PainPIUONCT03464773
Pain and Irritability in Non-Verbal Children
A study testing PIUO Pathway in people with Pain and Neuropathic Pain, run by University of British Columbia at 1 site in Canada.
Trial summary
Children born with severe brain-based developmental disabilities frequently experience persistent unexplained periods of pain and irritability, often compounded by a limited capacity to communicate their distress. The investigators call this entity Pain and Irritability of Unknown Origin (PIUO). Read more about this study
- Who is it for?
- Ages 6 months to 18 years
- Conditions the study is for
- Pain, Neuropathic Pain, Irritability
- What is being tested?
- PIUO Pathway
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteCanada
- Study dates
- 15 Apr 2018to 31 Jul 2023
- 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 6 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children aged 6 months to 18 years with SNI (from any cause) with unexplained pain and irritability and whose cognitive or communication impairments prevent determination of pain location, cause, and type will be eligible to participate.
- Eligible children will have cognitive impairment or be non-verbal and have severe levels of disability equivalent to Gross Motor Functional Classification System (GMFCS) scores of 3, 4 or 5.
- Eligible children will score >3 on two scales administered via an Eligibility Screening that measures persistence and distress level the child is experiencing as well as identifies the type of pain and irritability as PIUO - with no obvious cause or explanation. The score of >3 on the scale measuring pain persistence and distress level confirms that the child is experiencing pain and irritability more than "a little" on "some days".
- Parents should have sufficient English/French language skill, or have access to assistance, to participate in the clinic visits and complete survey tools.
Who cannot join
- Children not within the specified age range
- Children with communication capabilities and cognitive development to localize their pain
- Children that have an explained and treatable cause of pain and irritability.
- Parents who do not speak one of Canada's two official languages (English or French)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Optimizing the Management of Pain and Irritability of Unknown Origin (PIUO) in Children With Severe Neurological Impairment
Children born with severe brain-based developmental disabilities frequently experience persistent unexplained periods of pain and irritability, often compounded by a limited capacity to communicate their distress. The investigators call this entity Pain and Irritability of Unknown Origin (PIUO). The investigators have designed a systematic approach, called the PIUO Pathway, to address the management of these children's pain and irritability with the goals of reducing pain symptoms, improving the day-to-day lives of the child and family, and simplifying treatment options for clinicians.
Read the detailed description
The purpose of this project is to develop, test, and disseminate an approach to reducing and resolving pain in children with developmental brain disorders, specifically those with severe neurological impairments (SNI). It focuses on the problem of ongoing, unexplained, and difficult-to-treat pain and irritability that many children with SNI, and their families, experience over time. The goal is to improve the assessment and treatment of pain and irritability in children diagnosed with complex health conditions and multiple disabilities, who have limited communication and cognition.
The plan is to evaluate the effectiveness of an integrated clinical pathway (i.e. a sequential order of standardized evaluation steps) for managing unexplained pain and irritability in these vulnerable children.
BACKGROUND Pain is the most common symptom reported by the parents and caregivers of children with SNI, however, pain is notoriously difficult to identify, and therefore treat, in non-verbal children because their signals of distress are ambiguous and hard to decode. Typical distress behaviours include crying, tears, facial grimace, limb withdrawal, arching, hypertonicity, and decreased sleep. More mobile children may curl up into a ball, fling their arms or legs, or engage in self-injurious behaviour; conversely they may display decreased activity.
Children with SNI may experience nociceptive-inflammatory pain as a result of their specific medical condition (e.g. joint contractures) or from many procedures that they experience (e.g. injections). Often, however, it is not clear what underlies the pain behavior. Parents are experts in identifying pain behaviours in their own child, but consider their interpretation to be a complex and uncertain process. As well, while pain behaviours can be described by clinicians and parents, the behaviours themselves are subjective, ambiguous, and can reflect a variety of problems in addition to pain. Unless an obvious nociceptive-inflammatory trigger such as an injury is witnessed, parents and clinicians find it very difficult to ascribe all of the pain-like behaviours observed in children with SNI to pain as defined by the International Association for the Study of Pain (IASP). In this context, the term "pain" does not serve as a descriptive label. Therefore, the investigators describe pain behaviour episodes using a less deterministic term, "pain and irritability," acknowledging that the behaviour is certainly negative in the eyes of the witnessing caregiver. The team has defined this entity as Pain and Irritability of Unknown Origin (PIUO).
HYPOTHESIS The overall hypothesis is that children participating in the PIUO Pathway will experience improvement or resolution of PIUO from baseline to post-study, compared to children receiving treatment as usual while on the waitlist.
