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Pregabalin Treatment for RDEB Pain and Itch

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ClinicalTrials.gov Identifier: NCT03928093
Recruitment Status : Recruiting
First Posted : April 25, 2019
Last Update Posted : August 20, 2019
Sponsor:
Collaborator:
Epidemolysis Bullosa Research Partnership
Information provided by (Responsible Party):
Elena Pope, The Hospital for Sick Children

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.

Condition or disease Intervention/treatment Phase
Pain, Neuropathic Itch Epidermolysis Bullosa Drug: Pregabalin Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: 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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
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
Actual Study Start Date : August 7, 2019
Estimated Primary Completion Date : May 1, 2021
Estimated Study Completion Date : June 30, 2021


Arm Intervention/treatment
Experimental: Pregabalin followed by placebo
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
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.
Other Name: Placebo

Experimental: Placebo followed by Pregabalin
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
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.
Other Name: Placebo




Primary Outcome Measures :
  1. Difference in the mean pain scores between pregabalin and placebo group: VAS [ Time Frame: 12 weeks ]
    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.


Secondary Outcome Measures :
  1. 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 [ Time Frame: 12 weeks ]
    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

  2. 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 [ Time Frame: 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

  3. Difference in the average pain score assessed using VAS between first and second treatment periods (period effect) [ Time Frame: 24 weeks ]
    Difference in the average pain score assessed using VAS, reported by the patient between first and second treatment periods. Visual Analog Scale (VAS) is a 10 cm line with anchor statements on the left (0 -no pain) and on the right (10- 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.

  4. 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 [ Time Frame: 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.The intensity of itch is measured using the Visual Analog Scale for itch(VAS).It is a 10 cm line with anchor statements on the left (no itching) and on the right (worst possible itching). The patient is asked to mark the intensity of itch on the line. The itch is scored using the VAS by measuring the distance in centimeters (0-10)from the "no itch" anchoring point.

  5. 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 [ Time Frame: 12 weerks ]
    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

  6. Difference in the average itch score as assessed using VAS between the first and the second treatment periods (period effect). [ Time Frame: 24 weeks ]
    Difference in the average itch score as assessed using VAS( reported by the patient) between the first and the second treatment periods (period effect). The intensity of itch is measured using the Visual Analog Scale for itch (VAS).It is a 10 cm line with anchor statements on the left (0- no itching) and on the right (10 -worst possible itching). The patient is asked to mark the intensity of itch on the line. The itch is scored using the VAS by measuring the distance in centimeters (0-10) from the "no itch" anchoring point.

  7. Changes in the Quality of Life in Epidermolysis Bullosa Questionnaire score(QOLEB) for patients >18yrs in the intervention versus placebo [ Time Frame: 24 weeks ]

    Changes in the QOLEB for patients >18yrs in the intervention versus placebo. QOLEB is a measurement tool containing 17questions.Each question has a score range from 0-3.Total score range is between 0 and 51.

    iscorEB is a measurement tool for evaluating the disease severity in EB patient.It evaluates the cutaneous,mucosal and other organ impact of EB and includes clinician and patient reported outcomes in a single instrument. Score ranges between 0-120 for both reported outcomes.


  8. Changes in iscorEB (instrument for scoring clinical outcomes for research of EB), patient portion score in the intervention versus placebo [ Time Frame: 24 weeks ]
    iscorEB is a measurement tool for evaluating the disease severity in EB patient. It evaluates the cutaneous, mucosal and other organ impact of EB and includes clinician and patient reported outcomes in a single instrument. Score ranges between 0-120 for both reported outcomes. Patient portion of this instrument contains 15 questions. Each question has a score range from 0-8.Total score range for iscorEB patient portion is between 0 and 120. Reduction in iscorEB scores indicates improvement. An increase in score indicates deterioration.


Other Outcome Measures:
  1. Correlation between pain score (as measured by VAS), iscorEB patient portion score and QOLEB (for patients over 18 yrs) total scores. [ Time Frame: 24 weeks ]
    Correlation between pain score, as measured by Visual Analog Scale (VAS), iscorEB (instrument for scoring clinical outcomes for research of EB)- patient portion score, and Quality of Life in Epidermolysis Bullosa Questionnaire (QOLEB) score (for patients over 18 years). Please see full description of the mentioned instruments above.

  2. Correlation between pain score( as measured by VAS) and iscorEB clinician portion score and Epidermolysis Bullosa Disease Activity and Scarring Index(EBDASI) score. [ Time Frame: 24 weeks ]
    Correlation between pain score(as measured by Visual Analog Scale), iscorEB (instrument for scoring clinical outcomes for research of EB)- clinician portion score and EBDASI total score.Total EBDASI score ranges of 0-42, 43-106 and 107-506 corresponded to mild, moderate and severe disease respectively. Reduction in EBDASI activity scores of greater than 9 indicated clinically significant improvement. An increase of 3 in the activity score indicated deterioration. iscorEB is a measurement tool for evaluating the disease severity in EB patient. It evaluates the cutaneous, mucosal and other organ impact of EB and includes clinician and patient reported outcomes in a single instrument. Clinician score ranges between 0-120 between. Reduction in iscorEB scores indicates improvement. An increase in score indicates deterioration.

  3. Proportion of patients experiencing adverse events, minor, severe and serious (life-threatening) [ Time Frame: 24 weeks ]
    Proportion of patients experiencing adverse events

  4. Proportion of patients that dropped out of the study as a result of an adverse event [ Time Frame: 24 weeks ]
    Proportion of patients that dropped out of the study as a result of an adverse event

  5. Correlation between itch score (as measured by VAS),iscorEB patient portion and QOLEB (for patients over 18 yrs) total scores. [ Time Frame: 24 weeks ]
    Correlation between itch score( as measured by VAS),iscorEB patient portion, and QOLEB (for patients over 18 yrs.) total scores.

  6. Correlation between itch score( as measured by VAS) and iscorEB clinician and Epidermolysis Bullosa Disease Activity and Scarring Index(EBDASI) [ Time Frame: 24 weeks ]
    Correlation between itch score(as measured by VAS) and iscorEB clinician and EBDASI total scores. Total EBDASI score ranges of 0-42, 43-106 and 107-506 corresponded to mild, moderate and severe disease respectively. Reduction in EBDASI activity scores of greater than 9 indicated clinically significant improvement. An increase of 3 in the activity score indicated deterioration.



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Ages Eligible for Study:   8 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03928093


Contacts
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Contact: Elena Pope, MD 416-813-8185 Elena.Pope@sickkids.ca
Contact: Hanna Fadzeyeva 416-813-7835 Hanna.Fadzeyeva@sickkids.ca

Locations
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Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G1X8
Contact: Elena Pope, MD    416-813-8185    Elena.Pope@sickkids.ca   
Contact: Hanna Fadzeyeva    416-813-7835    Hanna.Fadzeyeva@sickkids.ca   
Sponsors and Collaborators
The Hospital for Sick Children
Epidemolysis Bullosa Research Partnership

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Responsible Party: Elena Pope, Dermatology section head, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT03928093     History of Changes
Other Study ID Numbers: 1000060628
First Posted: April 25, 2019    Key Record Dates
Last Update Posted: August 20, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Neuralgia
Epidermolysis Bullosa
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Pain
Neurologic Manifestations
Signs and Symptoms
Pregabalin
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs