Pediatric Sleep ApneaNCT02732795
Sleep Apnea and Obesity Affects on Morphine Pharmacokinetics
A study testing Morphine pharmacokinetic evaluation in people with Pediatric Sleep Apnea and Obesity, run by Johns Hopkins University at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 5 to 12 yearsHealthy volunteers can take part
- Conditions the study is for
- Pediatric Sleep Apnea, Obesity, Morphine Metabolism
- What is being tested?
- Morphine pharmacokinetic evaluation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2015to 7 Sep 2018
- Phase
- Interventional
- 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 5 to 12 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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.
Who cannot join
- 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.)
Trial locations and contacts
1 site in 1 country.
United States1 site
Bloomberg Children's Hospital
Baltimore, Maryland, 21287
About this study
Official title: Effects of Obstructive Sleep Apnea Syndrome and Obesity on Morphine Pharmacokinetics in Children
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.
Read more
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.
- Conditions
- Pediatric Sleep Apnea, Obesity, Morphine Metabolism
- Being tested
- Morphine pharmacokinetic evaluation
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Morphine pharmacokinetic evaluationOther
Each group received morphine and blood drawn to evaluate morphine PK
| Study group | Role | What they receive |
|---|---|---|
| Morphine dosing | Experimental | Evaluating morphine pharmacokinetics (PK) in 3 groups: normal controls, children with severe OSAS, and obese children with OSAS. Morphine is dosed on ideal body weight in obese children, as recommended by manufacturer. Biomarkers were taken from patients to evaluate their relation to changes in morphine PK. Receives: Other: Morphine pharmacokinetic evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Morphine Area Under the Curve (AUC)
To determine changes in morphine AUC due to obesity and OSAS
Measured: Through study completion, up to 24 hours after study initiation
Maximum Plasma Morphine Concentration (Cmax)
To determine changes in morphine Cmax due to obesity and OSAS
Measured: Through study completion, up to 24 hours after study initiation
Time to Maximum Plasma Morphine Concentration (Tmax)
To determine changes in morphine Tmax due to obesity and OSAS
Measured: Through study completion, up to 24 hours after study initiation
Half Life of Plasma Morphine Concentration (T1/2)
To determine changes in morphine T1/2 due to obesity and OSAS
Measured: Through study completion, up to 24 hours after study initiation
Plasma Morphine Clearance (Cl)
To determine changes in morphine Cl due to obesity and OSAS
Measured: Through study completion, up to 24 hours after study initiation
Plasma Morphine Volume of Distribution (Vd)
To determine changes in morphine Vd due to obesity and OSAS
Measured: Through study completion, up to 24 hours after study initiation
Plasma Morphine 3-glucuronide (M3G) Maximum Plasma Concentration (Cmax)
To determine changes in M3G Cmax due to obesity and OSAS
Measured: Through study completion, up to 24 hours after study initiation
Time to Maximum Morphine 3-glucuronide (M3G) Concentration (Tmax)
To determine changes in M3G Tmax due to obesity and OSAS
Measured: Through study completion, up to 24 hours after study initiation
Morphine 3-glucuronide (M3G) to Morphine ratio
To determine changes in metabolism of morphine due to obesity and OSAS
Measured: Through study completion, up to 24 hours after study initiation
Morphine 3-glucuronide (M3G) to Morphine 6-glucuronide (M6G) ratio
To determine changes in metabolism of morphine due to obesity and OSAS
Measured: Through study completion, up to 24 hours after study initiation
Secondary outcomes (1)
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.
Measured: Through study completion, up to 24 hours after study initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2016 (estimated)
- Study startJul 2015
- Primary completion7 Sep 2018
- Study completion7 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pediatric Sleep ApneaStudies of the same condition, open and under way.
- More trials run by Johns Hopkins 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02732795
- Sponsor's protocol ID
- IRB00034512
- Status last verified
- Sep 2019
- First submitted
- 4 Feb 2016
- Last updated
- 9 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Obstructive Sleep Apnea Syndrome and Obesity on Morphine Pharmacokinetics in Children
- ClinicalTrials.gov ID
- NCT02732795
- Acronym / sponsor ID
- IRB00034512
- Conditions
- Pediatric Sleep Apnea, Obesity, Morphine Metabolism
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Jul 2015 (actual)
- Primary completion
- 7 Sep 2018 (actual)
- Study completion
- 7 Sep 2018 (actual)
- First posted
- 11 Apr 2016 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Morphine dosing | Experimental | Other: Morphine pharmacokinetic evaluationEvaluating morphine pharmacokinetics (PK) in 3 groups: normal controls, children with severe OSAS, and obese children with OSAS. Morphine is dosed on ideal body weight in obese children, as recommended by manufacturer. Biomarkers were taken from patients to evaluate their relation to changes in morphine PK. |
Who may qualify
- Ages
- 5 to 12 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Child presenting for surgery that will require opioids
- Age between 5 -12 years of age
- Pre-operative polysomnography study conducted prior to day of surgery
- Body weight >95th percentile for age.
Key exclusion criteria (4 listed)
- 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.)
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 |
|---|---|---|
| Morphine pharmacokinetic evaluationEach group received morphine and blood drawn to evaluate morphine PK | Other | Morphine dosing |
Primary outcome
Plasma Morphine Area Under the Curve (AUC)
Time frame: Through study completion, up to 24 hours after study initiation
To determine changes in morphine AUC due to obesity and OSAS
Maximum Plasma Morphine Concentration (Cmax)
Time frame: Through study completion, up to 24 hours after study initiation
To determine changes in morphine Cmax due to obesity and OSAS
Time to Maximum Plasma Morphine Concentration (Tmax)
Time frame: Through study completion, up to 24 hours after study initiation
To determine changes in morphine Tmax due to obesity and OSAS
Half Life of Plasma Morphine Concentration (T1/2)
Time frame: Through study completion, up to 24 hours after study initiation
To determine changes in morphine T1/2 due to obesity and OSAS
Plasma Morphine Clearance (Cl)
Time frame: Through study completion, up to 24 hours after study initiation
To determine changes in morphine Cl due to obesity and OSAS
Plasma Morphine Volume of Distribution (Vd)
Time frame: Through study completion, up to 24 hours after study initiation
To determine changes in morphine Vd due to obesity and OSAS
Plasma Morphine 3-glucuronide (M3G) Maximum Plasma Concentration (Cmax)
Time frame: Through study completion, up to 24 hours after study initiation
To determine changes in M3G Cmax due to obesity and OSAS
Time to Maximum Morphine 3-glucuronide (M3G) Concentration (Tmax)
Time frame: Through study completion, up to 24 hours after study initiation
To determine changes in M3G Tmax due to obesity and OSAS
Morphine 3-glucuronide (M3G) to Morphine ratio
Time frame: Through study completion, up to 24 hours after study initiation
To determine changes in metabolism of morphine due to obesity and OSAS
Morphine 3-glucuronide (M3G) to Morphine 6-glucuronide (M6G) ratio
Time frame: Through study completion, up to 24 hours after study initiation
To determine changes in metabolism of morphine due to obesity and OSAS
1 secondary outcome
Biomarker concentrations
Time frame: Through study completion, up to 24 hours after study initiation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2019.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Morphine pharmacokinetic evaluation in people with Pediatric Sleep Apnea and Obesity, run by Johns Hopkins 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 6 inclusion and 4 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: finished, as of the sponsor's last update on 9 Sep 2019. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Plasma Morphine Area Under the Curve (AUC) (time frame: Through study completion, up to 24 hours after study initiation). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Sep 2019.