The goal is to improve PIUO beyond what has been undertaken by the child's usual clinical teams. The primary outcome is improved pain control for non-verbal children with SNI as shown in a reduction of pain and irritability episodes and their severity. Secondary outcomes include decreased pain severity; improved family quality of life and ease of implementation of the PIUO Pathway for clinicians.
STUDY DESIGN Interventions for resolving PIUO are time- and resource-intensive. They require a focused approach to assessing all the underlying possibilities for the PIUO and addressing each potential source of pain one at a time. Tackling PIUO requires systematic, comprehensive, process-oriented thinking applied by an interdisciplinary team with flexibility in terms of approach and time. There have been recommendations in the literature about how to approach the problem of PIUO in children with SNI, but these recommendations have never been subjected to systemic evaluation as complex interventions, for example by following an integrated clinical pathway.
Integrated clinical pathways (also called "care pathways" or "critical pathways") are structured, sequenced approaches guiding the delivery of healthcare, often with a multidisciplinary perspective. They provide algorithms to be followed in the assessment and treatment of conditions, but are not intended to be rigidly followed; instead, integrated clinical pathways delineate a foundation for a clinician's approach to a complex problem, thereby avoiding inefficiencies in evaluation or resource use. Integrated clinical pathways are a form of Complex Interventions and have been developed for sickle cell pain, childhood asthma, appendicitis, autoimmune conditions, in-born errors of metabolism, and cerebrospinal fluid shunt management. Despite their complexity, integrated clinical pathways are appropriate interventions for evaluation by Randomized Controlled Trial (RCT). RCTs of integrated clinical pathways have been proposed and/or completed for complex, multi-factorial patient problems including lung disease, heart failure, gastrointestinal surgery, stroke, and hip fractures.
In this study, the investigators will use a waitlist-controlled RCT design, with 120 children randomized to PIUO Pathway or waitlist (standard care) treatment arms. This design was chosen strategically, with consideration of both the special pediatric population being studied and the ethical inappropriateness of randomly assigning children to a placebo group when pain is the target condition.
- Conditions
- Pain, Neuropathic Pain, Irritability
- Being tested
- PIUO Pathway
- Medical subject headings
- Pain, Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PIUO PathwayOther
See arm descriptions
| Study group | Role | What they receive |
|---|---|---|
| Pathway | Other | The PIUO Pathway is implemented by clinicians (MD and RN) with expertise in treating pain in children. Each participant proceeds through the PIUO Pathway as long as their pain persists, but will exit the PIUO Pathway at any stage in case their pain is resolved. The Pathway has two steps: Step 1 is a thorough history and patient evaluation, including directed testing. Step 2 is a series of screening tests to further explore any potential underlying disease or injury not apparent based on history and physical examination. Receives: Other: PIUO Pathway |
| Waitlist | No intervention | Participants randomized to the Waitlist will cross over to the Pathway after 8 weeks. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of pain severity of children on the pathway
Number of participants whose pain scores rank in the lower pain categories (category A or B) as compared to the proportion of those on the waitlist group, measured by the parent-reported Pain Survey.
Measured: Week 10
Secondary outcomes (5)
Identification of causes of pain and irritability of unknown origin in non-verbal children
Number of children with known causes of pain and irritability at end of pathway
Measured: End of Pathway (up to 8 months post-baseline)
Decreased pain & irritability scores for children over time
Pain Survey (baseline score compared to End of Pathway score)
Measured: Baseline and End of Pathway (up to 8 months post-baseline)
Improvement in parent fatigue levels
Parent-reported reduction in fatigue levels on the Patient-Reported Outcomes Measurement Information System (PROMIS-57: Fatigue 8a subscale Max. 40 to Min. 8- higher values worse) from baseline fatigue score compared to End of Pathway score
Measured: Baseline and End of Pathway (up to 8 months post-baseline)
Recorded time commitment for clinical team to implement PIUO Pathway
Average hours of clinical time for MD + RD involved to complete the study per patient
Measured: Baseline and End of Pathway (up to 8 months post-baseline)
Benefit ranking of ongoing communication with study research nurse
Number of parents rating the communication with the nurse as "valuable" as per the Family feedback form.
Measured: End of Pathway (up to 8 months post-baseline)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2018
- Study start15 Apr 2018
- Primary completion31 Jul 2023
- Study completion31 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe 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
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), University of Calgary, University of Ottawa, Provincial Health Services Authority British Columbia, Alberta Children's Hospital, Children's Hospital of Eastern Ontario, The Hospital for Sick Children
- Responsible party
- Principal investigator, Harold Siden, University of British Columbia
- Investigators
- Hal Siden, MD, Principal investigator, BC Children's Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03464773
- Sponsor's protocol ID
- H16-03288
- Acronym
- PIUO
- Status last verified
- May 2024
- First submitted
- 25 Jan 2018
- Last updated
- 8 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Siden HB, Carleton BC, Oberlander TF. Physician variability in treating pain and irritability of unknown origin in children with severe neurological impairment. Pain Res Manag. 2013 Sep-Oct;18(5):243-8. doi: 10.1155/2013/193937. Epub 2013 Jul 24.
