Clinical trial NCT02732795: Sleep Apnea and Obesity Affects on Morphine Pharmacokinetics
Official title: Effects of Obstructive Sleep Apnea Syndrome and Obesity on Morphine Pharmacokinetics in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pediatric Sleep Apnea
Obesity
Morphine Metabolism
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2016-04-11
Enrollment: 43
Sex: ALL
Minimum age (years): 5
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.)

Primary outcomes:
measure: Plasma Morphine Area Under the Curve (AUC)
timeFrame: Through study completion, up to 24 hours after study initiation
measure: Maximum Plasma Morphine Concentration (Cmax)
timeFrame: Through study completion, up to 24 hours after study initiation
measure: Time to Maximum Plasma Morphine Concentration (Tmax)
timeFrame: Through study completion, up to 24 hours after study initiation
measure: Half Life of Plasma Morphine Concentration (T1/2)
timeFrame: Through study completion, up to 24 hours after study initiation
measure: Plasma Morphine Clearance (Cl)
timeFrame: Through study completion, up to 24 hours after study initiation
measure: Plasma Morphine Volume of Distribution (Vd)
timeFrame: Through study completion, up to 24 hours after study initiation
measure: Plasma Morphine 3-glucuronide (M3G) Maximum Plasma Concentration (Cmax)
timeFrame: Through study completion, up to 24 hours after study initiation
measure: Time to Maximum Morphine 3-glucuronide (M3G) Concentration (Tmax)
timeFrame: Through study completion, up to 24 hours after study initiation
measure: Morphine 3-glucuronide (M3G) to Morphine ratio
timeFrame: Through study completion, up to 24 hours after study initiation
measure: Morphine 3-glucuronide (M3G) to Morphine 6-glucuronide (M6G) ratio
timeFrame: Through study completion, up to 24 hours after study initiation
Secondary outcomes:
measure: Biomarker concentrations
timeFrame: Through study completion, up to 24 hours after study initiation
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Bloomberg Children's Hospital
state: Maryland
Study officials:
References: