Pregabalin Treatment for RDEB Pain and Itch

NCT03928093 | Completed Phase 3 DMC

• 1 other identifier: 1000060628
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Recessive dystrophic epidermolysis bullosa (RDEB) patients' quality of life is severely affected by neuropathic pain and itch, which have recently been demonstrated to be secondary to skin small fiber neuropathy. To date, there is no evidence on what the best agent is to control these symptoms. Based on the anecdotal data and safety profile, the investigators believe that pregabalin is a therapeutic agent that will be effective and safe in this population. The investigators propose to conduct a blinded study, using pregabalin versus placebo in which each patient serves as its own control (cross-over design). This is a feasibility study that will provide preliminary data on efficacy and safety of pregabalin in RDEB patients with neuropathic pain and itch and gather much needed data (dosage, titration schedule, outcome measures, etc) to inform the design of a larger cohort, controlled, multicenter trial.

Conditions

Pain, Neuropathic; Itch; Epidermolysis Bullosa

Outcome Measures

Primary Outcomes (1)

• Difference in the mean pain scores between pregabalin and placebo group: VAS

  It will be measured as difference in the mean pain values pre- and post-intervention for each group using the Visual Analog Scale (VAS).It is a 10 cm line with anchor statements on the left (no pain) and on the right (worst pain ever). The patient is asked to mark their pain level on the line.The pain is scored using the VAS by measuring the distance in centimeters (0-10) from the "no pain" anchoring point.

  12 weeks

Secondary Outcomes (8)

• Proportion of patients on pregabalin achieving a ≥75% reduction in their mean pain intensity score across last 7 days of treatment compared to baseline/wash-out

  12 weeks

• Proportion of patients on pregabalin achieving a ≥50% reduction in their mean pain intensity score across last 7 days of treatment compared to baseline/wash-out

  12 weeks

• Difference in the average pain score assessed using VAS between first and second treatment periods (period effect)

  24 weeks

• Proportion of patients on pregabalin achieving a ≥75% reduction in their mean itch intensity score across last 7 days of treatment compared to baseline/wash-out

  24 weeks

• Proportion of patients on pregabalin achieving a ≥50% reduction in their mean itch intensity score across last 7 days of treatment compared to baseline/wash-out

  12 weerks

Other Outcomes (6)

• Correlation between pain score (as measured by VAS), iscorEB patient portion score and QOLEB (for patients over 18 yrs) total scores.

  24 weeks

• Correlation between pain score( as measured by VAS) and iscorEB clinician portion score and Epidermolysis Bullosa Disease Activity and Scarring Index(EBDASI) score.

  24 weeks

• Proportion of patients experiencing adverse events, minor, severe and serious (life-threatening)

  24 weeks

Study Arms (2)

Pregabalin followed by placebo

EXPERIMENTAL

The study has a crossover design. Participants in this arm will receive pregabalin during the first study treatment period for ten weeks and placebo during their second ten-week treatment period . The dose will depend on the participant's weight and phase of treatment period. Each treatment period consists of 4 weeks of escalating dose until the desired maximum , 4 weeks of active treatment and 2 weeks of titrating down.

Drug: Pregabalin

Placebo followed by Pregabalin

EXPERIMENTAL

Participants will receive placebo during the first treatment period of the study(10 weeks) followed by 10 weeks of pregabalin treatment . The dose will depend on the participant's weight and phase of the treatment period . Each treatment period consists of 3 phases: 4 weeks of escalating dose until the desired maximum, 4 weeks of active treatment and 2 weeks of titrating down.

Drug: Pregabalin

Interventions

Pregabalin DRUG

Pregabalin /placebo capsules will be taken by mouth and will be prescribed for the study participants in the doses, depending on their weight and treatment phase: Participant \< 25 kg at baseline will start with 50 mg per day, increasing the dose by 50 mg each week until their maximum dose 200 mg per day; Participants who are greater than or equal to 25 kg at baseline will start with 100 mg per day, increasing their dose by 50 mg each week until their target dose 300 mg per day is achieved. The study medication will be taken twice per day.The dose will be weaned down every 1-2 days by 25 mg in the last two weeks of each treatment period.

Also known as: Placebo

Placebo followed by Pregabalin; Pregabalin followed by placebo

Eligibility Criteria

• Age: 8 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: \> 8 - 40 years (we selected this range due to lack of data in younger population and the difficulty in getting patient reported outcomes in younger patients)
• Diagnosis of RDEB (by a dermatologist and/or EB specialist and/or genetic confirmation)
• Evidence of neuropathy defined by: thermal sensory loss (determined by a thermal roller, ROLLTEMP2, Sometic, Sweden) 14 and \> 4/10 score using a screening tool for neuropathic pain, the DN4 questionnaire 15
• Pain intensity of \> 4/10 on a 0-10 VAS scale measured daily (reduced frequency is also acceptable) at night over 2 weeks
• Itch intensity of \> 4/10 on a 0-10 VAS scale measures daily (reduced frequency is also acceptable) at night over 2 weeks
• Consent to follow with study procedures

You may not qualify if:

• Intolerance and/or allergy to Pregabalin or gabapentin
• Lactose intolerance (placebo capsules contain lactose)
• Pregabalin use within 2 weeks before study enrolment
• Ongoing treatment with gabapentin, amitriptyline, duloxetine, nortriptyline, other tricyclics or SNRIs
• Medical conditions that would be considered as contraindications for pregabalin treatment (ischemic heart disease, cardiac dysrhythmia, glaucoma, history of urinary retention)
• Pregnancy
• History of use of restrictive substances or alcohol abuse
• Allergy to gelatin

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Epidemolysis Bullosa Research Partnership: collaborator

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

Related Publications (1)

• Calvo M, Tejos-Bravo M, Passi-Solar A, Espinoza F, Fuentes I, Lara-Corrales I, Pope E. Pregabalin for Neuropathic Pain and Itch in Recessive Dystrophic Epidermolysis Bullosa: A Randomized Crossover Trial. JAMA Dermatol. 2024 Dec 1;160(12):1314-1319. doi: 10.1001/jamadermatol.2024.3767.

  PMID: 39441591 DERIVED

MeSH Terms

Conditions

Neuralgia; Pruritus; Epidermolysis Bullosa

Interventions

Pregabalin

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases, Vesiculobullous

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All investigators, assessors and participants will be blinded to the intervention. The randomization will be done by the research pharmacist. Unblinding before the study completion is allowed only in case of serious adverse events.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dermatology section head

Model Details: there two treatment periods in the study. All of the study participants will receive pregabalin treatment during one of these two 10-week treatment periods, and placebo - during the other one.

Study Record Dates

• First Submitted: March 27, 2019
• First Posted: April 25, 2019
• Study Start: August 7, 2019
• Primary Completion: March 1, 2023
• Study Completion: February 1, 2024
• Last Updated: January 22, 2025

Record last verified: 2025-01

Locations

CA (1)