ScoliosisPhase 1NCT01677650

Pharmacogenomics of Methadone in Spine Fusion Surgery

A Phase 1 study testing Methadone in people with Scoliosis and Kyphosis, run by Northwestern University at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Scoliosis, Kyphosis
What is being tested?: Methadone
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: 1 siteUnited States
Study dates: Mar 2014to Jan 2015
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

ASA physical status I, II, and III
male and non-pregnant female
English-speaking
undergoing elective < 3 vertebral level lumbar spine fusion (with and without interbody fusion)

Who cannot join

Use of more than the equivalent of 20 mg of IV morphine/24 hr in the past 2 weeks
history of substance abuse at any time in the past
known QT prolongation
Non-elective operations (i.e., cancer or trauma)
severe hepatic impairment (serum albumin <3.0 g/dL, history of liver disease)
pregnancy

Trial locations and contacts

1 site in 1 country.

United States1 site

Northwestern Memorial Hospital
Chicago, Illinois, 60611

Other trials in United States

About this study

Official title: The Influence of Pharmacogenetics on Methadone Dose, Safety, and Outcomes After Spine Fusion

The overall objective is to develop a patient oriented research program to efficiently evaluate the effects of pharmacogenetic variants on the dose-response relationships and safety of opioids and non-opioid analgesics. If an opioid regimen can be created that produces excellent opioid analgesia with minimal toxicity related to supratherapeutic opioid concentrations (i.e., ventilatory depression), other non-opioid analgesics (i.e., gabapentin/pregabalin, ketamine, lidocaine, cyclooxygenase inhibitors, etc.) that may decrease preoperative opioid requirements can be more efficiently and safely evaluated. These interventions may limit the opioid related toxicities related to effect site concentrations that are below those required when opioids are the predominant analgesic, such as opioid related ileus. Methadone's slow elimination clearance and limited pharmacokinetic drug-drug interactions make it an attractive perioperative opioid. The first step towards personalized opioid analgesia is to determine the effect of common pharmacogenetic variants that affect either methadone metabolism (CYP2B6) or opioid elimination.

Read the detailed description

This study is being done to find the optimal dose of methadone (a long acting pain medication) that decreases the amount of pain that people have after spine surgery. Five different doses of methadone will be compared to each other, while keeping the remainder of the anesthetic routine for surgery. The investigators will determine the analgesic dose-response of methadone. The investigators will also determine the effect of methadone on the incidence of opioid related side effects, the quality of outcome of recovery, and the change in the 3-month opioid use.

Conditions: Scoliosis, Kyphosis
Being tested: Methadone
Keywords: Spinal Fusion, Opioid Analgesia
Medical subject headings: Scoliosis, Kyphosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MethadoneDrug
Also called Dolophine
Methadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg

Study groups in NCT01677650
Study group	Role	What they receive
Methadone 0.5 mg/kg	Active comparator	Methadone 0.5 mg/kg Receives: Drug: Methadone
Methadone 0.4 mg/kg	Experimental	Methadone 0.4 mg/kg Receives: Drug: Methadone
Methadone 0.3 mg/kg	Active comparator	Methadone 0.3 mg/kg Receives: Drug: Methadone
Methadone 0.2 mg/kg	Active comparator	Methadone 0.2 mg/kg Receives: Drug: Methadone
Methadone 0.15 mg/kg	Active comparator	Methadone 0.15 mg/kg Receives: Drug: Methadone

What is being measured

The primary outcome is the main question the study is designed to answer.

Time until initial request for postoperative analgesic.
Measured: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration

Secondary outcomes (13)

The determination of minimum effective analgesic concentration of methadone.
Measured: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Postoperative pain at rest and with movement (numerical rating scale, NRS)
Measured: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
The number of occurrences of ventilatory depression during each evaluation interval
Measured: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Nausea and vomiting: number of rescue antiemetic doses and episodes of emesis
Measured: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Level of sedation (modified Observer's Assessment of Alertness and Sedation Scale, modified OAA/S scale)
Measured: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Occurence of pruritis
Measured: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Algometry to assess pain tolerance
Measured: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Degree of bother associated with opioid-related adverse effects: Opioid-related Symptom Distress Scale (OR-SDS)
Measured: 24, 48, and 72 hours after methadone administration
Quality of Recovery: Quality of Recovery-40 score
Measured: 24, 48, and 72 hours after methadone administration
Patient analgesic satisfaction
Measured: 24, 48, and 72 hours after methadone administration
Assessment of back condition pre and post-operatively
Measured: Pre-operatively, 6 weeks and 3 months post-operatively
Effects of common opioid related metabolic pathway polymorphisms on methadone's dose response relationships for analgesia and side effects
CYP2B6 Polymorphism effect on
1. Time to first request for analgesia
2. Secondary outcomes
Measured: Preoperatively
Pupillometry for assessment of sedation
Measured: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2014Jan 2015

First posted3 Sep 2012 (estimated)
Study startMar 2014
Primary completionJan 2015 (estimated)
Study completionJan 2015 (estimated)

Why it stopped: Investigator moved to new institution

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (23)Papers the sponsor has linked to this study.
Other trials for ScoliosisStudies of the same condition, open and under way.
More trials run by Northwestern UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01677650
Sponsor's protocol ID: STU00064915
Status last verified: Apr 2015
First submitted: 30 Aug 2012
Last updated: 22 Apr 2015
Results posted: No
Data monitoring committee: No

Publications

Rajaee SS, Bae HW, Kanim LE, Delamarter RB. Spinal fusion in the United States: analysis of trends from 1998 to 2008. Spine (Phila Pa 1976). 2012 Jan 1;37(1):67-76. doi: 10.1097/BRS.0b013e31820cccfb.
PubMed 21311399
Jadad AR, Browman GP. The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA. 1995 Dec 20;274(23):1870-3.
PubMed 7500538
Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24.
PubMed 20418538
Upton RN, Semple TJ, Macintyre PE. Pharmacokinetic optimisation of opioid treatment in acute pain therapy. Clin Pharmacokinet. 1997 Sep;33(3):225-44. doi: 10.2165/00003088-199733030-00005.
PubMed 9314613
Taylor S, Kirton OC, Staff I, Kozol RA. Postoperative day one: a high risk period for respiratory events. Am J Surg. 2005 Nov;190(5):752-6. doi: 10.1016/j.amjsurg.2005.07.015.
PubMed 16226953
Taylor S, Voytovich AE, Kozol RA. Has the pendulum swung too far in postoperative pain control? Am J Surg. 2003 Nov;186(5):472-5. doi: 10.1016/j.amjsurg.2003.07.021.
PubMed 14599609
Liu N, Kuhlman G, Dalibon N, Moutafis M, Levron JC, Fischler M. A randomized, double-blinded comparison of intrathecal morphine, sufentanil and their combination versus IV morphine patient-controlled analgesia for postthoracotomy pain. Anesth Analg. 2001 Jan;92(1):31-6. doi: 10.1097/00000539-200101000-00007.
PubMed 11133596
Joris J, Kaba A, Lamy M. Transition between anesthesia and post-operative analgesia: relevance of intra-operative administration of analgesics. Acta Anaesthesiol Belg. 2001;52(3):271-9.
PubMed 11732383
Carroll IR, Angst MS, Clark JD. Management of perioperative pain in patients chronically consuming opioids. Reg Anesth Pain Med. 2004 Nov-Dec;29(6):576-91. doi: 10.1016/j.rapm.2004.06.009.
PubMed 15635517
Yaksh TL, Hua XY, Kalcheva I, Nozaki-Taguchi N, Marsala M. The spinal biology in humans and animals of pain states generated by persistent small afferent input. Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7680-6. doi: 10.1073/pnas.96.14.7680.
PubMed 10393880
Parker RK, Holtmann B, White PF. Effects of a nighttime opioid infusion with PCA therapy on patient comfort and analgesic requirements after abdominal hysterectomy. Anesthesiology. 1992 Mar;76(3):362-7. doi: 10.1097/00000542-199203000-00007.
PubMed 1539846
Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology. 1982 Dec;57(6):458-67. doi: 10.1097/00000542-198212000-00005. No abstract available.
PubMed 6128949
Chui PT, Gin T. A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine. Anaesth Intensive Care. 1992 Feb;20(1):46-51. doi: 10.1177/0310057X9202000109.
PubMed 1609941
van Dorp EL, Kest B, Kowalczyk WJ, Morariu AM, Waxman AR, Arout CA, Dahan A, Sarton EY. Morphine-6beta-glucuronide rapidly increases pain sensitivity independently of opioid receptor activity in mice and humans. Anesthesiology. 2009 Jun;110(6):1356-63. doi: 10.1097/ALN.0b013e3181a105de.
PubMed 19461298
Egan TD, Huizinga B, Gupta SK, Jaarsma RL, Sperry RJ, Yee JB, Muir KT. Remifentanil pharmacokinetics in obese versus lean patients. Anesthesiology. 1998 Sep;89(3):562-73. doi: 10.1097/00000542-199809000-00004.
PubMed 9743391

