Clinical trial NCT01052207: Pilot Study Assessing Oxidative Stress in Children
Official title: Prevalence of Oxidative Stress in Critically Ill Children and Its Relationship to Adrenal Insufficiency; a Pilot Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Adrenal Insufficiency
Critical Illness
Keywords: Biological Response Modifiers
Endocrinology
Hormone Dysfunction
Hormones
Neuroendocrinology
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Children's Healthcare of Atlanta
First posted: 2010-01-20
Enrollment: 102
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Population 1 consists of critically ill patients being care for in quaternary PICU.

Population 2 consists of relatively healthy children undergoing MRI for sedation

Brief summary: Role fo oxidative stress in adrenal insufficiency has not been studied. The degree of oxidative stress and it's role in pediatric critical illness is unknown. Potential for significant alterations to many of thew body's regulatory pathways may result from severe oxidative stress. Further is needed to delineate what if any role oxidative stress may play

Detailed description: Adrenal insufficiency (AI) is common in critically ill children and adults. AI is a condition in which the adrenal glands, located above the kidneys, do not make enough hormones or our body is unable to use the hormones made. A hormone is a chemical that helps control different kinds of body functions. The hormones being studied can influence blood pressure and how fast the heart beats. Doctors want to know why children need extra hormones when they are critically ill. In our pediatric intensive care unit (PICU) we treat AI with a set of standard orders. By doing this, we have shown that AI is common in many types of sickness and that blood pressure improves when extra hormones are given. We also found that people's heart and blood pressure did not always match the level of a certain hormone, called cortisol, in their blood.

Since cortisol levels alone don't always show AI, and children with normal hormone levels still benefit from steroids, doctors are looking for a better understanding of AI. Finding reasons that children develop AI may help doctors find other ways to improve AI.

One promising focus of AI is the role of oxidative stress (OS). OS is a term used to describe a group of chemical reactions that involve oxygen. Emory's adult intensive care units have shown a significant increase in OS in critically ill patients. Normally our body's cortisol acts by binding to glucocorticoid (a class of hormone) receptors (GR) within cells. Many studies have shown that OS increases steroid resistance by changing the GR structure and function. Studies involving OS and GR problems have not been done with children.

We aim to:

1. Find out how many sick children have OS in the PICU.
2. Find out the normal OS level of healthy children.
3. Decide if OS causes adrenal insufficiency.

Eligibility criteria: Inclusion Criteria:

Critically Ill subjects:

1. All patients, birth-18 years, admitted to the pediatric intensive care unit that require blood to be drawn as part of medical management consistent with "standard of care".
2. Admission to the PICU within the last 24 hours.
3. Subjects' legal guardian shall possess the ability to understand the purposes and risks of the study and provide an informed consent signature.

Healthy control subjects:

1. All healthy children, birth-18 years, who are having semi-elective magnetic resonance imaging (MRI) that require peripheral intravenous (PIV) catheters placed to provide sedation.

Exclusion Criteria:

Critically Ill subjects:

1. Have received steroids within the last 30 days.
2. Pre-existing/known neuroendocrine disorder, including but not limited to disorders of the hypothalamus, pituitary, adrenal, pancreas, or thyroid gland.
3. Have been treated at anytime with antipsychotic medication.
4. Human immunodeficiency virus (HIV) positive.
5. Patients who have received etomidate.
6. Patients weighing less than or equal to 6 kilograms.
7. Developmentally delayed.
8. Medical urgency preventing timely administration of the consenting process, or any condition that, in the opinion of the attending physician, would place the patient at undue risk by participating.
9. Other technical considerations that would prevent the timely acquisition of sufficient samples such as (but not limited to) hour of admission or absence of a study team member.
10. Parent or legal guardian (or patient when applicable) refuses to sign informed consent.

Healthy control subjects:

1. Have received steroids within the last 30 days.
2. Have a pre-existing/known neuroendocrine disorder, including but not limited to disorders of the hypothalamus, pituitary, adrenal, pancreas, or thyroid gland.
3. Have been treated at anytime with antipsychotic medication.
4. Human immunodeficiency virus (HIV) positive.
5. Patients who have received etomidate.
6. Patients weighing less than or equal to 6 kilograms.
7. Developmentally delayed.
8. Medical urgency preventing timely administration of the consenting process, or any condition that, in the opinion of the attending physician, would place the patient at undue risk by participating.
9. Other technical considerations that would prevent the timely acquisition of sufficient samples such as (but not limited to) hour of admission or absence of a study team member.
10. Parent or legal guardian (or patient when applicable) refuses to sign informed consent.

Primary outcomes:
measure: Pediatric Logistic Organ Dysfunction Score in Critically Ill Children
timeFrame: 1 years
Secondary outcomes:
measure: Establish the OS Profile of Healthy Children to Act as Controls and Help Establish the Normal Pediatric Baseline.
timeFrame: 2 years
measure: Analysis of Clinical Data to Determine Correlation of OS With AI and Evaluation of OS as a Potential Biomarker.
timeFrame: 2 years
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta at Egleston
state: Georgia
Study officials:
affiliation: Emory University & Children's Healthcare of Atlanta
name: Kiran Hebbar, MD, FCCM
role: PRINCIPAL_INVESTIGATOR
References: