PainPhase 2NCT04619862
Efficacy of Gabapentin in Treating Pain in Children With SNI (Gabapentin Trial)
A Phase 2 study testing Gabapentin 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?
- Gabapentin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteCanada
- Study dates
- 15 May 2021to 30 Apr 2026
- Phase
- Phase 2
- 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 as well as Communication Function Classification System (CFCS) level 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".
- The will be evidence of a comprehensive evaluation of PIUO in the child's medical history, showing no evidence for treatable sources (nociceptive-inflammatory) of pain and/or irritability symptoms.
Who cannot join
- Children not within the specified age range
- Children with communication capabilities and cognitive development to localize their pain.
- Participants whose pain and or irritability is diagnosed through completion of the PIUO Pathway during the enrollment phase of the trial.
- Patients with a known hypersensitivity/allergy to the study medication
- Patients who are actively participating in another experimental therapy study for pain and/or irritability.
- Patients who are a poor medical risk because of other systemic diseases or active uncontrolled infections.
Show all 13Show fewer
- Patients who score A or B on the Pain Survey
- Patients who have an active source of nociceptive-inflammatory pain at the time of enrolment (e.g., post-operative pain)
- Patients with active renal disease, known renal impairment or glomerular filtration rate < 60 mL/min/1.73 m2 (if known).
- Patients with known significant hepatic impairment at the discretion of the investigator.
- Patients with clinically relevant abnormal ECG (if available) at the discretion of the investigator.
- Patients with diagnosis of sickle cell disease.
- Parents who do not speak one of Canada's two official languages (English or French)
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
BC Children's Hospital
Vancouver, British Columbia, V6H 3N1
Anne-Mette Hermansen
About this study
Official title: Efficacy of Gabapentin in Treating Pain 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 rationale of this trial is to identify the clinical effect size of gabapentin in reducing and resolving pain in children with developmental brain disorders, specifically those with severe neurological impairment (SNI).
Read the detailed description
Background
Children with SNI may experience nociceptive-inflammatory pain as a result of their specific medical condition or procedures. Often, however, it is not clear what underlies the pain behavior as there is no clear inciting noxious event. The investigators define this entity of pain without an obvious source as Pain and Irritability of Unknown Origin (PIUO).
The investigators' work to date has developed an efficient, focused clinical pathway to evaluate children with SNI for all potential sources of nociceptive-inflammatory pain. Using this approach the "unknown" element of pain in these children is reduced and a source of PIUO may be found in individual cases, increasing the potential for treatment. Nevertheless there are children, who at the end of a thorough evaluation guided by a clinical pathway, will still have PIUO. These children may benefit from adjuvant analgesics such as gabapentin.
The evidence base supporting the use of gabapentin for pain and irritability in infants and children with neurological impairment rests on case series publications describing a limited number of retrospective cases. The lack of prospective, randomized studies, even for this commonly used medication, underpins the rationale for this trial.
Objectives
The primary objective of the pilot trial is to evaluate the clinically significant difference of gabapentin to decrease pain and irritability in children with SNI, when the source of pain and irritability is attributed to neurological dysregulation (nociplastic pain), as measured by parent-reported pain scores.
The investigators will compare the gabapentin versus placebo along an escalating dose range for both individual subjects and for the group. The investigators will aggregate the results of the completed N-of-1 trials across all subjects to estimate the group level comparative effectiveness of gabapentin in reducing pain and irritability.
Outcomes from this study will help with designing larger randomized control trials, especially with sample size and power calculations. It will also provide prospective information on drug effect.
Trial Design
This trial uses a single randomized multiple-measures cross-over design (N-of-1), with results aggregated over several subjects. This design is well-suited to outcomes that are highly specific to each individual and not amenable to precise measurement across a large cohort. The heterogenous nature of pain and irritability responses in children are more likely to be personally specific and characteristic, rather than generalizable.
Subjects will switch between gabapentin (G) and placebo (P) in a randomized order. The sequence of whether G precedes P (GP) or P precedes G (PG) will be randomized by the study pharmacist, and neither the clinician nor the subject (parent/caregiver) will know the sequence. Each subject will serve as their own control and experiment, allowing for a finer assessment of the treatment efficacy within each patient.
The primary variable assessed is the child's pain score. Pain and irritability will be measured using the Non-Communicating Children's Pain Checklist - Revised (NCCPC-R) at specified intervals throughout the randomized sequence of G : P. Additional measures of parent/caregiver burden and impact on their daily function will be undertaken weekly with the PROMIS-57, a tool adapted to measure the impact of the child's pain and irritability on parental functioning. Other measures will be of usual, known side effects (e.g., sedation) and of any unexpected adverse events.
