PainNCT01495611
Multicenter Perioperative Opioid Pharmacogenetic Study
An observational study of Pain, run by Children's Hospital Medical Center, Cincinnati at 15 sites in United States.
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 respond to pain medication. Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Pain
- How many people
- 1,000 participants
- Where
- 15 sitesUnited States
- Study dates
- Nov 2010to 30 Apr 2017
- Phase
- Observational
- 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 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Study population: Children undergoing adenotonsillectomy in the United States.
Who may be able to join
- children 6-17 years of age
- ASA physical status 1 and 2
- scheduled for tonsillectomy (T) and tonsillectomy and adenoidectomy (T and A)
- Children with obstructive sleep apnea will also be included.
Who cannot join
- children with developmental delay
- liver and renal diseases,
- preoperative pain requiring analgesics (e.g. chronic tonsillitis).
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109
The Johns Hopkins Hospital
Baltimore, Maryland, 21287
Boston Children's Hospital
Boston, Massachusetts, 02115
Children's Memorial Hospital
Chicago, Illinois, 60614
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
The Children's Hospital, Denver
Denver, Colorado, 80045
Texas Children's Hospital
Houston, Texas, 77094
Children's Hospital of Los Angeles
Los Angeles, California, 90027
UW Health-American Family Children's Hospital
Madison, Wisconsin, 53792
University of Miami - Miller School of Medicine
Miami, Florida, 33136
Ochsner Medical Center for Children
New Orleans, Louisiana, 70121
Stanford University Medical Center
Palo Alto, California, 94304
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Seattle Children's Hospital
Seattle, Washington, 98105
St. Louis Children's Hospital
St Louis, Missouri, 63110
About this study
Official title: Predicting Perioperative Opioid Adverse Effects and Personalizing Analgesia in Children: A Multicenter Pharmacogenetic Study
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 respond to pain medication. Specifically, the investigators want to study factors that may be associated with pain sensitivity, morphine requirement after surgery and side-effects from morphine and other pain medications. The investigators expect that the information obtained in this research study will help us to develop more effective, safe, and tailored treatment options in the future.
Read the detailed description
Opioid drugs as a group have withstood the test of time in their ability to relieve pain. Morphine is the most frequently used "gold standard" opioid for managing surgical pain. Like other opioids, morphine has a narrow therapeutic index and a large inter-patient variability in response. Certain genetic and non-genetic factors are believed to be responsible for variations in analgesic responses and side effects with morphine. Genetic factors determining an individual's pain sensitivity and regulating morphine's pharmacokinetics (transporters) and pharmacodynamics (receptors and signal transduction elements) are likely contributors to such variability. Frequent variations in analgesic response are unfortunately clinically significant with inadequate pain relief at one end of the spectrum of responses and major side effects including potentially fatal respiratory depression due to relative overdosing at the other end. Much of the inter-individual variability in response to a dose of morphine following surgical procedures can be explained by single nucleotide polymorphisms (SNPs) in a subset of the genes that encode proteins involved in pain perception, opioid transport and opioid receptor signaling. The genetic variants of mu opioid receptor (OPRM1), Catechol-O-methyltransferase (COMT), the Multi Drug Resistance Transport protein gene ABC B1, have been associated in small adult studies with varying levels of pain sensitivity, analgesic response to opioids and susceptibility to serious side-effects of opioids such as respiratory depression, sedation and vomiting. Effective and safe acute postoperative pain relief in a subset of children is clinically difficult due to frequent clinical variations in perceptions of pain and responses to opioids. To the investigator's knowledge, there is no other study attempting to individualize perioperative analgesia in children. The investigator's long term goal is to identify factors that modify pain sensitivity and responses to morphine in order to develop more effective, safe and tailored therapies. The overall objective of this application is to evaluate the contribution of individual and combined affects of genetic polymorphisms in OPRM1, COMT and ABC B1 genes and their association with postoperative pain relief and adverse effects with morphine. The investigator's central hypothesis is that specific genetic polymorphisms in genes involved in pain perception, opioid transport and opioid receptor signaling pathways contribute significantly to pain sensitivity, morphine consumption, and morphine's side-effects in children.
This study will also explore a set of other important SNPs that might influence pain perception and responses to morphine in children. The data will be analyzed looking at pain scores, morphine doses, incidence of side-effects of morphine including respiratory depression, sedation, vomiting and itching.
- Conditions
- Pain
- Keywords
- postoperative,, pediatric, pharmacogenetic, opioid, morphine, perioperative, respiratory depression
- Medical subject headings
- Pain, Respiratory Insufficiency
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Outcomes
Incidence of serious opioid related adverse effects including respiratory depression, excessive sedation, nausea and vomiting in recovery room.
