Gabapentin for Neuropathic Pain in Children

Overseen By Anne-Mette Hermansen, MA

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of British Columbia

Disqualifiers: Renal disease, Hepatic impairment, Sickle cell, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 26 days per sequence

5 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications. It's best to discuss this with the trial coordinators or your doctor.

What evidence supports the effectiveness of the drug gabapentin for treating neuropathic pain in children?

Gabapentin has been shown to help reduce neuropathic pain in children, as seen in a report where five adolescents experienced significant pain relief with minimal side effects. Additionally, a case study highlighted a 12-year-old boy whose severe pain improved significantly after using gabapentin. ^{1 2 3 4 5}

Is gabapentin safe for treating neuropathic pain in children?

Gabapentin has been used to treat neuropathic pain in children with minimal side effects reported in some cases, but its safety and effectiveness are not fully established, and more research is needed. ^{1 2 4 6 7}

How is the drug gabapentin unique for treating neuropathic pain in children?

Gabapentin is unique because it is originally an antiepileptic drug that has shown effectiveness in reducing neuropathic pain in children with minimal side effects, even though its use for this purpose is off-label (not officially approved). It can be used as an add-on to morphine for severe pain and is being studied in a new liquid form for easier administration in children. ^{1 2 4 5 6}

Research Team

Hal Siden, MD

Principal Investigator

BC Children's Hospital Research Institute

Eligibility Criteria

This trial is for children aged 6 months to 18 years with severe neurological impairment who experience unexplained pain and irritability. They must have significant communication or cognitive disabilities, scoring high on specific scales indicating persistent distress without an obvious cause.

Inclusion Criteria

My child, aged 6 months to 18 years, has severe neurological issues and unexplained pain or irritability.

My child's medical history shows they've been fully checked for treatable pain causes.

My child has severe cognitive or communication issues and significant physical limitations.

Exclusion Criteria

My kidney function is reduced with a filtration rate below 60 mL/min.

My child can point to or tell where it hurts.

I have been diagnosed with pain and irritability.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gabapentin or placebo in a randomized cross-over design, with dose titration every 3-4 days

26 days per sequence

Weekly assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Gabapentin
• Placebo

Trial Overview The trial tests the effectiveness of Gabapentin in alleviating pain compared to a placebo in children with severe brain-based developmental disabilities. It aims to determine how well Gabapentin can reduce or resolve their pain and irritability.

Participant Groups

Group I: Medication Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

Participants on this arm receive placebo, masked and dispensed according to the same preset schedule as the Medication arm.

Gabapentin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Neurontin for:

• Postherpetic neuralgia
• Partial-onset seizures

Approved in European Union as Gabapentin for:

• Peripheral neuropathic pain
• Partial-onset seizures

Approved in Canada as Gabapentin for:

• Postherpetic neuralgia
• Partial-onset seizures

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

BC Children's Hospital Research Institute

Collaborator

Trials

14

Recruited

2,800+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Child-Bright Network

Collaborator

Trials

4

Recruited

970+

Findings from Research

The GAPP-2 study is a randomized, double-blind, placebo-controlled trial involving 66 children aged 3 months to 18 years, aimed at evaluating the efficacy and safety of gabapentin as an add-on to morphine for treating severe chronic neuropathic or mixed pain over a 12-week period.

The primary goal is to determine if gabapentin can significantly reduce pain scores compared to placebo, potentially leading to better pain management strategies for children, while also confirming the appropriate pediatric dosing for gabapentin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gabapentin as add-on to morphine for severe neuropathic or mixed pain in children from age 3 months to 18 years - evaluation of the safety, pharmacokinetics, and efficacy of a new gabapentin liquid formulation: study protocol for a randomized controlled trial. de Leeuw, TG., Mangiarini, L., Lundin, R., et al.[2020]

Gabapentin, an antiepileptic drug, showed rapid analgesic effects in treating neuropathic pain in children, with pain scores improving significantly within one week (from 9 or 10 to 4 or 3) in a small study of five patients.