PubMed 23885348
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimizing the Management of Pain and Irritability of Unknown Origin (PIUO) in Children With Severe Neurological Impairment
- ClinicalTrials.gov ID
- NCT03464773
- Acronym / sponsor ID
- PIUO / H16-03288
- Conditions
- Pain, Neuropathic Pain, Irritability
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), University of Calgary, University of Ottawa, Provincial Health Services Authority British Columbia, Alberta Children's Hospital, Children's Hospital of Eastern Ontario, The Hospital for Sick Children
- Study start
- 15 Apr 2018 (actual)
- Primary completion
- 31 Jul 2023 (actual)
- Study completion
- 31 Jul 2023 (actual)
- First posted
- 14 Mar 2018 (actual)
- 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.
Children born with severe brain-based developmental disabilities frequently experience persistent unexplained periods of pain and irritability, often compounded by a limited capacity to communicate their distress. The investigators call this entity Pain and Irritability of Unknown Origin (PIUO). The investigators have designed a systematic approach, called the PIUO Pathway, to address the management of these children's pain and irritability with the goals of reducing pain symptoms, improving the day-to-day lives of the child and family, and simplifying treatment options for clinicians.
Detailed description
The purpose of this project is to develop, test, and disseminate an approach to reducing and resolving pain in children with developmental brain disorders, specifically those with severe neurological impairments (SNI). It focuses on the problem of ongoing, unexplained, and difficult-to-treat pain and irritability that many children with SNI, and their families, experience over time. The goal is to improve the assessment and treatment of pain and irritability in children diagnosed with complex health conditions and multiple disabilities, who have limited communication and cognition.
The plan is to evaluate the effectiveness of an integrated clinical pathway (i.e. a sequential order of standardized evaluation steps) for managing unexplained pain and irritability in these vulnerable children.
BACKGROUND Pain is the most common symptom reported by the parents and caregivers of children with SNI, however, pain is notoriously difficult to identify, and therefore treat, in non-verbal children because their signals of distress are ambiguous and hard to decode. Typical distress behaviours include crying, tears, facial grimace, limb withdrawal, arching, hypertonicity, and decreased sleep. More mobile children may curl up into a ball, fling their arms or legs, or engage in self-injurious behaviour; conversely they may display decreased activity.
Children with SNI may experience nociceptive-inflammatory pain as a result of their specific medical condition (e.g. joint contractures) or from many procedures that they experience (e.g. injections). Often, however, it is not clear what underlies the pain behavior. Parents are experts in identifying pain behaviours in their own child, but consider their interpretation to be a complex and uncertain process. As well, while pain behaviours can be described by clinicians and parents, the behaviours themselves are subjective, ambiguous, and can reflect a variety of problems in addition to pain. Unless an obvious nociceptive-inflammatory trigger such as an injury is witnessed, parents and clinicians find it very difficult to ascribe all of the pain-like behaviours observed in children with SNI to pain as defined by the International Association for the Study of Pain (IASP). In this context, the term "pain" does not serve as a descriptive label. Therefore, the investigators describe pain behaviour episodes using a less deterministic term, "pain and irritability," acknowledging that the behaviour is certainly negative in the eyes of the witnessing caregiver. The team has defined this entity as Pain and Irritability of Unknown Origin (PIUO).
HYPOTHESIS The overall hypothesis is that children participating in the PIUO Pathway will experience improvement or resolution of PIUO from baseline to post-study, compared to children receiving treatment as usual while on the waitlist.
The goal is to improve PIUO beyond what has been undertaken by the child's usual clinical teams. The primary outcome is improved pain control for non-verbal children with SNI as shown in a reduction of pain and irritability episodes and their severity. Secondary outcomes include decreased pain severity; improved family quality of life and ease of implementation of the PIUO Pathway for clinicians.
STUDY DESIGN Interventions for resolving PIUO are time- and resource-intensive. They require a focused approach to assessing all the underlying possibilities for the PIUO and addressing each potential source of pain one at a time. Tackling PIUO requires systematic, comprehensive, process-oriented thinking applied by an interdisciplinary team with flexibility in terms of approach and time. There have been recommendations in the literature about how to approach the problem of PIUO in children with SNI, but these recommendations have never been subjected to systemic evaluation as complex interventions, for example by following an integrated clinical pathway.
