Pharmacokinetics of Low Dose Ketamine Infusion - Full Text View

Sponsored by:	University of Texas Southwestern Medical Center
Information provided by:	University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT00618397

Purpose

Opioids, such as fentanyl, are commonly used in PICU patients to provide comfort and pain control. Opioid tolerance, the need to increase the dose of medication to achieve the same effect,is seen in PICU children who require opioid infusions. Animals and human studies have shown that activation of the N-methyl-D-aspartate (NMDA) receptor is involved in the development of opioid tolerance and that deactivation of this receptor can slow the development of tolerance. Ketamine, an NMDA receptor antagonists, turns off the NMDA receptor. Ketamine is used to provide sedation and anesthesia in children. Its use in inhibiting the development of opioid tolerance has not been tested in children. We aim to determine ketamine's effectiveness in the treatment of tolerance in PICU patients who require fentanyl infusions to treat pain and discomfort .

Some physicians have reported using ketamine doses of 0.04mg/kg/hr to 0.5mg/kg/hr to inhibit opioid tolerance. We propose to study the sedative effect, and the metabolism of, three doses of ketamine, 0.1mg/kg/hr, 0.3mg/kg/hr, and 0.5mg/kg/hr.

Patients admitted to the PICU, requiring a breathing machine and fentanyl infusion for discomfort or pain control will be enrolled. Patients' age three to eighteen years will be enrolled. Patients will receive a ketamine infusion once their COMFORT scores indicate an adequate sedation/comfort level on their current sedation regimen. The COMFORT score is a validated scale that measures distress in PICU patients. The COMFORT score will be continued for the twelve hours the patient receives the ketamine to test whether the ketamine adds to the level of sedation. Blood samples during and following the ketamine infusion will be taken to determine how ketamine and norketamine (one of ketamine's metabolites) are used in the body.

To determine the effect of ketamine on tolerance it must be a ketamine dose that does not cause additional sedation. The goal of this study is to define a non-sedating dose of ketamine and define how it is used by the body. A non-sedating ketamine dose could be added to current sedation regimens allowing us to monitor the development of tolerance without the confusion of added sedation. The data obtained in this study will be used to design a study to further investigate the effect of ketamine on opioid tolerance.

Condition	Intervention	Phase
Sedation Opioid Tolerance	Drug: Ketamine	Phase I

Drug Information available for: Ketamine hydrochloride Ketamine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Open Label, Single Group Assignment, Pharmacokinetics Study
Official Title:	Phase I Trial to Determine Steady State Pharmacokinetics and Sedative Effects of Low Dose Ketamine Infusion

Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:

To establish if continuous infusions of ketamine in doses of 0.01mg/kg/hr, 0.1mg/kg/hr and 0.5mg/kg/hr cause serum levels > 1 mcg/ml. [ Time Frame: 6 and 12 hours after begining infusion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To define the pharmacokinetics of continuous infusion ketamine in doses of 0.01mg/kg/hr, 0.1mg/kg/hr and 0.5mg/kg/hr. [ Time Frame: 6 and 12 hours after infusion ] [ Designated as safety issue: No ]

Estimated Enrollment:	15
Study Start Date:	June 2006
Estimated Study Completion Date:	December 2008
Estimated Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm 1: Experimental Ketamine will be administered in doses of 0.01mg/kg/hr, 0.1mg/kg/hr and 0.5mg/kg/hr to in PICU patients that meet eligibility criteria.	Drug: Ketamine Ketamine administered in doses of 0.01mg/kg/hr, 0.1mg/kg/hr and 0.5mg/kg/hr to PICU patients.

Show Detailed Description

Eligibility

Ages Eligible for Study:	3 Years to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients will be eligible if they meet the following criteria:
Children age one three (3) years to eighteen (18) years, requiring admission to the Pediatric ICU, who require intubation for respiratory failure and continuous infusion fentanyl.
Patients of both genders, all races and ethnic backgrounds will be eligible.
Patients will need to have AST and ALT evaluated within the two weeks prior to enrollment, with the result being within two times the normal range.

Patients who have not had AST and ALT evaluated within two weeks will have to be evaluated prior to enrollment. Serum will be evaluated for AST and ALT when convenient to other lab testing prior to enrollment.

Patients meeting the above criteria will be eligible regardless of nutritional status, performance status or recovery from prior medical treatment.
Patients will not be excluded if they require simultaneous infusions of sedation with benzodiazepine.
Enrollment will require parental consent.

Exclusion Criteria:

Patients will not be eligible if they meet any of the following criteria:
Patients who are currently on oral analgesia or sedation
Patients who have a prior history of drug or alcohol dependence/abuse.
Patients who are allergic to opioids.
Patients who are allergic to ketamine or any NMDA antagonist. Patients in whom significant elevation of blood pressure would constitute a serious hazard
Patients with documented or clinical concern for elevated intracranial pressure.
Patients with known liver dysfunction as evidenced by AST and ALT two times the normal limit within the past two weeks.
Patients who are being medically paralyzed as part of their current treatment.
Patients with any underlying neurologic condition, or impairment, which would interfere with their perception of, or response to, pain or discomfort.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00618397

Contacts

Contact: Cindy Darnell, MD

214-456-7968

cindy.darnell@childrens.com

Locations

United States, Texas
Children's Medical Center Dallas, University of Texas Southwestern	Recruiting
Dallas, Texas, United States, 75235
Contact: Cindy Darnell, MD 214-456-7968 cindy.darnell@childrens.com
Principal Investigator: Cindy Darnell, MD

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Investigators

Principal Investigator:

Cindy Darnell, MD

University of Texas Southwestern

More Information

No publications provided

Responsible Party:	University of Texas Southwestern ( Cindy Darnell, MD/ Assistant Professor Pediatrics )
Study ID Numbers:	042006035
Study First Received:	February 6, 2008
Last Updated:	February 6, 2008
ClinicalTrials.gov Identifier:	NCT00618397 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Texas Southwestern Medical Center:

ketamine
pharmcokinetics
sedation

critical care
opioid tolerance
NMDA Antagonist

Study placed in the following topic categories:

Anesthetics, Intravenous
Excitatory Amino Acids
Neurotransmitter Agents
Anesthetics, General
Ketamine

Central Nervous System Depressants
Anesthetics
Peripheral Nervous System Agents
Analgesics
Anesthetics, Dissociative

Additional relevant MeSH terms:

Anesthetics, Intravenous
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Agents
Anesthetics, Dissociative
Pharmacologic Actions

Sensory System Agents
Anesthetics, General
Therapeutic Uses
Ketamine
Peripheral Nervous System Agents
Analgesics
Central Nervous System Agents
Excitatory Amino Acid Antagonists

ClinicalTrials.gov processed this record on May 07, 2009