Treatment of Chronic Itch in Atopic Dermatitis With Topical Naltrexone

NCT04154033 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: DERM-2019-27870
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

To study the etiology and the epigenetic pathways leading to and regulating chronic itch. Similarly, to examine the mechanisms underlying skin changes, including epigenetic alterations while also testing the efficacy of medications, especially topical intervention. In this study, the investigators aim to examine chronic sensory disorder mechanisms related to chronic itch.

Conditions

Atopic Dermatitis; Pruritus; Dermatitis

Outcome Measures

Primary Outcomes (13)

• Visual Analog Scale for Itching: Circadian 2 Hours AW

  To assess the effects of circadian rhythm on pruritus, participants will record itch intensity using a visual analog scale (VAS) at the following time points after waking (AW): AW+2h for 7 days. VAS ranges from 0mm (no itch) to 100mm (unbearable itch). The mean (in millimeters) of 7 daily measurements will be reported.

  7 days

• Visual Analog Scale for Itching: Circadian 4 Hours AW

  To assess the effects of circadian rhythm on pruritus, participants will record itch intensity using a visual analog scale (VAS) at the following time points after waking (AW): AW+4h for 7 days. VAS ranges from 0mm (no itch) to 100mm (unbearable itch). The mean (in millimeters) of 7 daily measurements will be reported.

  7 days

• Visual Analog Scale for Itching: Circadian 6 Hours AW

  To assess the effects of circadian rhythm on pruritus, participants will record itch intensity using a visual analog scale (VAS) at the following time points after waking (AW): AW+6h for 7 days. VAS ranges from 0mm (no itch) to 100mm (unbearable itch). The mean (in millimeters) of 7 daily measurements will be reported.

  7 days

• Visual Analog Scale for Itching: Circadian 8 Hours AW

  To assess the effects of circadian rhythm on pruritus, participants will record itch intensity using a visual analog scale (VAS) at the following time points after waking (AW): AW+8h for 7 days. VAS ranges from 0mm (no itch) to 100mm (unbearable itch). The mean (in millimeters) of 7 daily measurements will be reported.

  7 days

• Visual Analog Scale for Itching: Circadian 10 Hours AW

  To assess the effects of circadian rhythm on pruritus, participants will record itch intensity using a visual analog scale (VAS) at the following time points after waking (AW): AW+10h for 7 days. VAS ranges from 0mm (no itch) to 100mm (unbearable itch). The mean (in millimeters) of 7 daily measurements will be reported.

  7 days

• Visual Analog Scale for Itching: Circadian 12 Hours AW

  To assess the effects of circadian rhythm on pruritus, participants will record itch intensity using a visual analog scale (VAS) at the following time points after waking (AW): AW+12h for 7 days. VAS ranges from 0mm (no itch) to 100mm (unbearable itch). The mean (in millimeters) of 7 daily measurements will be reported.

  7 days

• Visual Analog Scale for Itching: Treatment 0 min

  To assess the effects of naltrexone 1% or placebo cream on pruritus, participants will record itch intensity using a visual analog scale (VAS) at 0 minutes after applying cream for 3 pruritis attacks in 1 week. VAS ranges from 0mm (no itch) to 100mm (unbearable itch). The mean (in millimeters) over 3 pruritis attacks will be reported.

  0 minutes after applying topical cream

• Visual Analog Scale for Itching: Treatment 20 min

  To assess the effects of naltrexone 1% or placebo cream on pruritus, participants will record itch intensity using a visual analog scale (VAS) at 20 minutes after applying cream for 3 pruritis attacks in 1 week. VAS ranges from 0mm (no itch) to 100mm (unbearable itch). The mean (in millimeters) over 3 pruritis attacks will be reported.

  20 minutes after applying topical cream

• Visual Analog Scale for Itching: Treatment 40 min

  To assess the effects of naltrexone 1% or placebo cream on pruritus, participants will record itch intensity using a visual analog scale (VAS) at 40 minutes after applying cream for 3 pruritis attacks in 1 week. VAS ranges from 0mm (no itch) to 100mm (unbearable itch). The mean (in millimeters) over 3 pruritis attacks will be reported.

  40 minutes after applying topical cream

• Visual Analog Scale for Itching: Treatment 1 Hour

  To assess the effects of naltrexone 1% or placebo cream on pruritus, participants will record itch intensity using a visual analog scale (VAS) at 1 hour after applying cream for 3 pruritis attacks in 1 week. VAS ranges from 0mm (no itch) to 100mm (unbearable itch). The mean (in millimeters) over 3 pruritis attacks will be reported.

  1 hour after applying topical cream

• Visual Analog Scale for Itching: Treatment 2 Hours

  To assess the effects of naltrexone 1% or placebo cream on pruritus, participants will record itch intensity using a visual analog scale (VAS) at 2 hours after applying cream for 3 pruritis attacks in 1 week. VAS ranges from 0mm (no itch) to 100mm (unbearable itch). The mean (in millimeters) over 3 pruritis attacks will be reported.