Measured: Post-anesthetic recovery room, an expected average of 2 hours
Secondary outcomes (3)
Efficacy Outcome Measures - Opioid interventions
Number of opioid interventions required in the recovery room
Measured: Post-anesthetic recovery room, an expected average of 2 hours
Efficacy Outcome Measures - Opioid requirement
Total opioid requirement will be measured
Measured: Post-anesthetic recovery room, an expected average of 2 hours
Efficacy Outcome Measures - Pain Scores
Pain scores as measured by the Numerical Rating Scale (NRS) and the Facial expression, Leg movement, Activity, Cry, and Consolability (FLACC) Scale
Measured: Post-anesthetic recovery room, an expected average of 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2011 (estimated)
- Study startNov 2010
- Primary completionJan 2016
- Study completion30 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (41)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Baylor College of Medicine, Ochsner Health System, Children's Hospital Colorado, Children's Hospital Los Angeles, C.S. Mott Children's Hospital, St. Christopher's Hospital for Children, St. Louis Children's Hospital, Boston Children's Hospital, Seattle Children's Hospital, Ann & Robert H Lurie Children's Hospital of Chicago, University of Wisconsin, Madison, University of Miami, Johns Hopkins University, Stanford University, Phoenix Children's Hospital, University of Michigan, University of Utah, Shanghai Children's Hospital
- Responsible party
- Sponsor
- Investigators
- Senthilkumar Sadhasivam, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01495611
- Sponsor's protocol ID
- 2010-1353
- Status last verified
- Jan 2017
- First submitted
- 12 Dec 2011
- Last updated
- 31 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, Belfer I, Goldman D, Xu K, Shabalina SA, Shagin D, Max MB, Makarov SS, Maixner W. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet. 2005 Jan 1;14(1):135-43. doi: 10.1093/hmg/ddi013. Epub 2004 Nov 10.
PubMed 15537663Chou WY, Wang CH, Liu PH, Liu CC, Tseng CC, Jawan B. Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy. Anesthesiology. 2006 Aug;105(2):334-7. doi: 10.1097/00000542-200608000-00016.
PubMed 16871067Oertel BG, Schmidt R, Schneider A, Geisslinger G, Lotsch J. The mu-opioid receptor gene polymorphism 118A>G depletes alfentanil-induced analgesia and protects against respiratory depression in homozygous carriers. Pharmacogenet Genomics. 2006 Sep;16(9):625-36. doi: 10.1097/01.fpc.0000220566.90466.a2.
PubMed 16906017Sutters KA, Miaskowski C. Inadequate pain management and associated morbidity in children at home after tonsillectomy. J Pediatr Nurs. 1997 Jun;12(3):178-85. doi: 10.1016/S0882-5963(97)80075-9.
PubMed 9198341Sutters KA, Miaskowski C, Holdridge-Zeuner D, Waite S, Paul SM, Savedra MC, Lanier B. A randomized clinical trial of the effectiveness of a scheduled oral analgesic dosing regimen for the management of postoperative pain in children following tonsillectomy. Pain. 2004 Jul;110(1-2):49-55. doi: 10.1016/j.pain.2004.03.008.
PubMed 15275751Hamers JP, Abu-Saad HH. Children's pain at home following (adeno) tonsillectomy. Eur J Pain. 2002;6(3):213-9. doi: 10.1053/eujp.2001.0326.
PubMed 12036308Homer JJ, Frewer JD, Swallow J, Semple P. An audit of post-operative analgesia in children following tonsillectomy. J Laryngol Otol. 2002 May;116(5):367-70. doi: 10.1258/0022215021910807.
PubMed 12080995Homer JJ, Swallow J, Semple P. Audit of pain management at home following tonsillectomy in children. J Laryngol Otol. 2001 Mar;115(3):205-8. doi: 10.1258/0022215011907208.
PubMed 11244527Huth MM, Broome ME. A snapshot of children's postoperative tonsillectomy outcomes at home. J Spec Pediatr Nurs. 2007 Jul;12(3):186-95. doi: 10.1111/j.1744-6155.2007.00111.x.
PubMed 17594298Huth MM, Broome ME, Good M. Imagery reduces children's post-operative pain. Pain. 2004 Jul;110(1-2):439-48. doi: 10.1016/j.pain.2004.04.028.
PubMed 15275797Gedaly-Duff V, Ziebarth D. Mothers' management of adenoid-tonsillectomy pain in 4- to 8-year-olds: a preliminary study. Pain. 1994 Jun;57(3):293-299. doi: 10.1016/0304-3959(94)90004-3.
PubMed 7524009Warnock FF, Lander J. Pain progression, intensity and outcomes following tonsillectomy. Pain. 1998 Mar;75(1):37-45. doi: 10.1016/S0304-3959(97)00202-9.
PubMed 9539672Burkart CM, Steward DL. Antibiotics for reduction of posttonsillectomy morbidity: a meta-analysis. Laryngoscope. 2005 Jun;115(6):997-1002. doi: 10.1097/01.MLG.0000163749.77019.8F.
PubMed 15933509Perquin CW, Hazebroek-Kampschreur AAJM, Hunfeld JAM, Bohnen AM, van Suijlekom-Smit LWA, Passchier J, van der Wouden JC. Pain in children and adolescents: a common experience. Pain. 2000 Jul;87(1):51-58. doi: 10.1016/S0304-3959(00)00269-4.
PubMed 10863045Duedahl TH, Hansen EH. A qualitative systematic review of morphine treatment in children with postoperative pain. Paediatr Anaesth. 2007 Aug;17(8):756-74. doi: 10.1111/j.1460-9592.2007.02213.x.
PubMed 17596221
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predicting Perioperative Opioid Adverse Effects and Personalizing Analgesia in Children: A Multicenter Pharmacogenetic Study
- ClinicalTrials.gov ID
- NCT01495611
- Acronym / sponsor ID
- 2010-1353
- Conditions
- Pain
- Keywords
- postoperative,, pediatric, pharmacogenetic, opioid, morphine, perioperative, respiratory depression
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,000 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Baylor College of Medicine, Ochsner Health System, Children's Hospital Colorado, Children's Hospital Los Angeles, C.S. Mott Children's Hospital, St. Christopher's Hospital for Children, St. Louis Children's Hospital, Boston Children's Hospital, Seattle Children's Hospital, Ann & Robert H Lurie Children's Hospital of Chicago, University of Wisconsin, Madison, University of Miami, Johns Hopkins University, Stanford University, Phoenix Children's Hospital, University of Michigan, University of Utah, Shanghai Children's Hospital
- Study start
- Nov 2010 (actual)
- Primary completion
- Jan 2016 (actual)
- Study completion
- 30 Apr 2017
- First posted
- 20 Dec 2011 (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.
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 respond to pain medication. Specifically, the investigators want to study factors that may be associated with pain sensitivity, morphine requirement after surgery and side-effects from morphine and other pain medications. The investigators expect that the information obtained in this research study will help us to develop more effective, safe, and tailored treatment options in the future.
Detailed description
Opioid drugs as a group have withstood the test of time in their ability to relieve pain. Morphine is the most frequently used "gold standard" opioid for managing surgical pain. Like other opioids, morphine has a narrow therapeutic index and a large inter-patient variability in response. Certain genetic and non-genetic factors are believed to be responsible for variations in analgesic responses and side effects with morphine. Genetic factors determining an individual's pain sensitivity and regulating morphine's pharmacokinetics (transporters) and pharmacodynamics (receptors and signal transduction elements) are likely contributors to such variability. Frequent variations in analgesic response are unfortunately clinically significant with inadequate pain relief at one end of the spectrum of responses and major side effects including potentially fatal respiratory depression due to relative overdosing at the other end. Much of the inter-individual variability in response to a dose of morphine following surgical procedures can be explained by single nucleotide polymorphisms (SNPs) in a subset of the genes that encode proteins involved in pain perception, opioid transport and opioid receptor signaling. The genetic variants of mu opioid receptor (OPRM1), Catechol-O-methyltransferase (COMT), the Multi Drug Resistance Transport protein gene ABC B1, have been associated in small adult studies with varying levels of pain sensitivity, analgesic response to opioids and susceptibility to serious side-effects of opioids such as respiratory depression, sedation and vomiting. Effective and safe acute postoperative pain relief in a subset of children is clinically difficult due to frequent clinical variations in perceptions of pain and responses to opioids. To the investigator's knowledge, there is no other study attempting to individualize perioperative analgesia in children. The investigator's long term goal is to identify factors that modify pain sensitivity and responses to morphine in order to develop more effective, safe and tailored therapies. The overall objective of this application is to evaluate the contribution of individual and combined affects of genetic polymorphisms in OPRM1, COMT and ABC B1 genes and their association with postoperative pain relief and adverse effects with morphine. The investigator's central hypothesis is that specific genetic polymorphisms in genes involved in pain perception, opioid transport and opioid receptor signaling pathways contribute significantly to pain sensitivity, morphine consumption, and morphine's side-effects in children.
This study will also explore a set of other important SNPs that might influence pain perception and responses to morphine in children. The data will be analyzed looking at pain scores, morphine doses, incidence of side-effects of morphine including respiratory depression, sedation, vomiting and itching.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Children undergoing adenotonsillectomy in the United States.
Key inclusion criteria (4 listed)
- children 6-17 years of age
- ASA physical status 1 and 2
- scheduled for tonsillectomy (T) and tonsillectomy and adenoidectomy (T and A)
- Children with obstructive sleep apnea will also be included.
Key exclusion criteria (3 listed)
- children with developmental delay
- liver and renal diseases,
- preoperative pain requiring analgesics (e.g. chronic tonsillitis).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Safety Outcomes
Time frame: Post-anesthetic recovery room, an expected average of 2 hours
Incidence of serious opioid related adverse effects including respiratory depression, excessive sedation, nausea and vomiting in recovery room.
3 secondary outcomes
Efficacy Outcome Measures - Opioid interventions
Time frame: Post-anesthetic recovery room, an expected average of 2 hours
Efficacy Outcome Measures - Opioid requirement
Time frame: Post-anesthetic recovery room, an expected average of 2 hours
Efficacy Outcome Measures - Pain Scores
Time frame: Post-anesthetic recovery room, an expected average of 2 hours
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 31 Jan 2017.
- Background: PubMed 15537663Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, Belfer I, Goldman D, Xu K, Shabalina SA, Shagin D, Max MB, Makarov SS, Maixner W. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet. 2005 Jan 1;14(1):135-43. doi: 10.1093/hmg/ddi013. Epub 2004 Nov 10.
- Background: PubMed 16871067Chou WY, Wang CH, Liu PH, Liu CC, Tseng CC, Jawan B. Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy. Anesthesiology. 2006 Aug;105(2):334-7. doi: 10.1097/00000542-200608000-00016.
- Background: PubMed 16906017Oertel BG, Schmidt R, Schneider A, Geisslinger G, Lotsch J. The mu-opioid receptor gene polymorphism 118A>G depletes alfentanil-induced analgesia and protects against respiratory depression in homozygous carriers. Pharmacogenet Genomics. 2006 Sep;16(9):625-36. doi: 10.1097/01.fpc.0000220566.90466.a2.
- Background: PubMed 9198341Sutters KA, Miaskowski C. Inadequate pain management and associated morbidity in children at home after tonsillectomy. J Pediatr Nurs. 1997 Jun;12(3):178-85. doi: 10.1016/S0882-5963(97)80075-9.
- Background: PubMed 15275751Sutters KA, Miaskowski C, Holdridge-Zeuner D, Waite S, Paul SM, Savedra MC, Lanier B. A randomized clinical trial of the effectiveness of a scheduled oral analgesic dosing regimen for the management of postoperative pain in children following tonsillectomy. Pain. 2004 Jul;110(1-2):49-55. doi: 10.1016/j.pain.2004.03.008.
- Background: PubMed 12036308Hamers JP, Abu-Saad HH. Children's pain at home following (adeno) tonsillectomy. Eur J Pain. 2002;6(3):213-9. doi: 10.1053/eujp.2001.0326.
- Background: PubMed 12080995Homer JJ, Frewer JD, Swallow J, Semple P. An audit of post-operative analgesia in children following tonsillectomy. J Laryngol Otol. 2002 May;116(5):367-70. doi: 10.1258/0022215021910807.
- Background: PubMed 11244527Homer JJ, Swallow J, Semple P. Audit of pain management at home following tonsillectomy in children. J Laryngol Otol. 2001 Mar;115(3):205-8. doi: 10.1258/0022215011907208.
- Background: PubMed 17594298Huth MM, Broome ME. A snapshot of children's postoperative tonsillectomy outcomes at home. J Spec Pediatr Nurs. 2007 Jul;12(3):186-95. doi: 10.1111/j.1744-6155.2007.00111.x.
- Background: PubMed 15275797Huth MM, Broome ME, Good M. Imagery reduces children's post-operative pain. Pain. 2004 Jul;110(1-2):439-48. doi: 10.1016/j.pain.2004.04.028.
- Background: PubMed 7524009Gedaly-Duff V, Ziebarth D. Mothers' management of adenoid-tonsillectomy pain in 4- to 8-year-olds: a preliminary study. Pain. 1994 Jun;57(3):293-299. doi: 10.1016/0304-3959(94)90004-3.
- Background: PubMed 9539672Warnock FF, Lander J. Pain progression, intensity and outcomes following tonsillectomy. Pain. 1998 Mar;75(1):37-45. doi: 10.1016/S0304-3959(97)00202-9.
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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.
Senthilkumar Sadhasivam principal investigator
Children's Hospital Medical Center, Cincinnati
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pain, run by Children's Hospital Medical Center, Cincinnati at 15 sites 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 4 inclusion and 3 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 31 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites 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?
Safety Outcomes (time frame: Post-anesthetic recovery room, an expected average of 2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01495611, which also lists 41 linked publications.
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 31 Jan 2017.