Pharmacogenetic Morphine Spine Study

October 3, 2019 updated by: Children's Hospital Medical Center, Cincinnati

Personalizing Perioperative Morphine Analgesia for Adolescents Undergoing Major Spine Surgeries

The purpose of this research study is to identify factors and genes (the DNA material that determines the makeup of the human body) that may be associated with how children cope with pain and respond to pain medication. Morphine is a pain medication commonly prescribed after this surgery during the hospital stay. The investigators want to study factors that may be associated with morphine requirement after surgery and side-effects from morphine. They will use pharmacometric models to identify dosing guidelines and factors associated with individual variability in metabolism and efficacy/safety of morphine. They will also study psychological, genetic and epigenetic factors associated with acute and chronic post-surgical pain after spine surgery. The investigators expect that the information obtained in this research study will help to develop effective, safer, and tailored treatment options in the future.

Study Overview

Status

Completed

Conditions

Detailed Description

Safe and effective analgesia is an important unmet medical need in children. Despite efforts to promote non-pharmacologic interventions, drug treatment remains the standard of care for children experiencing severe pain following surgery. Inadequate pain relief after invasive surgery, and side effects from analgesics such as morphine occur frequently in up to 50% of children. A study of patient-controlled analgesia morphine use after spine surgery in adolescents observed a 45% incidence of postoperative nausea and vomiting 15% incidence of pruritis and 7% incidence of respiratory depression. Among the drugs available, the opioids, specifically morphine is the most commonly employed. Morphine has a narrow therapeutic index, with the most fatal toxicity being respiratory depression. For morphine, like most opioids, there is a fine balance in dosing regimen between optimal pain control and safety in terms of decreasing morphine's respiratory depressant/ sedative side effects. Inadequate pain relief and analgesic side effects have major clinical, behavioral and economic consequences. Neither evidence-based dosing guidelines nor rigorous documentation of therapeutic benefit for morphine has been ascertained in the pediatric patient population. Despite aggressive pain management after spine surgery, findings showed that neither children's pain nor their analgesic use diminished significantly over time. As such, there is a critical knowledge gap in the medical literature that significantly impacts the pediatric pain management. In recognition of this therapeutic challenge the investigators plan to evaluate the determinants of inter-individual differences in opioid analgesic responsiveness and adverse effects in children. Adolescents following spine surgery have a great variability in morphine requirements with greater use as they became older. Analgesic dosing is dependent on appreciation of the interplay between pharmacokinetics, pharmacodynamics and therapeutics. These factors are often poorly understood, where the effective control of procedural pain for example, remains problematic. Suitable pharmacological alternatives to opioid treatment for moderate to severe pain in children after surgery are limited and consequently there is a need for a critical evaluation of the existing opioids and research reports.

Recently a number of small studies have shown the association of single nucleotide polymorphism in genes in the pain pathway, with altered pain response to a stimulus or altered response to opioids following a painful procedure. Age, gender, cultural influences, anxiety, type of surgical procedure and genetic factors can all influence the response. By extending follow up of patients to years after surgery, the aims were amended to include evaluation of chronic post-surgical outcomes.

We will be collecting data on pain scores, opioid effects, psychological questionnaires, blood samples and pupillometry data.

Study Type

Observational

Enrollment (Actual)

137

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Childrens Hospital Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Children ages 10 to 18, inclusive, years scheduled for spinal surgical procedures.

Description

Inclusion Criteria:

  • Children aged 10 to 18, inclusive, years of age
  • Diagnosis of Idiopathic scoliosis, kyphosis and/or kyphoscoliosis
  • Scheduled for spine fusion

Exclusion Criteria:

  • Known hypersensitivity to morphine
  • Patients on chronic pain medication.
  • Pregnant or breastfeeding females.
  • Children with a history of or active renal or liver disease.
  • Concomitant use of medication known to induce or inhibit CYP2D6 activity including paroxetine, fluoxetine, cimetidine, duloxetine or methadone.
  • Non-English speaking patients.
  • Developmental delay.
  • Children who have problems with pupil or pupillary reaction due to disease (such as amyloidosis, bilateral Horner's syndrome, familial dysautonomia, other major neurological disorders) or preoperative medications influencing pupillary size (anti-cholinergic, narcotic medications such as codeine in cough syrup) will be recruited but pupillometry will be deferred.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immediate postoperative pain scores in the recovery room
Time Frame: 1 day ( Recovery room)
Pain score will be measured using standard and validated scales, Numeric rating scale (NRS 0 - 10). This scale has been widely validated and discriminates mild, moderate and severe pain
1 day ( Recovery room)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
postoperative intravenous morphine requirement
Time Frame: First 48 hours after surgery
Pain score will be measured using standard and validated scales, Numeric rating scale (NRS 0 - 10). This scale has been widely validated and discriminates mild, moderate and severe pain.
First 48 hours after surgery
Chronic pain pre-operatively
Time Frame: Pre-operative
Participants will complete questionnaires regarding pain since surgery was completed
Pre-operative
Chronic pain post-operatively
Time Frame: 2 - 6 months post-operative
Participants will complete questionnaires regarding pain since surgery was completed
2 - 6 months post-operative
Chronic pain post-operatively
Time Frame: 10 - 12 months post-operative
Participants will complete questionnaires regarding pain since surgery was completed
10 - 12 months post-operative

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Side-effect measures
Time Frame: First 48 hours post surgery
Incidences of respiratory depression, sedation, postoperative nausea and vomiting (PONV) in the recovery phase will be collected.
First 48 hours post surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Medical Center, Cincinnati

Investigators

  • Principal Investigator: Vidya Chidambaran, MD, Cincinnati Childrens Hospital Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Actual)

April 2, 2019

Study Completion (Actual)

April 2, 2019

Study Registration Dates

First Submitted

April 22, 2013

First Submitted That Met QC Criteria

April 23, 2013

First Posted (Estimate)

April 24, 2013

Study Record Updates

Last Update Posted (Actual)

October 7, 2019

Last Update Submitted That Met QC Criteria

October 3, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 2009-0973

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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