  2 hours after applying topical cream

• Visual Analog Scale for Itching: Treatment 3 Hours

  To assess the effects of naltrexone 1% or placebo cream on pruritus, participants will record itch intensity using a visual analog scale (VAS) at 3 hours after applying cream for 3 pruritis attacks in 1 week. VAS ranges from 0mm (no itch) to 100mm (unbearable itch). The mean (in millimeters) over 3 pruritis attacks will be reported.

  3 hours after applying topical cream

• Visual Analog Scale for Itching: Treatment 4 Hours

  To assess the effects of naltrexone 1% or placebo cream on pruritus, participants will record itch intensity using a visual analog scale (VAS) at 4 hours after applying cream for 3 pruritis attacks in 1 week. VAS ranges from 0mm (no itch) to 100mm (unbearable itch). The mean (in millimeters) over 3 pruritis attacks will be reported.

  4 hours after applying topical cream

Secondary Outcomes (2)

• Time to Itching Intensity Decrease by 50%

  4 hours

• Total Reduction in Itch Intensity

  4 hours

Study Arms (3)

Arm A: Circadian Rhythm of Itch

NO INTERVENTION

For the study arm A, to evaluate circadian rhythm of itching, patients will record for 7 days 6 times daily in a booklet the itch intensity on a visual analog scale (VAS) scale. These time points for itch intensity recording will be hours after time of awakening (AW), so they will be AW+2h, AW+4h, AW+6h, AW+8h, AW+10h, AW+12h. Patients are to document all their pruritus attacks at these time points. On day 8 the investigators will collect suction blisters (4-5 10mm blisters) at these 6 time points from unaffected skin on the trunk. For this purpose, the investigators will use the commercially available 47mm orifice plate (Electronic Diversities, Finksburg MD, USA) with 4-5 x10mm openings for each time point and use the 4-5 1mm blister roofs for harvesting.

Arm B: Topical Naltrexone Cream

EXPERIMENTAL

Patients will start with placebo in week 2 and move on to naltrexone treatment in week 3. There will be a wash-in phase during week 1. Following week 2 and week 3, at visits 3 and 4, patients will be asked for the area where they are experiencing most intense itch and the investigators will take suction blisters from that area before any treatment. They will be told to bring the medication they have been using and they will apply this topically. After an hour, another suction blister will be taken from the same area. This will ensure the study is still blinded as neither the physician or the participant will know whether the medication was a placebo or not. Participants may apply their topical treatment as often as he wishes.

Drug: Naltrexone

Arm C: Placebo Cream

PLACEBO COMPARATOR

Patients will start with naltrexone treatment in week 2 and move on to placebo treatment in week 3. Other than this, all procedures will be the same as in study arm B.

Other: Placebo Cream

Interventions

Naltrexone DRUG

Topical naltrexone cream (1%)

Arm B: Topical Naltrexone Cream

Placebo Cream OTHER

Topical placebo cream

Arm C: Placebo Cream

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of AD via simplified UK Working Group Criteria and a baseline PSGA score of 2 or greater
• Subjects taking hormone-containing medications must be on a stable dose for 6 months prior to study start to avoid any confounding influence on sensory and pain perception

You may not qualify if:

• Use of topical or oral anti-inflammatory medications for 2 weeks prior to the study start
• Use of topical or oral anti-histamines for 2 weeks prior to the study start
• Use of topical or oral anti-pruritic agents for 2 weeks prior to the study start
• Use of oral neuromodulatory agents for 2 months prior to study start
• Current use of chronic pain medications (including opioids, antidepressants and anti-epileptic drugs)
• Use of nicotine-containing products for the past 6 months prior to study start
• History of radiation or chemotherapy
• History of traumatic injury on prospective test sites
• Unstable thyroid function within the past 6 months prior to study start to exclude thyroid-related neuropathy (Duyff et al, 2000)
• Known history of central or peripheral nervous system dysfunction
• History of acute hepatitis, chronic liver disease or end stage liver disease
• History of human immunodeficiency virus (HIV) or acquired immune deficiency syndrome
• History of neuropathy associated with chronic obstructive pulmonary disease, diabetes mellitus, documented exposure to organophosphates or heavy metals or polychlorinated biphenyls
• Known nutritional deficiency (vitamin B12, vitamin D, iron or zinc) within 3 months prior to the study start
• Use of illicit drugs within the past 6 months prior to study start

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Dermatitis, Atopic; Pruritus; Dermatitis

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Paul Bigliardi, MD

  University of Minenesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 6, 2019
• Study Start: October 1, 2020
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2024
• Last Updated: April 20, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)