to individual patient nutritional provision throughout the ICU stay. Biomarkers of the physiologic stress response and their recovery include TNF, IL-6, IL-8 and estradiol.

Clinical Data from Medical Record: Clinical data will be obtained during the course of standard care. All data is maintained in an electronic medical record and electronic data repository. Discrete data points will be validated at the point of entry and captured prospectively.

Clinical Endpoints: Patients will be followed for 28 days or until hospital discharge to assess for patient survival and for infectious complications. Infections will be defined using CDC definitions. For ventilated patients, quantitative bronchoscopic alveolar lavage will be performed except where contraindicated. Patients will be assessed daily until discharge and at day 28 for infections and survival. Daily SOFA scores will be captured from admission until day 7 or discharge from the ICU.

Safety: This study has been approved by the Institutional Review Board and will adhere to the regulations for the protection of human subjects. GlnD has been approved in Europe for intravenous use and has been extensively studied in critically ill populations. All other measurements, other than the EHC are obtained through processes that are standard of care. Blood samples obtained daily will be less than 10 mL and will not pose more than minimal risk. Glycemic management is provided as a standard of care and has been documented to be safe and effective at the investigators institution with blood glucoses obtained every 2 hours. During the euglycemic, hyperinsulinemic clamp, blood glucose is controlled by altering glucose provision rather than insulin rate. This allows more rapid and precise adjustments. Measurements are obtained much more frequently than during standard processes. These methods have previously been validated for safety in the literature and patients are intensively monitored during the test.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: February 2014
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Severe trauma (ISS > 16) no more than 24 hours prior to initiation of study drug

2. Mechanical Ventilation

3. Blood transfusion OR inotropic support prior to enrollment

4. Estimated BMI <40.0 kg/m2

Exclusion Criteria:

1. Moribund patients, unlikely to survive 24 hours

2. Anticipated ICU stay < 48 hours

3. Pre-existing diabetes mellitus

4. Known allergy to the drug or any components

5. Known pregnancy

6. Corticosteroid administration prior to enrollment

7. Severe traumatic brain injury or uncontrolled intracranial hypertension

8. Current malignancy

9. History of seizures, chronic liver disease, chronic renal failure requiring dialysis or solid organ transplantation

10. Known HIV/AIDS

11. Known treatment with another investigational product within 30 days

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Critical Illness
• Hyperglycemia
• Insulin Resistance
• Stress Hyperglycemia
• Trauma
• Wounds and Injuries

Intervention

Drug:
• Glutamine
Glutamine dipeptide 0.5 gm/kg/day will be administered as a continuous infusion over 24 hours for up to 7 days or ICU discharge, whichever comes first.

Other:
• Placebo
normal saline of equivalent volume to the experimental drug infusion administered as a continuous infusion over 24 hours for up to 7 days or ICU discharge, whichever comes first

Procedure:
• Surgery

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Ziegler, Thomas R., M.D.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mortality		Day 1-day 30	Yes
Primary	Change of insulin resistance by euglycemic hyperinsulinemic clamp		Day 2 and Day 7	No
Secondary	Surrogate measures of glucose metabolism	Blood glucose, insulin infusion rate, mean kcal of glycemic provision, insulin multiplier	Day 1-Day 30	No