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Scoliosis trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Influence of Pharmacogenetics on Methadone Dose, Safety, and Outcomes After Spine Fusion
ClinicalTrials.gov ID: NCT01677650
Acronym / sponsor ID: STU00064915
Conditions: Scoliosis, Kyphosis
Keywords: Spinal Fusion, Opioid Analgesia
Phase: Phase 1
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Investigator moved to new institution
Enrolment: 0 participants (actual)
Lead sponsor: Northwestern UniversityUniversity, hospital or other
Study start: Mar 2014
Primary completion: Jan 2015 (estimated)
Study completion: Jan 2015 (estimated)
First posted: 3 Sep 2012 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
Methadone 0.5 mg/kg	Active comparator	Drug: MethadoneMethadone 0.5 mg/kg
Methadone 0.4 mg/kg	Experimental	Drug: MethadoneMethadone 0.4 mg/kg
Methadone 0.3 mg/kg	Active comparator	Drug: MethadoneMethadone 0.3 mg/kg
Methadone 0.2 mg/kg	Active comparator	Drug: MethadoneMethadone 0.2 mg/kg
Methadone 0.15 mg/kg	Active comparator	Drug: MethadoneMethadone 0.15 mg/kg

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

ASA physical status I, II, and III
male and non-pregnant female
English-speaking
undergoing elective < 3 vertebral level lumbar spine fusion (with and without interbody fusion)

Key exclusion criteria (6 listed)

Use of more than the equivalent of 20 mg of IV morphine/24 hr in the past 2 weeks
history of substance abuse at any time in the past
known QT prolongation
Non-elective operations (i.e., cancer or trauma)
severe hepatic impairment (serum albumin <3.0 g/dL, history of liver disease)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MethadoneAlso: DolophineMethadone IV Pre-Induction of Anesthesia 0.15 to 0.5 mg/kg	Drug	Methadone 0.15 mg/kg, Methadone 0.2 mg/kg, Methadone 0.3 mg/kg, Methadone 0.4 mg/kg, Methadone 0.5 mg/kg

Primary outcome

Time until initial request for postoperative analgesic.
Time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration

