L-Carnitine Administration in Early Sepsis

Sepsis is a severe and overwhelming response to an infection in the body. Over 750,000 patients in the United States develop sepsis every year. As sepsis becomes progressively more severe, a patient's blood pressure drops to dangerous levels and the body cannot pump oxygen to the rest of the body, which is necessary for normal cell function. This is called septic shock. When someone develops septic shock, it is very common for the smallest blood vessels in the body called the microcirculation to clog, like a highway during rush hour. Even with the best medical care, more than one in three patients with septic shock will die.

The major goal of this study is to test if intravenous replacement of a naturally occurring nutrient that is lost by the body during sepsis called L-carnitine can reduce how sick a patient with sepsis becomes. In our study, some patients will receive L-carnitine and others will receive saline. We will measure markers determining severity of illness in both groups and compare them to see if L-carnitine helps patients get better faster. Based on research already conducted, we believe L-carnitine will improve blood flow in the microcirculation, delivering more oxygen to cells, and help the body get better. To test if this is true, we will directly look at the microcirculation under the tongue with a special magnifying camera that looks at red blood cells, and compare both groups.

Study Overview

• Status: Terminated
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Normal Saline; Drug: L-Carnitine

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Suspected or confirmed infection
• Any two of four criteria of systemic inflammatory response
• Requirement for vasopressors to treat shock
• Enrollment within 12 hours of vasopressor initiation
• SOFA score of greater than or equal to 5 at the time of enrollment

Exclusion Criteria:

• Age <18 years
• Pregnancy or breastfeeding
• Any primary diagnosis other than sepsis
• Established Do Not Resuscitate status or advanced directives restricting aggressive care or treating physician deems aggressive care unsuitable
• Any history of seizures or a known seizure disorder
• Any known inborn error of metabolism
• Anticipated requirement for surgery that would interfere with the 12 hour infusion time
• Active participation in another interventional study
• Inability to obtain informed consent
• Cardiopulmonary resuscitation (chest compression or defibrillation) prior to enrollment
• Known systemic allergy to carnitine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline	Drug: Normal Saline; Bolus followed by 1 L NS infusion over 12 hours.
Experimental: L-Carnitine	Drug: L-Carnitine; 4 gram bolus followed by 8 gram in 1 L NS infused over 12 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in organ failure	SOFA score will be measured at 0 and 24 hours	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality		3 months
All-cause mortality		6 months
All-cause mortality		12 months
Microcirculation	Test if carnitine improves blood flow in the sublingual microvasculature during septic shock by performing sidestream dark-field (SDF) video-microscopy of the sublingual microcirculation, prior to and after 12 hours of carnitine infusion.	12 hours
ICU and hospital length of stay		Duration of stay
All-cause mortality		28 day
Change in inflammatory markers	Assess change in various inflammatory markers over predefined time points.	12 hours
Change in inflammatory markers	Assess change in various inflammatory markers over predefined time points.	24 hours
Change in inflammatory markers	Assess change in various inflammatory markers over predefined time points.	48 hours

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Alan E Jones, MD, University of Mississippi and Carolinas Medical Center, Department of Emergency Medicine

Publications and helpful links

General Publications

• Puskarich MA, Shapiro NI, Massey MJ, Kline JA, Jones AE. Lactate Clearance in Septic Shock Is Not a Surrogate for Improved Microcirculatory Flow. Acad Emerg Med. 2016 Jun;23(6):690-3. doi: 10.1111/acem.12928. Epub 2016 May 11.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: August 30, 2010
• First Submitted That Met QC Criteria: September 1, 2010
• First Posted (Estimate): September 2, 2010

Study Record Updates

• Last Update Posted (Actual): April 22, 2022
• Last Update Submitted That Met QC Criteria: April 14, 2022
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Shock; Sepsis; Carnitine
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis
• Other Study ID Numbers: 04-10-06A; 10POST3560001 (Other Grant/Funding Number: American Heart Association)