Treatment of Chronic Itch in Atopic Dermatitis With Opioid Antagonist Naltrexone

NCT04325802 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: DERM-2019-28471
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose: 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 opioid antagonists in atopic dermatitis. In this study, the investigators aim to examine chronic sensory disorder mechanisms related to chronic itch.

Conditions

Atopic Dermatitis; Pruritus; Pruritus Chronic; Dermatitis

Keywords

Chronic Itch

Outcome Measures

Primary Outcomes (1)

• Change in Itch Intensity (Visual Analog Scale)

  Change in itch intensity will be measured using a Visual Analogue scale (VAS). Scores range from 0 to 10, with higher scores indicating greater itch intensity.

  1 week

Study Arms (3)

Cohort 1: Placebo, then Intervention

EXPERIMENTAL

Patients will start with placebo in week 1 and cross over to Naltrexone in week 3. There will be a wash-out phase during week 2 using only moisturizer regularly and if necessary as rescue medications topical corticosteroids and/or antihistamines. The same rescue medications can be used during the following weeks of the cross-over treatment. At visit 2 and 4 patients will be asked the area where they are experiencing most intense itch and we will take there suction blisters (preferably on the trunk). Suction blisters will be taken after week 1 (1 week on treatment arm 1) and after week 3 (1 week on treatment arm 2).

Drug: Naltrexone; Other: Placebo

Cohort 2: Intevention, then Placebo

ACTIVE COMPARATOR

Patients will start with Naltrexone in week 1 and cross over to the palcebo treatment in week 3. There will be a wash-out phase during week 2 using only moisturizer regularly and if necessary as rescue medications topical corticosteroids and/or antihistamines. The same rescue medications can be used during the following weeks of the cross-over treatment. At visit 2 and 4 patients will be asked the area where they are experiencing most intense itch and we will take there suction blisters (preferably on the trunk). Suction blisters will be taken after week 1 (1 week on treatment arm 1) and after week 3 (1 week on treatment arm 2).

Drug: Naltrexone; Other: Placebo

Circadian Rhythm of Itch

NO INTERVENTION

Patients in this arm will receive no intervention, only data collection.

Interventions

Naltrexone DRUG

50mg Naltrexone daily

Cohort 1: Placebo, then Intervention; Cohort 2: Intevention, then Placebo

Placebo OTHER

Placebo (Mannitol) daily

Cohort 1: Placebo, then Intervention; Cohort 2: Intevention, then Placebo

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
• Willingness to adhere to study protocol
• 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 (as rescue medication allowed).
• 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
• 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 and/or opioid use disorder.

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 Minnesota

  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: March 25, 2020
• First Posted: March 30, 2020
• Study Start: December 31, 2022
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: April 4, 2023

Record last verified: 2023-03

Locations

US (1)