Pregabalin Treatment for RDEB Pain and Itch

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Brief Title

Pregabalin Treatment for RDEB Pain and Itch

Official Title

A Double-blind, Randomized, Cross-over, Feasibility Trial of Pregabalin for the Treatment of Recessive Dystrophic Epidermolysis Bullosa-associated Neuropathic Pain and Itch

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.
    

Detailed Description

      Neuropathic pain and itch are significant symptoms that affect RDEB patients' quality of
      life. To date, there is no evidence on what the best agent is to control these symptoms.

      Based on the anecdotal data and the safety profile, the investigator believes that pregabalin
      is a therapeutic agent that will be effective and safe in this population.

      This is a pilot, randomized, double-blinded, cross-over trial of pregabalin vs placebo for
      the treatment of RDEB associated neuropathic pain and itch. The study will run for 24 weeks
      and will have 4 separate phases with 6 overall visits: 1. Observation/wash out period (2
      weeks); 2. ARM-1, ½ of the patients will receive pregabalin(A) and ½ the placebo (B) (10
      weeks); 3. Wash out period (2 weeks) and 4. ARM-2 (patients who received placebo will receive
      pregabalin and pregabalin will receive placebo (10 weeks).

      Patients will be recruited during the regular clinic visits or invited to participate via a
      letter followed by 2 phone calls.

        1. Screening/Wash out period #1 (Visit 0)to assess eligibility criteria and the background
           pain and itch level (2 weeks), as well as the effectiveness of patients' "standard
           pain/itch interventions". Throughout this phase and the rest of the study, patients will
           receive pain and itch medications, except those that interfere with the pregabalin (see
           exclusion criteria).

             -  Investigators will assess the eligibility criteria, including having moderate to
                severe pain (>4/10), the evidence of neuropathy using a thermal roller device
                ROLLTEMP2, Sometic, and a screening tool for neuropathic pain, the DN4
                questionnaire 15 (Appendix 2).

             -  Investigators will collect basic demographic data, medication information and
                disease severity using iscorEB clinician portion, a valid outcome measure that
                evaluates the disease severity 16 and EBDASI 17 ( Data collection form:
                Baseline/Screening Form)

             -  Patients will be asked to report on their disease severity using iscorEB patient
                portion (all ages) that includes pain and itch domains and QOLEB 18 for those over
                18 years of age (validated only for the adult population).

             -  Patients will be instructed how to collect daily assessments of pain and itching
                for 14 days before the next visit. For the overall pain intensity assessment, the
                investigators will use a 100mm VAS, where 0 is no pain and 10- the worst pain ever
                experienced. For itch assessments, the investigators will ask patients to score
                each day, before going to bed, the degree of itching experienced that day using a
                100 mm horizontal VAS where 0 is no itch and 10 is the worst itch.19 The
                investigators chose the single item for its reliability, validity and
                responsiveness to change. These values will represent patient's baseline pain
                (AvePain-00) and itch (AveItch-00).

        2. ARM1 intervention study period (Visits 1 & 2): ½ of the patients will receive the active
           intervention (Pregabalin) and ½ the placebo. This phase will be of 10 weeks duration and
           will consist of 4 weeks of escalating dose until the desired maximum, 4 weeks of active
           treatment and 2 weeks of titration down (see titration schedule in the Appendix
           1)Patients will receive either active intervention (pregabalin) or placebo including
           instruction of how to administer them.

           Visit 1: (Week 2)

             -  Investigator will collect the data on pain and itching from the 2 weeks wash-out
                and will determine the average pain and itching of approximately 14 days prior to
                the study visit 1(AvePain-00, AveItch-00)

             -  Patients will be asked to report on their disease severity using iscorEB patient
                portion and QOLEB for those over 18 years of age.

             -  A team member will call patient twice a week during the escalation phase to inquire
                about adverse events

             -  Patients will be instructed to collect daily assessments of pain, and itch for 7
                days before next visit (~from weeks 9-10).

           Visit 2: (Week 10)

             -  Patients will be instructed to contact investigator if experiencing any adverse
                events.

             -  Investigator will collect the data on pain and itching from approximately 7 days
                prior to visit 2 (~weeks 9-10) and will determine the average pain and itching
                (AvePain-02, AveItch-02)

             -  Patients will be asked to report on their disease severity using iscorEB patient
                portion and QOLEB for those over 18 years of age.

             -  Adverse events (see potential risks, DCF follow up, patient's diary)

             -  Patients will be instructed to collect daily assessments of pain, and itch for 7
                days before next visit (~from weeks 13-14)

        3. Wash out period #2 (2 weeks) Visit 3 (Week 14)

             -  Investigator will collect the data on pain and itching and will determine the
                average pain and itching of approximately 7 days prior to the study visit 3
                (AvePain-03, AveItch-03)

             -  Patients will be asked to report on their disease severity using iscorEB patient
                portion and QOLEB for those over 18 years of age.

             -  Investigator will collect adverse events (see potential risks, DCF follow up,
                patient's diary)

             -  Patients will be instructed to collect daily assessments of pain, and itch for 7
                days before next visit (~from weeks 21-22)

             -  All study procedures at visit 3 will be similar to visit 1.

        4. ARM2 intervention study period (Visits 4 & 5 (Week 22 and 24): patients randomized to
           placebo will receive pregabalin and those on placebo will get the pregabalin conducted
           similarly as in ARM1

             -  All study procedures at visit 4 will be similar to visit 2

             -  The outcome measures will be similar, but will be recorded as (AvePain-04,
                AveItch-04)

             -  Weaning will be similar to ARM1

             -  End of the Study visit: Visit 5 (Week 24) The outcome measures will be similar, but
                will be recorded as AvePain-05, AveItch-05)
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

 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

Condition

Pain, Neuropathic

Intervention

Pregabalin

Study Arms / Comparison Groups

 Pregabalin followed by placebo
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

15

Start Date

August 7, 2019

Completion Date

June 30, 2023

Primary Completion Date

December 1, 2022

Eligibility Criteria

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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
      

Gender

All

Ages

8 Years - 40 Years

Accepts Healthy Volunteers

No

Contacts

, 416-813-8185, [email protected]

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT03928093

Organization ID

1000060628


Responsible Party

Principal Investigator

Study Sponsor

The Hospital for Sick Children

Collaborators

 Epidemolysis Bullosa Research Partnership

Study Sponsor

, , 


Verification Date

June 2021