- Conditions
- Pain, Neuropathic Pain, Irritability
- Being tested
- Gabapentin, Placebo
- Medical subject headings
- Pain, Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GabapentinDrug
See arm descriptions
PlaceboDrug
See arm descriptions
| Study group | Role | What they receive |
|---|---|---|
| Medication | Experimental | Gabapentin is clinically started at a low dose and titrated to clinical effect or maximum target dose, whichever is lower.
The starting dose of gabapentin will be 5 mg/kg administered as oral liquid or via gastric or jejunal routes. On Day 1 of the study, the gabapentin will be administered once at bedtime and then increased according to a preset schedule. The dose will be increased every 3rd - 4th day in a step wise fashion of 13% - 50%, starting with the evening dose in order to accommodate sedation. The maximum dose for subjects will be as follows: < 15 kg to 60 mg/kg day and ≥15 kg to 45 mg/kg/day. Receives: Drug: Gabapentin |
| Placebo | Placebo comparator | Participants on this arm receive placebo, masked and dispensed according to the same preset schedule as the Medication arm. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean pain and irritability score
The mean pain and irritability score on the Non-Communicating Children's Pain Checklist Revised (NCCPC-R) on active drug compared to placebo.
Measured: Days 11-19
Secondary outcomes (4)
Identification of lowest effective dose
For patients who benefited from gabapentin, identification of the lowest dose that was effective in reducing pain scores, as shown by a lower Non-Communication Children's Pain Checklist - Revised (NCCPC-R) score compared to baseline.
Measured: Days 11-19 on active drug
Maximal effect dosage
For patients who benefited from gabapentin, identification of the maximal effect dosage as measured by the largest improvement in the Non-Communicating Children's Pain Checklist - Revised (NCCPC-R) score compared to baseline.
Measured: Days 11-19 on active drug
Identification of latency time
Identification of the latency time in days to the onset of maximum relief of pain and irritability as measured by the Non-Communication Children's Pain Checklist - Revised (NCCPC-R) score
Measured: Days 0-19
Adverse Events collection
Adverse Events collection demonstrates the AEs on treatment arm do not exceed the frequency found in the Product Monograph for children receiving gabapentin
Measured: Through Sequence 1 and 2, total of 55 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2020
- Study start15 May 2021
- Primary completion31 Mar 2026 (estimated)
- Study completion30 Apr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This trial uses a single randomized multiple-measures cross-over design (N-of-1), with results aggregated over several subjects. In the trial, each patient will switch between gabapentin (G) and placebo (P). The sequence of whether G precedes P (GP) or P precedes G (PG) will be randomized and neither the clinician nor the subject (parent/caregiver) will know the sequence. Each subject will serve as their own control and experiment, allowing for a finer assessment of the treatment efficacy within each patient.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Child-Bright Network, BC Children's Hospital Research Institute
- 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
- NCT04619862
- Sponsor's protocol ID
- H20-02023
- Status last verified
- May 2024
- First submitted
- 27 Oct 2020
- Last updated
- 8 May 2024
- 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 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Gabapentin in Treating Pain in Children With Severe Neurological Impairment
- ClinicalTrials.gov ID
- NCT04619862
- Acronym / sponsor ID
- H20-02023
- Conditions
- Pain, Neuropathic Pain, Irritability
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Child-Bright Network, BC Children's Hospital Research Institute
- Study start
- 15 May 2021 (actual)
- Primary completion
- 31 Mar 2026 (estimated)
- Study completion
- 30 Apr 2026 (estimated)
- First posted
- 6 Nov 2020 (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 rationale of this trial is to identify the clinical effect size of gabapentin in reducing and resolving pain in children with developmental brain disorders, specifically those with severe neurological impairment (SNI).
Detailed description
Background
Children with SNI may experience nociceptive-inflammatory pain as a result of their specific medical condition or procedures. Often, however, it is not clear what underlies the pain behavior as there is no clear inciting noxious event. The investigators define this entity of pain without an obvious source as Pain and Irritability of Unknown Origin (PIUO).
The investigators' work to date has developed an efficient, focused clinical pathway to evaluate children with SNI for all potential sources of nociceptive-inflammatory pain. Using this approach the "unknown" element of pain in these children is reduced and a source of PIUO may be found in individual cases, increasing the potential for treatment. Nevertheless there are children, who at the end of a thorough evaluation guided by a clinical pathway, will still have PIUO. These children may benefit from adjuvant analgesics such as gabapentin.
The evidence base supporting the use of gabapentin for pain and irritability in infants and children with neurological impairment rests on case series publications describing a limited number of retrospective cases. The lack of prospective, randomized studies, even for this commonly used medication, underpins the rationale for this trial.
