Efficacy of Gabapentin in Treating Pain in Children With SNI (Gabapentin Trial)

NCT04619862 | Recruiting Phase 2 DMC

• 1 other identifier: H20-02023
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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). 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).

Conditions

Pain; Neuropathic Pain; Irritability

Outcome Measures

Primary Outcomes (1)

• 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.

  Days 11-19

Secondary Outcomes (4)

• Identification of lowest effective dose

  Days 11-19 on active drug

• Maximal effect dosage

  Days 11-19 on active drug

• Identification of latency time

  Days 0-19

• Adverse Events collection

  Through Sequence 1 and 2, total of 55 days

Other Outcomes (1)

• Improvement in parent fatigue levels

  Day 1 of Sequence 1 and 2 (each Sequence is 26 days with a 3 day washout period in between) and Study End, day 55

Study Arms (2)

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.

Drug: Gabapentin

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Gabapentin DRUG

See arm descriptions

Medication

Placebo DRUG

See arm descriptions

Placebo

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• University of British Columbia: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Child-Bright Network: collaborator
• BC Children's Hospital Research Institute: collaborator

Study Sites (1)

BC Children's Hospital

Vancouver, British Columbia, V6H 3N1, Canada

RECRUITING

Related Links

• Optimizing the Management of Pain and Irritability in Children with Severe Neurological Impairment

MeSH Terms

Conditions

Pain; Neuralgia

Interventions

Gabapentin

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Hal Siden, MD

  BC Children's Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne-Mette Hermansen, MA

CONTACT

604 875 2000; ahermansen@bcchr.ca

Gail Andrews, RN

CONTACT

604 875 2000; gandrews@cw.bc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Both active drug and placebo will be masked in a liquid formulation, and administered via the same route (oral, direct gastric route, or direct jejunal route) depending on the subject's usual feeding approach. The label applied to the bottle will be blinded and identical flavouring will be added to the drug and placebo for additional masking.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: October 27, 2020
• First Posted: November 6, 2020
• Study Start: May 15, 2021
• Primary Completion: March 31, 2026
• Study Completion: April 30, 2026
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)