Integrated clinical pathways (also called "care pathways" or "critical pathways") are structured, sequenced approaches guiding the delivery of healthcare, often with a multidisciplinary perspective. They provide algorithms to be followed in the assessment and treatment of conditions, but are not intended to be rigidly followed; instead, integrated clinical pathways delineate a foundation for a clinician's approach to a complex problem, thereby avoiding inefficiencies in evaluation or resource use. Integrated clinical pathways are a form of Complex Interventions and have been developed for sickle cell pain, childhood asthma, appendicitis, autoimmune conditions, in-born errors of metabolism, and cerebrospinal fluid shunt management. Despite their complexity, integrated clinical pathways are appropriate interventions for evaluation by Randomized Controlled Trial (RCT). RCTs of integrated clinical pathways have been proposed and/or completed for complex, multi-factorial patient problems including lung disease, heart failure, gastrointestinal surgery, stroke, and hip fractures.
In this study, the investigators will use a waitlist-controlled RCT design, with 120 children randomized to PIUO Pathway or waitlist (standard care) treatment arms. This design was chosen strategically, with consideration of both the special pediatric population being studied and the ethical inappropriateness of randomly assigning children to a placebo group when pain is the target condition.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pathway | Other | Other: PIUO PathwayThe PIUO Pathway is implemented by clinicians (MD and RN) with expertise in treating pain in children. Each participant proceeds through the PIUO Pathway as long as their pain persists, but will exit the PIUO Pathway at any stage in case their pain is resolved. The Pathway has two steps: Step 1 is a thorough history and patient evaluation, including directed testing. Step 2 is a series of screening tests to further explore any potential underlying disease or injury not apparent based on history and physical examination. |
| Waitlist | No intervention | –Participants randomized to the Waitlist will cross over to the Pathway after 8 weeks. |
Who may qualify
- Ages
- 6 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Children aged 6 months to 18 years with SNI (from any cause) with unexplained pain and irritability and whose cognitive or communication impairments prevent determination of pain location, cause, and type will be eligible to participate.
- Eligible children will have cognitive impairment or be non-verbal and have severe levels of disability equivalent to Gross Motor Functional Classification System (GMFCS) scores of 3, 4 or 5.
- Eligible children will score >3 on two scales administered via an Eligibility Screening that measures persistence and distress level the child is experiencing as well as identifies the type of pain and irritability as PIUO - with no obvious cause or explanation. The score of >3 on the scale measuring pain persistence and distress level confirms that the child is experiencing pain and irritability more than "a little" on "some days".
- Parents should have sufficient English/French language skill, or have access to assistance, to participate in the clinic visits and complete survey tools.
Key exclusion criteria (4 listed)
- Children not within the specified age range
- Children with communication capabilities and cognitive development to localize their pain
- Children that have an explained and treatable cause of pain and irritability.
- Parents who do not speak one of Canada's two official languages (English or French)
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 |
|---|---|---|
| PIUO PathwaySee arm descriptions | Other | Pathway |
Primary outcome
Reduction of pain severity of children on the pathway
Time frame: Week 10
Number of participants whose pain scores rank in the lower pain categories (category A or B) as compared to the proportion of those on the waitlist group, measured by the parent-reported Pain Survey.
5 secondary outcomes
Identification of causes of pain and irritability of unknown origin in non-verbal children
Time frame: End of Pathway (up to 8 months post-baseline)
Decreased pain & irritability scores for children over time
Time frame: Baseline and End of Pathway (up to 8 months post-baseline)
Improvement in parent fatigue levels
Time frame: Baseline and End of Pathway (up to 8 months post-baseline)
Recorded time commitment for clinical team to implement PIUO Pathway
Time frame: Baseline and End of Pathway (up to 8 months post-baseline)
Benefit ranking of ongoing communication with study research nurse
Time frame: End of Pathway (up to 8 months post-baseline)
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 8 May 2024.
- Background: PubMed 23885348Siden HB, Carleton BC, Oberlander TF. Physician variability in treating pain and irritability of unknown origin in children with severe neurological impairment. Pain Res Manag. 2013 Sep-Oct;18(5):243-8. doi: 10.1155/2013/193937. Epub 2013 Jul 24.
- Study websiteLink provided by the sponsor.
- 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.
Hal Siden, MD principal investigator
BC Children's Hospital Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PIUO Pathway in people with Pain and Neuropathic Pain, run by University of British Columbia at 1 site in Canada.
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 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 8 May 2024. 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 Canada. 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?
Reduction of pain severity of children on the pathway (time frame: Week 10). 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 NCT03464773, which also lists 1 linked publication.
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 8 May 2024; AzTrials last refreshed its copy on 6 Nov 2026.