Objectives
The primary objective of the pilot trial is to evaluate the clinically significant difference of gabapentin to decrease pain and irritability in children with SNI, when the source of pain and irritability is attributed to neurological dysregulation (nociplastic pain), as measured by parent-reported pain scores.
The investigators will compare the gabapentin versus placebo along an escalating dose range for both individual subjects and for the group. The investigators will aggregate the results of the completed N-of-1 trials across all subjects to estimate the group level comparative effectiveness of gabapentin in reducing pain and irritability.
Outcomes from this study will help with designing larger randomized control trials, especially with sample size and power calculations. It will also provide prospective information on drug effect.
Trial Design
This trial uses a single randomized multiple-measures cross-over design (N-of-1), with results aggregated over several subjects. This design is well-suited to outcomes that are highly specific to each individual and not amenable to precise measurement across a large cohort. The heterogenous nature of pain and irritability responses in children are more likely to be personally specific and characteristic, rather than generalizable.
Subjects will switch between gabapentin (G) and placebo (P) in a randomized order. The sequence of whether G precedes P (GP) or P precedes G (PG) will be randomized by the study pharmacist, and neither the clinician nor the subject (parent/caregiver) will know the sequence. Each subject will serve as their own control and experiment, allowing for a finer assessment of the treatment efficacy within each patient.
The primary variable assessed is the child's pain score. Pain and irritability will be measured using the Non-Communicating Children's Pain Checklist - Revised (NCCPC-R) at specified intervals throughout the randomized sequence of G : P. Additional measures of parent/caregiver burden and impact on their daily function will be undertaken weekly with the PROMIS-57, a tool adapted to measure the impact of the child's pain and irritability on parental functioning. Other measures will be of usual, known side effects (e.g., sedation) and of any unexpected adverse events.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- This trial uses a single randomized multiple-measures cross-over design (N-of-1), with results aggregated over several subjects. In the trial, each patient will switch between gabapentin (G) and placebo (P). The sequence of whether G precedes P (GP) or P precedes G (PG) will be randomized and neither the clinician nor the subject (parent/caregiver) will know the sequence. Each subject will serve as their own control and experiment, allowing for a finer assessment of the treatment efficacy within each patient.
| Arm | Type | Receives |
|---|---|---|
| Medication | Experimental | Drug: GabapentinGabapentin is clinically started at a low dose and titrated to clinical effect or maximum target dose, whichever is lower. The starting dose of gabapentin will be 5 mg/kg administered as oral liquid or via gastric or jejunal routes. On Day 1 of the study, the gabapentin will be administered once at bedtime and then increased according to a preset schedule. The dose will be increased every 3rd - 4th day in a step wise fashion of 13% - 50%, starting with the evening dose in order to accommodate sedation. The maximum dose for subjects will be as follows: < 15 kg to 60 mg/kg day and ≥15 kg to 45 mg/kg/day. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants on this arm receive placebo, masked and dispensed according to the same preset schedule as the Medication arm. |
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 as well as Communication Function Classification System (CFCS) level 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".
- The will be evidence of a comprehensive evaluation of PIUO in the child's medical history, showing no evidence for treatable sources (nociceptive-inflammatory) of pain and/or irritability symptoms.
Key exclusion criteria (13 listed)
- Children not within the specified age range
- Children with communication capabilities and cognitive development to localize their pain.
- Participants whose pain and or irritability is diagnosed through completion of the PIUO Pathway during the enrollment phase of the trial.
- Patients with a known hypersensitivity/allergy to the study medication
- Patients who are actively participating in another experimental therapy study for pain and/or irritability.
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 |
|---|---|---|
| GabapentinSee arm descriptions | Drug | Medication |
| PlaceboSee arm descriptions | Drug | Placebo |
Primary outcome
Mean pain and irritability score
Time frame: Days 11-19
The mean pain and irritability score on the Non-Communicating Children's Pain Checklist Revised (NCCPC-R) on active drug compared to placebo.
4 secondary outcomes
Identification of lowest effective dose
Time frame: Days 11-19 on active drug
Maximal effect dosage
Time frame: Days 11-19 on active drug
Identification of latency time
Time frame: Days 0-19
Adverse Events collection
Time frame: Through Sequence 1 and 2, total of 55 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
- Optimizing the Management of Pain and Irritability in Children with Severe Neurological ImpairmentLink 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 Phase 2 study testing Gabapentin 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 13 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: status not confirmed, 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anne-Mette Hermansen, MA (604 875 2000 ext. 6909, ahermansen@bcchr.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean pain and irritability score (time frame: Days 11-19). 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 8 May 2024.