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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether gabapentin (also known as Neurontin) can reduce pain and irritability in children with severe brain-based developmental disabilities. It focuses on children who cannot easily express where or why they are in pain, a condition known as Pain and Irritability of Unknown Origin (PIUO). Participants will receive either gabapentin or a placebo to evaluate the medication's effectiveness. Children who may be suitable often have severe disabilities and cannot clearly communicate their pain. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

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.

Is there any evidence suggesting that gabapentin is likely to be safe for children with severe neurological impairment?

A previous study administered gabapentin to children for pain relief, and 76% reported feeling less pain. However, 42% experienced possible side effects. Gabapentin is not officially approved by major health agencies for treating pain in children, indicating that doctors are still learning about its safety for this use.

While gabapentin is generally considered safe for adults, limited information exists about its safety in children with nerve-related pain. Research so far suggests it can help reduce pain, but side effects might occur. Monitoring for any changes is important if considering gabapentin for pain relief. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for neuropathic pain?

Gabapentin is unique because it's being explored for neuropathic pain in children, a condition with limited specific treatments available for this age group. Unlike standard pain relief options that often involve medications like opioids or nonsteroidal anti-inflammatory drugs (NSAIDs), gabapentin works by calming overactive nerves and reducing pain signals in the brain. Researchers are excited about gabapentin because it offers a non-opioid option, potentially leading to fewer side effects and dependency issues. Additionally, its flexible dosing, starting at a low level and adjusted to achieve the best effect, provides a tailored approach to managing pain safely in children.

What evidence suggests that gabapentin might be an effective treatment for pain and irritability of unknown origin in children with severe neurological impairment?

Research has shown that gabapentin, which participants in this trial may receive, can help manage nerve pain, especially in children with developmental disabilities. Other studies have found that gabapentin safely lowers pain levels without causing unexpected side effects. It has successfully treated pain in children and teens who have undergone limb amputations or certain surgeries. Gabapentin has also proven beneficial in pediatric palliative care, significantly reducing pain. These findings suggest that gabapentin could help reduce pain and irritability in children with severe neurological issues. ^{1 3 5 6 7}

Who Is on the Research Team?

Hal Siden, MD

Principal Investigator

BC Children's Hospital Research Institute

Are You a Good Fit for This Trial?

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'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.

My child often feels pain for no clear reason and it's very distressing.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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, 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, 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10716891/

The Pharmacological Treatment of Neuropathic Pain in Children In rodent models of neuropathic pain, gabapentin has shown to have anti-allodynic effects and an attenuation of neuropathic pain behaviors [58].

2. publications.aap.org publications.aap.org/hospitalpediatrics/article/14/1/e57/196219/Safety-and-Efficacy-of-Gabapentin-for-Pain-in

Safety and Efficacy of Gabapentin for Pain in Pediatric ... Ultimately, gabapentin was used safely to treat neuropathic pain in children and adolescents with limb amputation and limb-sparing procedures ...

3. jpsmjournal.com jpsmjournal.com/article/S0885-3924(23)00784-4/fulltext

Gabapentin for Pain in Pediatric Palliative Care The overall outcomes suggest gabapentin was beneficial in reducing pain intensity without causing an unexpected level of AEs in this vulnerable ...

4. research.childrenshospital.org research.childrenshospital.org/research-units/berde-lab-research/ongoing-research/evaluating-clinical-effectiveness-gabapentin-and

Evaluating the Clinical Effectiveness of Gabapentin and ... Both Gabapentin and Oxcarbazepine will result in significant reduction in pain scores when compared to each patient's baseline. Patients who continue on active ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/62/NCT04619862/Prot_000.pdf

Efficacy of Gabapentin in Treating Pain in Children with ... The primary objective of the trial is to evaluate the effectiveness of gabapentin to decrease pain and irritability in children with SNI, when ...

6. mypcnow.org mypcnow.org/fast-fact/gabapentin-for-neuropathic-pain/

Gabapentin for Neuropathic Pain Pediatric use: There is limited data available assessing its effectiveness in neuropathic pain in children. The American Pain Society ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/020235s064_020882s047_021129s046lbl.pdf

NEURONTIN (gabapentin) - accessdata.fda.gov Safety and effectiveness of NEURONTIN in the management of postherpetic neuralgia in pediatric patients have not been established. Safety and effectiveness as ...