IRB-HSR# 14145 R,S Methadone: Analgesia and Pharmacokinetics in Adolescents Undergoing Scoliosis Correction

Scoliosis Clinical Trial

Official title:

IRB-HSR# 14145 R,S Methadone: Analgesia and Pharmacokinetics in Adolescents Undergoing Scoliosis Correction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01205256
• Other study ID #: 14145
• Status: Completed
• Phase: Phase 3
• First received: September 16, 2010
• Last updated: March 1, 2016
• Start date: March 2009
• Est. completion date: April 2010

Study information

• Verified date: March 2016
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This is a pilot study to determine the pharmacokinetics of (R,S) methadone in adolescents. A total of approximately 15 patients will be required. The purpose is to determine the levels of R, S methadone at various time intervals after drug administration. Patients will receive methadone 0.25 mg/kg IV at induction and a standardized anesthetic of remifentanil and propofol. At the conclusion of surgery (45 minutes prior to the completion), the patients will receive a loading dose of morphine based on respiratory rate. A morphine PCA will be utilized for postoperative analgesia. Pharmacokinetic data will be collected in addition to VAS scores, patient and parental satisfaction with analgesia, and a functional pain assessment.

Description:

Study Procedures Following Surgery:

• VAS scores will be recorded at intervals of 1,2,3,4,5,6,8,12,16,20,24, 36, 48 , 72 hrs (after extubation).

• Blood samples for PK will require 5ml per sample and may be obtained from an existing IV or direct phlebotomy and will be obtained at 0min, 5min, 10 min, 15min, 20 min, 40 min, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10 hrs, 12hrs, 24hrs, 48 hrs, 72hrs, and 96hrs after study drug administration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 19 Years

Eligibility

Inclusion Criteria:

• Pediatric scoliosis surgery secondary idiopathic scoliosis, congenital scoliosis,

• Age 12 - 19 inclusive

• ASA class I-II.

Exclusion Criteria:

• Preoperative opioid therapy in previous 2 weeks

• Known hepatic or renal impairment

• Inability to assess pain score due to neurological impairment, hearing impairment

• Allergy to methadone, morphine, fentanyl, propofol or remifentanil

• Pregnant or nursing

• Taking SSRI's, MAOI,anticonvulsants, gabapentin or lyrica

• ASA III or greater patients are excluded

• pre-existing chronic pain

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Health Services Research

Related Conditions & MeSH terms

• Scoliosis

Intervention

Drug:
• methadone
0.25mg/kg IV of racemic methadone at the induction of anesthesia.

Locations

Country	Name	City	State
United States	University of Virginia Health System	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
University of Virginia

Country where clinical trial is conducted

United States, 

References & Publications (10)

Berde CB, Beyer JE, Bournaki MC, Levin CR, Sethna NF. Comparison of morphine and methadone for prevention of postoperative pain in 3- to 7-year-old children. J Pediatr. 1991 Jul;119(1 Pt 1):136-41. — View Citation

Claar RL, Walker LS. Functional assessment of pediatric pain patients: psychometric properties of the functional disability inventory. Pain. 2006 Mar;121(1-2):77-84. Epub 2006 Feb 9. — View Citation

Dale O, Hoffer C, Sheffels P, Kharasch ED. Disposition of nasal, intravenous, and oral methadone in healthy volunteers. Clin Pharmacol Ther. 2002 Nov;72(5):536-45. — View Citation

Davis AM, Inturrisi CE. d-Methadone blocks morphine tolerance and N-methyl-D-aspartate-induced hyperalgesia. J Pharmacol Exp Ther. 1999 May;289(2):1048-53. — View Citation

Gourlay GK, Willis RJ, Wilson PR. Postoperative pain control with methadone: influence of supplementary methadone doses and blood concentration--response relationships. Anesthesiology. 1984 Jul;61(1):19-26. — View Citation

Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology. 1982 Dec;57(6):458-67. — View Citation

Holtman JR Jr, Wala EP. Characterization of the antinociceptive and pronociceptive effects of methadone in rats. Anesthesiology. 2007 Mar;106(3):563-71. — View Citation

Shir Y, Shenkman Z, Shavelson V, Davidson EM, Rosen G. Oral methadone for the treatment of severe pain in hospitalized children: a report of five cases. Clin J Pain. 1998 Dec;14(4):350-3. — View Citation

Vinik HR, Kissin I. Rapid development of tolerance to analgesia during remifentanil infusion in humans. Anesth Analg. 1998 Jun;86(6):1307-11. — View Citation

Walker LS, Greene JW. The functional disability inventory: measuring a neglected dimension of child health status. J Pediatr Psychol. 1991 Feb;16(1):39-58. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	methadone levels	Tmax (time to maximum methadone concentration) Cmax (maximum concentration) T1/2 (half-life) AUC last (area under the curve from time 0 to last sample point) AUC inf (area under the curve from time 0 to infinity) VZ (Volume of distribution in the terminal phase) CL (clearance)	0min, 5min, 10 min, 15min, 20 min, 40 min, 1, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10 hrs, 12hrs, 24hrs, 48 hrs, 72hrs, and 96hrs.	No