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Low Dose Ketamine Study on Opioid Tolerance and Hyperalgesia (KPSF)

This study is currently recruiting participants.
Verified March 2012 by Children's Research Institute
Sponsor:
Information provided by (Responsible Party):
Julia Finkel, Children's Research Institute
ClinicalTrials.gov Identifier:
NCT01325493
First received: February 25, 2011
Last updated: March 15, 2012
Last verified: March 2012
History of Changes
  Purpose

The purpose of this study is to:

  1. Establish whether ketamine can decrease opioid consumption and modulate the onset of opioid tolerance and prevent opioid-induced hyperalgesia in pediatric subjects, ages 10 years to 18 years, undergoing posterior spinal fusion and instrumentation.
  2. Develop a methodology to objectively measure the onset of opioid tolerance and opioid-induced hyperalgesia. A pupillometer will be used to obtain static and dynamic measures of pupil diameter. In order to validate pupillometry as a non-invasive measure of opioid-induced tolerance and hyperalgesia, the investigators will perform pharmacokinetic/pharmacodynamic (PK/PD) modeling using morphine and its morphine-6-glucuronide (M6G) metabolite serum concentrations and establish dose-response curves, correlating serum concentrations with pupillometry results (a rightward shift in the dose response curve indicating tolerance and a downward shift indicating hyperalgesia). Development of such a technique would allow us to detect and manage opioid tolerance and hyperalgesia in other patient populations requiring large doses of opioids.

Condition Intervention Phase
Idiopathic Scoliosis
Spondylolisthesis
 Drug: Ketamine
Drug: Normal Saline
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Health Services Research
Official Title: Modulation of μ Opioid Receptor Mediated Analgesia, Tolerance and Hyperalgesia in Children and Adolescents

Resource links provided by NLM:

MedlinePlus related topics: Scoliosis
U.S. FDA Resources

Further study details as provided by Children's Research Institute:

Primary Outcome Measures:
  • Total opioid use [ Time Frame: up to 5 days ] [ Designated as safety issue: No ]
    Establish whether ketamine can decrease opioid consumption and modulate the onset of opioid tolerance and prevent opioid-induced hyperalgesia in pediatric subjects, ages 10 years to 18 years, undergoing posterior spinal fusion and instrumentation.


Secondary Outcome Measures:
  • Pupillometry [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    Baseline pupillometry will be done in the surgical preparation area using the Optometrics infrared pupillometer. Static pupillometry consists of measurement of the initial pupil diameter. Amplitude of constriction, velocity of constriction, velocity of redilatation, latency and duration of reaction are measured as dynamic pupillometric parameters.


Estimated Enrollment: 50
Study Start Date: January 2010
Estimated Study Completion Date: May 2012
Estimated Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Normal Saline
Normal Saline given 0.5mg/kg intravenous (IV) load followed by an intraoperative continuous infusion at 0.25mg/kg/h and a postoperative infusion at 0.1mg/kg/h
 Drug: Normal Saline
Normal saline given 0.5mg/kg intravenous (IV) load followed by an intraoperative continuous infusion at 0.25mg/kg/h and a postoperative infusion at 0.1mg/kg/h
Other Name: 0.90% NaCl
Active Comparator: Ketamine
ketamine 0.5mg/kg intravenous (IV) load followed by an intraoperative continuous infusion at 0.25mg/kg/h and a postoperative infusion at 0.1mg/kg/h
 Drug: Ketamine
ketamine 0.5mg/kg intravenous (IV) load followed by an intraoperative continuous infusion at 0.25mg/kg/h and a postoperative infusion at 0.1mg/kg/h
Other Name: Ketanest, Ketaset, and Ketalar

  Eligibility

Ages Eligible for Study:   10 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The subject is 10 to 18 years of age
  2. The subject's American Society of Anesthesiologists physical status is ASA 1, 2 or 3 (see appendix I)
  3. The subject is scheduled for elective posterior spinal fusion and instrumentation.
  4. The subject's parent/legally authorized guardian has given written informed consent to participate

Exclusion Criteria:

  1. The subject has a history or a family (parent or sibling) history of malignant hyperthermia
  2. The subject is pregnant or nursing.
  3. The subject has known significant renal disorders determined by medical history, physical examination or laboratory tests
  4. The subject has a known or suspected allergy to morphine, remifentanil or ketamine
  5. The subject is an ASA classification of 4 or greater (See Appendix I)
  6. The subject is scheduled for a surgical sub-procedure (i.e. anterior spinal fusion)
  7. The subject is unable to self-administer morphine using patient-controlled analgesia (PCA) pump
  8. The subject had a recent opioid exposure (within 1 month of surgery)
  9. The subject is obese (body mass index >30kg/m2)
  10. The subject is planned for elective postoperative ventilation
  11. The subject has a known ocular disease not permitting pupillometric examination
  12. The subject has used any investigation products in the past 30 days
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01325493

Contacts
Contact: Sophie Pestieau, MD 202-476-2025 ext 2025 spestiea@cnmc.org
Contact: Julie C Finkel, MD 202-476-4867 ext 4867 jfinkel@cnmc.org

Locations
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Sophie Pestieau, MD     202-476-4914 ext 4914     spestiea@cnmc.org    
Contact: Julie C Finkel, MD     202-476-4867 ext 4867     jfinkel@cnmc.org    
Sponsors and Collaborators
Children's Research Institute
Investigators
Principal Investigator: Pestieau Sophie, MD Children's Research Institute
Study Director: Finkel C Julie, MD Children's Research Institute
  More Information

No publications provided

Responsible Party: Julia Finkel, Director of Research, Children's Research Institute
ClinicalTrials.gov Identifier: NCT01325493     History of Changes
Other Study ID Numbers: 4735
Study First Received: February 25, 2011
Last Updated: March 15, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Research Institute:
opioid tolerance
hyperalgesia
scoliosis
pupillometry

Additional relevant MeSH terms:
Spondylolisthesis
Hyperalgesia
Scoliosis
Somatosensory Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Curvatures
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Spondylolysis
Spondylosis
Ketamine
 Analgesics, Opioid
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics

ClinicalTrials.gov processed this record on May 16, 2013