Sleep Apnea and Obesity Affects on Morphine Pharmacokinetics

Obesity Clinical Trial

Official title:

Effects of Obstructive Sleep Apnea Syndrome and Obesity on Morphine Pharmacokinetics in Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02732795
• Other study ID #: IRB00034512
• Status: Completed
• Phase: N/A
• Start date: July 2015
• Est. completion date: September 7, 2018

Study information

• Verified date: September 2019
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Adenotonsillectomy (AT) is one of the most common pediatric surgeries performed, and is estimated to comprise 530,000 procedures in children under 15 years of age. Historically, the leading cause for these procedures was recurrent infections; however, more recently surgical indications include sleep disordered breathing and obstructive sleep apnea (OSAS). Pre-operative polysomnography (PSG) is recommended for all children with suspected OSAS prior to undergoing AT, although it is unclear whether sleep disordered breathing characteristics predict post-operative outcomes or complications.

Obesity has become an epidemic in the pediatric population. More recently, an increased population of obese children are presenting for AT with upper airway obstruction with or without tonsillar hypertrophy, which is similar to the adult etiology of OSAS. Obesity is a multisystem disease, causing fatty liver and cardiac disease, defects in glucose metabolism, insulin resistance, leptin resistance, and creates a state of chronic inflammation. Markers for inflammation, including tumor necrosis factor (TNF)-α, C-reactive protein (CRP), leptin, interleukin (IL)-6 and IL-10, are abnormal in obese patients and have also been linked to more severe OSAS disease in children even after controlling for BMI.

In pediatrics, medication dosing is based on an actual body-weight calculation, however, recent reports suggest that this dosing method is over-dosing patients with obesity. Therefore, increased respiratory complications after surgery may be related to inappropriate intra-operative opioid dosing.

Specific Aim 1 (SA1): To compare morphine pharmacokinetics in normal children <=12 years of age, non-obese children with severe OSAS, and obese children with severe OSAS. The investigators hypothesize that obesity independently enhances morphine pharmacokinetics.

Specific Aim 2 (SA2): To determine whether biomarkers related to obesity, chronic inflammation, and OSAS predict changes to morphine pharmacokinetics. The investigators hypothesize that inflammatory and obesity-related biomarkers are elevated in overweight children with OSAS, more so in obese children with OSA, compared to lean children with OSAS. In addition, the investigators hypothesizes that leptin independently is linked to altered morphine pharmacokinetics.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: September 7, 2018
• Est. primary completion date: September 7, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years to 12 Years

Eligibility

Inclusion Criteria:

• Child presenting for surgery that will require opioids

• Age between 5 -12 years of age

OSAS group:

• Pre-operative polysomnography study conducted prior to day of surgery

Obese:

• Body weight >95th percentile for age.

Exclusion Criteria:

• Emergency procedures involving AT, including tonsillar bleeding

• Patients allergic to morphine

• Patients with comorbidities altering opioid metabolism (i.e. liver disease)

• Patients with chronic inflammatory, rheumatologic, or other confounding co-morbid diseases (i.e. Crohns disease, ulcerative colitis, sickle cell, Sjogren's, etc.)

Related Conditions & MeSH terms

• Apnea
• Morphine Metabolism
• Obesity
• Pediatric Sleep Apnea
• Sleep Apnea Syndromes

Intervention

Other:
• Morphine pharmacokinetic evaluation
Each group received morphine and blood drawn to evaluate morphine PK

Locations

Country	Name	City	State
United States	Bloomberg Children's Hospital	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma Morphine Area Under the Curve (AUC)	To determine changes in morphine AUC due to obesity and OSAS	Through study completion, up to 24 hours after study initiation
Primary	Maximum Plasma Morphine Concentration (Cmax)	To determine changes in morphine Cmax due to obesity and OSAS	Through study completion, up to 24 hours after study initiation
Primary	Time to Maximum Plasma Morphine Concentration (Tmax)	To determine changes in morphine Tmax due to obesity and OSAS	Through study completion, up to 24 hours after study initiation
Primary	Half Life of Plasma Morphine Concentration (T1/2)	To determine changes in morphine T1/2 due to obesity and OSAS	Through study completion, up to 24 hours after study initiation
Primary	Plasma Morphine Clearance (Cl)	To determine changes in morphine Cl due to obesity and OSAS	Through study completion, up to 24 hours after study initiation
Primary	Plasma Morphine Volume of Distribution (Vd)	To determine changes in morphine Vd due to obesity and OSAS	Through study completion, up to 24 hours after study initiation
Primary	Plasma Morphine 3-glucuronide (M3G) Maximum Plasma Concentration (Cmax)	To determine changes in M3G Cmax due to obesity and OSAS	Through study completion, up to 24 hours after study initiation
Primary	Time to Maximum Morphine 3-glucuronide (M3G) Concentration (Tmax)	To determine changes in M3G Tmax due to obesity and OSAS	Through study completion, up to 24 hours after study initiation
Primary	Morphine 3-glucuronide (M3G) to Morphine ratio	To determine changes in metabolism of morphine due to obesity and OSAS	Through study completion, up to 24 hours after study initiation
Primary	Morphine 3-glucuronide (M3G) to Morphine 6-glucuronide (M6G) ratio	To determine changes in metabolism of morphine due to obesity and OSAS	Through study completion, up to 24 hours after study initiation
Secondary	Biomarker concentrations	To determine whether inflammatory biomarkers correlate to the severity of sleep apnea. Biomarkers that will be studied include IL 1,6,10, CRP, TNF-alpha, leptin, and insulin.	Through study completion, up to 24 hours after study initiation