Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 25 of 51 for:    TIMP2

Effects of Oxygen Treatment on Mechanisms Involved in Ischemia-reperfusion Injury: A Pilot Study in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02286544
Recruitment Status : Completed
First Posted : November 10, 2014
Last Update Posted : December 11, 2017
Sponsor:
Collaborator:
University Hospital, Linkoeping
Information provided by (Responsible Party):
Leif Svensson, Karolinska Institutet

Brief Summary:

Oxygen treatment is widely used in acutely ill patients. In particular, oxygen treatment is routinely used in acute coronary syndrome (ACS) patients with suspected acute myocardial infarction and variably recommended in ACS-guidelines, despite very limited data supporting a beneficial effect.

Immediate re-opening of the acutely occluded infarct-related bloodvessel via primary percutaneous coronary intervention (PCI) is the treatment of choice to limit ischemic injury in the setting of ST-elevation ACS (STE-ACS). However, the sudden re-initiation of blood flow achieved with primary PCI can give rise to further damage, so-called reperfusion injury. Ischemia and reperfusion associated myocardial injury (IR-injury) involves a wide range of pathological processes. Vascular leakage, activation of cell death programs, transcriptional reprogramming, no reflow phenomenon and innate and adaptive immune activation all contribute to tissue damage, thereby determining the infarct size. The effect of oxygen treatment on these pathological processes, on the extent of IR-injury and the final infarct size in STE-ACS patients has not previously been studied.

ACS is characterized by a systemic inflammation with typical elevations of soluble inflammatory markers as well as changes in white blood cells. The inflammatory reaction might be considered helpful in restoring myocardial tissue structure and function, but on the other hand it might worsen IR-injury by activating various pathological processes. In human experimental studies, Salmonella typhi vaccine has been used to create a standardized model of systemic inflammation and when administered to healthy volunteers the vaccination has not been associated with any adverse events.

In an ongoing register randomized multicentre clinical trial, the DETO2X (Determination of role of oxygen in suspected acute myocardial infarction) study, the effect of oxygen on morbidity and mortality in ACS patients is being investigated. In a substudy of the DETO2X-trial, the investigators have planned to evaluate the effect of oxygen treatment on IR-injury in STE-ACS as assessed by biomarkers reflecting various aspects of the pathological processes involved.

The presented study is an experimental pilot study performed in healthy volunteers with a Salmonella typhi vaccine-induced inflammation with the purpose of studying effects of oxygen treatment on biological systems involved in the pathogenesis of IR- injury.


Condition or disease Intervention/treatment Phase
Myocardial Infarction Inflammation Acute Coronary Syndrome (ACS) Reperfusion Injury Biological: Salmonella typhi vaccine (Typhim Vi®) Drug: Oxygen (Oxymask®) Drug: Atorvastatin Phase 1

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Oxygen Treatment on Mechanisms Involved in Ischemia-reperfusion Injury: A Single Center, Randomized, Controlled Pilot Study in Healthy Volunteers
Actual Study Start Date : October 2014
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Oxygen Therapy

Arm Intervention/treatment
Active Comparator: Salmonella typhi vaccine
0.5 mL Salmonella typhi vaccine
Biological: Salmonella typhi vaccine (Typhim Vi®)
A peripheral venous catheter will be inserted. This catheter will be used to collect blood sample during the study day. In addition, peripheral oxygen saturation will be measured by pulse oximetry. After baseline venous blood samples have been collected, all study participants will receive 0.5 mL of the Salmonella typhi vaccine as an intramuscular injection (Typhim Vi®, Sanofi Pasteur MSD, injection solution 25 microgram/0.5 mL) Venous blood samples will be collected at 3, 6 and 8 hours after baseline. After the 8-hour blood sampling, the peripheral venous catheter will be removed and the study day ended.

Experimental: Salmonella typhi vaccine + oxygen
0.5 mL Salmonella typhi vaccine + 6l/min oxygen
Biological: Salmonella typhi vaccine (Typhim Vi®)
A peripheral venous catheter will be inserted. This catheter will be used to collect blood sample during the study day. In addition, peripheral oxygen saturation will be measured by pulse oximetry. After baseline venous blood samples have been collected, all study participants will receive 0.5 mL of the Salmonella typhi vaccine as an intramuscular injection (Typhim Vi®, Sanofi Pasteur MSD, injection solution 25 microgram/0.5 mL) Venous blood samples will be collected at 3, 6 and 8 hours after baseline. After the 8-hour blood sampling, the peripheral venous catheter will be removed and the study day ended.

Drug: Oxygen (Oxymask®)

As in arm 1. Half an hour after vaccination is administered, oxygen treatment will be initiated at 6 L/min via Oxymask® and continued for 6 hours. During oxygen treatment peripheral oxygen saturation will be measured by pulsoximetry.

