Pharmacogenetic Morphine Spine Study

Pain Clinical Trial

Official title:

Personalizing Perioperative Morphine Analgesia for Adolescents Undergoing Major Spine Surgeries

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01839461
• Other study ID #: 2009-0973
• Status: Completed
• Start date: July 2009
• Est. completion date: April 2, 2019

Study information

• Verified date: April 2019
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 137
• Est. completion date: April 2, 2019
• Est. primary completion date: April 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pain

Locations

Country	Name	City	State
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

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* Note: There are 69 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Side-effect measures	Incidences of respiratory depression, sedation, postoperative nausea and vomiting (PONV) in the recovery phase will be collected.	First 48 hours post surgery
Primary	Immediate postoperative pain scores in the 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	postoperative intravenous morphine requirement	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
Secondary	Chronic pain pre-operatively	Participants will complete questionnaires regarding pain since surgery was completed	Pre-operative
Secondary	Chronic pain post-operatively	Participants will complete questionnaires regarding pain since surgery was completed	2 - 6 months post-operative
Secondary	Chronic pain post-operatively	Participants will complete questionnaires regarding pain since surgery was completed	10 - 12 months post-operative