13 secondary outcomes

The determination of minimum effective analgesic concentration of methadone.
Time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Postoperative pain at rest and with movement (numerical rating scale, NRS)
Time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
The number of occurrences of ventilatory depression during each evaluation interval
Time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Nausea and vomiting: number of rescue antiemetic doses and episodes of emesis
Time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Level of sedation (modified Observer's Assessment of Alertness and Sedation Scale, modified OAA/S scale)
Time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Occurence of pruritis
Time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Algometry to assess pain tolerance
Time frame: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration
Degree of bother associated with opioid-related adverse effects: Opioid-related Symptom Distress Scale (OR-SDS)
Time frame: 24, 48, and 72 hours after methadone administration
Quality of Recovery: Quality of Recovery-40 score
Time frame: 24, 48, and 72 hours after methadone administration
Patient analgesic satisfaction
Time frame: 24, 48, and 72 hours after methadone administration
Assessment of back condition pre and post-operatively
Time frame: Pre-operatively, 6 weeks and 3 months post-operatively
Effects of common opioid related metabolic pathway polymorphisms on methadone's dose response relationships for analgesia and side effects
Time frame: Preoperatively
Pupillometry for assessment of sedation
Time frame: Pre-operatively, 60 minutes after extubation, 24, 48, and 72 hours after methadone administration

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2015.
Background: PubMed 21311399Rajaee SS, Bae HW, Kanim LE, Delamarter RB. Spinal fusion in the United States: analysis of trends from 1998 to 2008. Spine (Phila Pa 1976). 2012 Jan 1;37(1):67-76. doi: 10.1097/BRS.0b013e31820cccfb.
Background: PubMed 7500538Jadad AR, Browman GP. The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA. 1995 Dec 20;274(23):1870-3.
Background: PubMed 20418538Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24.
Background: PubMed 9314613Upton RN, Semple TJ, Macintyre PE. Pharmacokinetic optimisation of opioid treatment in acute pain therapy. Clin Pharmacokinet. 1997 Sep;33(3):225-44. doi: 10.2165/00003088-199733030-00005.
Background: PubMed 16226953Taylor S, Kirton OC, Staff I, Kozol RA. Postoperative day one: a high risk period for respiratory events. Am J Surg. 2005 Nov;190(5):752-6. doi: 10.1016/j.amjsurg.2005.07.015.
Background: PubMed 14599609Taylor S, Voytovich AE, Kozol RA. Has the pendulum swung too far in postoperative pain control? Am J Surg. 2003 Nov;186(5):472-5. doi: 10.1016/j.amjsurg.2003.07.021.
Background: PubMed 11133596Liu N, Kuhlman G, Dalibon N, Moutafis M, Levron JC, Fischler M. A randomized, double-blinded comparison of intrathecal morphine, sufentanil and their combination versus IV morphine patient-controlled analgesia for postthoracotomy pain. Anesth Analg. 2001 Jan;92(1):31-6. doi: 10.1097/00000539-200101000-00007.
Background: PubMed 11732383Joris J, Kaba A, Lamy M. Transition between anesthesia and post-operative analgesia: relevance of intra-operative administration of analgesics. Acta Anaesthesiol Belg. 2001;52(3):271-9.
Background: PubMed 15635517Carroll IR, Angst MS, Clark JD. Management of perioperative pain in patients chronically consuming opioids. Reg Anesth Pain Med. 2004 Nov-Dec;29(6):576-91. doi: 10.1016/j.rapm.2004.06.009.
Background: PubMed 10393880Yaksh TL, Hua XY, Kalcheva I, Nozaki-Taguchi N, Marsala M. The spinal biology in humans and animals of pain states generated by persistent small afferent input. Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7680-6. doi: 10.1073/pnas.96.14.7680.
Background: PubMed 1539846Parker RK, Holtmann B, White PF. Effects of a nighttime opioid infusion with PCA therapy on patient comfort and analgesic requirements after abdominal hysterectomy. Anesthesiology. 1992 Mar;76(3):362-7. doi: 10.1097/00000542-199203000-00007.
Background: PubMed 6128949Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology. 1982 Dec;57(6):458-67. doi: 10.1097/00000542-198212000-00005. No abstract available.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Dhanesh K. Gupta, M.D. principal investigator

Northwestern University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Methadone in people with Scoliosis and Kyphosis, run by Northwestern University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 22 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time until initial request for postoperative analgesic. (time frame: 60 minutes after extubation, 24, 48, and 72 hours after methadone administration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01677650, which also lists 23 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2015.