The treatment was well-tolerated with minimal adverse effects, suggesting that gabapentin should be considered earlier in the management of neuropathic pain in adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with gabapentin for neuropathic pain in adolescents: report of five cases. Butkovic, D., Toljan, S., Mihovilovic-Novak, B.[2018]

Gabapentin was effective in treating severe neuropathic pain in a 12-year-old male patient, which had previously hindered his rehabilitation after sciatic nerve damage from a firearm injury.

This case highlights the potential of gabapentin as a treatment option for pediatric patients with neuropathic pain, especially when other medical treatments have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gabapentin Treatment for Neuropathic Pain in a Child with Sciatic Nerve Injury. Akkurt, HE., Gümüş, H., Göksu, H., et al.[2020]

The GABA-1 trial is a multicenter study involving 94 participants aged 3 months to under 18 years, comparing the efficacy and safety of gabapentin to tramadol for treating chronic neuropathic or mixed pain over a period of 16-19 weeks.

The primary goal is to evaluate pain relief effectiveness by measuring average pain scores after 15 weeks, while also assessing safety and quality of life, which will help establish optimal dosing for gabapentin in the pediatric population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-inferiority double-blind randomised controlled trial comparing gabapentin versus tramadol for the treatment of chronic neuropathic or mixed pain in children and adolescents: the GABA-1 trial-a study protocol. Kaguelidou, F., Le Roux, E., Mangiarini, L., et al.[2020]

A survey of 117 practitioners revealed that there is no consensus on the diagnostic process for chronic neuropathic pain in children, with most relying on physical exams and patient history.

First-choice treatments for moderate neuropathic pain included gabapentin, amitriptyline, and pregabalin, while treatments for moderate mixed pain varied widely, highlighting the need for standardized diagnostic tools and treatment protocols for pediatric pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and Treatment of Chronic Neuropathic and Mixed Pain in Children and Adolescents: Results of a Survey Study amongst Practitioners. de Leeuw, TG., der Zanden, TV., Ravera, S., et al.[2020]

Gabapentin effectively reduced neuropathic pain in a child suffering from mercury poisoning, indicating its potential as a treatment option for similar cases.

The treatment was well tolerated, with no severe side effects reported, suggesting that gabapentin is a safe analgesic for children with neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Gabapentin for neurophatic pain in children: a case report]. Dayioğlu, M., Tuncer, S., Reisli, R.[2018]

Gabapentin, commonly prescribed for neuropathic pain, lacks sufficient evidence for its safety and efficacy, as many trial results, particularly regarding its harms, have not been fully reported.

This study aims to analyze and disclose adverse events from six previously unreported trials of gabapentin, using clinical study reports and individual participant data to provide a clearer understanding of its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restoring invisible and abandoned trials of gabapentin for neuropathic pain: a clinical and methodological investigation. Mayo-Wilson, E., Chen, X., Qureshi, R., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Gabapentin as add-on to morphine for severe neuropathic or mixed pain in children from age 3 months to 18 years - evaluation of the safety, pharmacokinetics, and efficacy of a new gabapentin liquid formulation: study protocol for a randomized controlled trial. [2020]

2. France pubmed.ncbi.nlm.nih.gov

Experience with gabapentin for neuropathic pain in adolescents: report of five cases. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Gabapentin Treatment for Neuropathic Pain in a Child with Sciatic Nerve Injury. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Non-inferiority double-blind randomised controlled trial comparing gabapentin versus tramadol for the treatment of chronic neuropathic or mixed pain in children and adolescents: the GABA-1 trial-a study protocol. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Diagnosis and Treatment of Chronic Neuropathic and Mixed Pain in Children and Adolescents: Results of a Survey Study amongst Practitioners. [2020]

6. Turkey pubmed.ncbi.nlm.nih.gov

[Gabapentin for neurophatic pain in children: a case report]. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Restoring invisible and abandoned trials of gabapentin for neuropathic pain: a clinical and methodological investigation. [2022]