Venous blood samples will be collected at 3, 6 and 8 hours after baseline. After the 8-hour blood sampling, the peripheral venous catheter will be removed and the study day ended.


Experimental: S. typhi vaccine + oxygen + Atorvastatin
0.5 mL Salmonella typhi vaccine + 6l/min oxygen + 80mg Atorvastatin
Biological: Salmonella typhi vaccine (Typhim Vi®)
A peripheral venous catheter will be inserted. This catheter will be used to collect blood sample during the study day. In addition, peripheral oxygen saturation will be measured by pulse oximetry. After baseline venous blood samples have been collected, all study participants will receive 0.5 mL of the Salmonella typhi vaccine as an intramuscular injection (Typhim Vi®, Sanofi Pasteur MSD, injection solution 25 microgram/0.5 mL) Venous blood samples will be collected at 3, 6 and 8 hours after baseline. After the 8-hour blood sampling, the peripheral venous catheter will be removed and the study day ended.

Drug: Oxygen (Oxymask®)

As in arm 1. Half an hour after vaccination is administered, oxygen treatment will be initiated at 6 L/min via Oxymask® and continued for 6 hours. During oxygen treatment peripheral oxygen saturation will be measured by pulsoximetry.

Venous blood samples will be collected at 3, 6 and 8 hours after baseline. After the 8-hour blood sampling, the peripheral venous catheter will be removed and the study day ended.


Drug: Atorvastatin
As in arm 1. Half an hour after vaccination is administered, oxygen treatment will be initiated at 6 L/min via Oxymask® and continued for 6 hours. During oxygen treatment peripheral oxygen saturation will be measured by pulsoximetry. A single dose of Atorvastatin 80 mg will be given immediately prior to start of oxygen. Venous blood samples will be collected at 3, 6 and 8 hours after baseline. After the 8-hour blood sampling, the peripheral venous catheter will be removed and the study day ended.
Other Name: Lipitor




Primary Outcome Measures :
  1. Plasma concentration levels over time of biomarkers of oxidative stress, apoptosis, inflammation and platelet aggregation [ Time Frame: Within 8hours from baseline ]
    Venous blood samples will be collected at 3, 6 and 8 hours after baseline and plasmaconcentration analyzed for Interleukin (IL)-6 [pg/mL], CRP [mg/L], Isoprostane [pg/mL], Soluble TNF receptor 1 [pg/mL], Soluble TNF receptor 2 [pg/mL], Soluble Fas [pg/mL], Soluble Fas ligand (pg/mL], MMP-2 [ng/mL], TIMP-2 [ng/mL], Soluble P-selectin [ng/mL], Platelet factor (PF)-4 [ng/mL], Beta-thromboglobulin [ng/mL].



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18-40 years
  • Male gender

Exclusion Criteria:

  • Female gender
  • Not willing to participate
  • Not able to communicate or to understand study instructions
  • Participation in another on-going trial
  • Any chronic disease
  • Any acute disease within 30 days of study inclusion
  • Any regular or temporary medication within 15 days of study inclusion
  • Current smokers

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02286544


Locations
Layout table for location information
Sweden
Linköping University Hospital
Linköping, Sweden, 58191
Sponsors and Collaborators
Karolinska Institutet
University Hospital, Linkoeping
Investigators
Layout table for investigator information
Principal Investigator: Lennart Nilsson, MD, PHD Department of Medical and Health Sciences, Linköping University, and Department of Cardiology, University Hospital, 58185 Linköping, Sweden

Publications:
Layout table for additonal information
Responsible Party: Leif Svensson, MD, PHD, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT02286544     History of Changes
Other Study ID Numbers: DNR-2014/252-31
2014-002282-30 ( EudraCT Number )
First Posted: November 10, 2014    Key Record Dates
Last Update Posted: December 11, 2017
Last Verified: December 2017

Keywords provided by Leif Svensson, Karolinska Institutet:
Myocardial Infarction
Oxygen
Inflammation
Acute coronary syndrome (ACS)
ST-segment elevation myocardial infarction (STEMI)
Reperfusion injury (IR-injury)
Biomarkers
Normoxemia
Salmonella typhi
Vaccine-induced inflammation
Soluble markers of apoptosis
Leukocyte subset distribution
Matrix metalloproteinase (MMP)
Biological Markers

Additional relevant MeSH terms:
Layout table for MeSH terms
Wounds and Injuries
Inflammation
Infarction
Myocardial Infarction
Ischemia
Acute Coronary Syndrome
Reperfusion Injury
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Postoperative Complications
Vaccines
Atorvastatin
Immunologic Factors
Physiological Effects of Drugs
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors