Trial record 3 of 18 for:    Therapeutic Hypothermia | Exclude Unknown | updated from 06/01/2013 to 12/18/2013

Intestinal Ischemia as a Stimulus for Systemic Inflammatory Response After Cardiac Arrest (TICA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Virginia Commonwealth University
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT01944605
First received: September 12, 2013
Last updated: September 12, 2013
Last verified: September 2013
  Purpose

Out-of-hospital cardiac arrest (CA) is a leading public health problem causing nearly one third of a million deaths annually in the US, accounting for half of all cardiovascular deaths and surpassing deaths from stroke, heart failure, and breast and lung cancer combined. Twenty to fifty percent of CA patients (pts) can be resuscitated initially but many die before hospital discharge or suffer permanent neurologic damage. Therapeutic hypothermia (TH) improves survival and neurological outcomes. Despite aggressive, targeted post arrest management, including TH, approximately 50% of pts die before leaving the hospital due to global ischemia-reperfusion injury (IRI) known as the "post arrest syndrome", 1 which is a sepsis-like state characterized by elevated markers of cellular inflammation and injury. It is believed that TH works by decreasing the body's basal metabolic rate (BMR) and attenuating the systemic inflammatory response (SIR). However, specific triggers of the intense pro-inflammatory response are unclear. This "gap" in knowledge must be closed to identify targeted therapy to decrease IRI and improve outcomes.

Blood flow to the gut is decreased markedly and intestinal tissue becomes ischemic during CA and CPR, particularly when vasoconstrictor drugs such as epinephrine, are given. IRI of the intestine increases intestinal permeability leading to intestinal microbial translocation and endotoxin release that can stimulate and perpetuate systemic inflammation and cause subsequent multi-organ dysfunction. Endotoxin also increases body temperature and energy expenditure and may attenuate TH induced reductions in BMR and hence, decrease efficacy. The purpose of this novel pilot study is to detect systemic endotoxin release following CA in humans and determine association with cytokine activation, and BMR alterations during TH.


Condition
Cardiac Arrest
Reperfusion Injury

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Intestinal Ischemia as a Stimulus for Systemic Inflammatory Response After Cardiac Arrest

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • Detection of Endotoxin Activity [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Endotoxin activity will be measured by the Endotoxin Activity Assay and values . of >0.4 EA units will be used as the "cut-off" for the presence of pathological endotoxin.


Secondary Outcome Measures:
  • Detection of sCD14 [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    To demonstrate activation of endotoxin by the immune system and "upstream" physiologic changes necessary for systemic endotoxemia to occur

  • Detection of stool lactoferrin and stool α1-antitrypsin [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    To demonstrate evidence of intestinal inflammation and permeability that can lead to endotoxemia and "downstream" cellular inflammatory responses responsible for end organ damage

  • Detection and quantification of inflammatory cytokines [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    To demonstrate an association with the primary outcome

  • BMR measurement elevation [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    To determine its association with endotoxemia and cytokine. BMR is being measured to determine if pts with higher levels of endotoxin and cytokines have higher BMR and therefore blunted therapeutic value of TH


Biospecimen Retention:   Samples Without DNA

Blood plasma Blood serum Whole blood Stool Expired Gas


Estimated Enrollment: 40
Study Start Date: September 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Cardiac Arrest patients undergoing Therapeutic Hypothermia
Cardiac Arrest subjects with Return Of Spontaneous Circulation (ROSC) and undergoing treatment with Therapeutic Hypothermia will undergo sampling of blood, stool, and expired gas data at physiologically predetermined time points.

Detailed Description:

Hypothesis 1 Intestinal ischemia during and following Caridac Arrest leads to increased gut permeability and endotoxin release that stimulates the Systemic Inflammatory Response that is responsible for subsequent death and disability after resuscitation.

Hypothesis 2: Different degrees of systemic endotoxin activity variably affect Basic Metabolic Rate during Therapeutic Hypothermia

Serial samples of blood, stool and expired gas will be measured at predetermined timepoints after ROSC from cardiac arrest.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

All adult patients resuscitated from Cardiac Arrest successfully and undergoing therapeutic hypothermia will be evaluated for potential inclusion

Criteria

Inclusion Criteria:

Adult, Cardiac Arrest with ROSC receiving Therapeutic Hypothermia-

Exclusion Criteria:

  • Age < 18
  • Cardiac Arrest of traumatic etiology
  • Known to be pregnant
  • Prisoner
  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: NCT01944605

Contacts
Contact: Debra Spillman 804-828-2692 dspillman@mcvh-vcu.edu

Locations
United States, Virginia
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Mary Ann Peberdy, MD    804-828-4571    mpeberdy@aol.com   
Principal Investigator: Mary Ann Peberdy, MD         
Sub-Investigator: Joseph Ornato, MD         
Sub-Investigator: Renee Reid, MD         
Sub-Investigator: Harinder DHindsa, MD         
Sub-Investigator: Charlotte Roberts, ACNP         
Sub-Investigator: Puneet Puri, MD         
Sub-Investigator: Arun Sanyal, MD         
Sub-Investigator: Antonio Abbate, MD         
Sub-Investigator: Veronica Sikka, MD         
Sponsors and Collaborators
Virginia Commonwealth University
American Heart Association
Investigators
Principal Investigator: Mary Ann Peberdy, M.D. Virginia Commonwealth University
  More Information

No publications provided

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT01944605     History of Changes
Other Study ID Numbers: HM15326
Study First Received: September 12, 2013
Last Updated: September 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Virginia Commonwealth University:
Endotoxin
Cytokine
Metabolism

Additional relevant MeSH terms:
Heart Arrest
Reperfusion Injury
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Postoperative Complications
Vascular Diseases

ClinicalTrials.gov processed this record on July 05, 2015