Atopic DermatitisPhase 2NCT04325802
Treatment of Chronic Itch in Atopic Dermatitis With Opioid Antagonist Naltrexone
A Phase 2 study testing Naltrexone in people with Atopic Dermatitis and Pruritus, run by University of Minnesota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Atopic Dermatitis, Pruritus, Pruritus Chronic
- What is being tested?
- Naltrexone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Dec 2022to Jun 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
- Regular use of opioids for chronic pain
- Lyme disease, porphyria, rheumatoid arthritis, Hansen's disease (leprosy) or use of antineoplastic chemotherapeutic agents.
- Subject has any medical condition that, in the judgment of the Investigator, would jeopardize the subject's safety following exposure to the administered medications.
- Adults lacking capacity to consent
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Treatment of Chronic Itch in Atopic Dermatitis With Opioid Antagonist Naltrexone and Effects on Skin Circadian Rhythm
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.
Read the detailed description
Specific aims:
A1 Evaluate the underlying mechanism of itch severity in terms of circadian rhythm by collecting epidermis at different circadian stages using suction blisters. This will be done in AD patients with chronic itch. The cells will be isolated from part of the suction blisters and used to isolate and sequence RNA to evaluate and compare the differential protein and RNA expression in suction blister taken from symptomatic \& non-symptomatic areas in patients with AD at different time points. The investigators will then correlate the itch severity symptoms to clock gene and opioid receptor levels and RNA expression differential pattern. A1 will be evaluated by study arm A and the results from this study will serve to decide on time point taking the suction blisters for the therapeutic/mechanistic studies (arm B and C).
A2 Investigate the mechanistic role and therapeutic efficacy of opioid receptors in chronic itch. For this purpose, a cross-over, placebo-controlled design will be used to treat patients with opioid receptor antagonist (Naltrexone) by expanding on our existing trial. The investigators will collect, evaluate, quantify and compare the differential protein and RNA expression in epidermis taken by suction blisters from symptomatic and non-symptomatic areas in patients with AD on Placebo or Naltrexone treatment. Transcriptome analysis will be focused, but not restricted to, analysis of neuroinflammatory and neuronal markers (including cytokines, GPCR and opioid receptors). Confirmation will occur using in-situ hybridization of biopsies to correlate specific cell type and location and qPCR expression of in vitro cultures. The binding studies using fluorescent labeled opioid ligands and internalization pattern will be carried out.
A3 Test the underlying mechanisms of the opioid system with nerve-keratinocyte interaction and possible effects on itch transduction from skin to nerves by using an in vitro neuron-keratinocyte co-culture model. Moreover, the investigators plan to validate itch-causing networks and pathways found in A2 using this in vitro model and will be able to evaluate calcium flux threshold changes after exposure to external stimuli (e.g. light, or mechanic stimuli) onto keratinocytes and neuronal somata under different opioid exposure conditions. The FC derived sensory neurons will be co-cultured with different patient KC. The investigators will test the reaction pattern of KC and transmission of the signal to connected peripheral sensory neurons by Fluo-4 AM Calcium imaging and electrophysiology. The reaction will be responding to the odorant Sandalore, as the investigators have previously published that Sandalore induces these desired calcium fluxes.
Apply the in vitro epithelial/nerve model to validate possible itch pathways identified by epigenetic analysis in the clinical trials by confirming the expression pattern with qPCR and functional assays on cells with CRISPR knockout of the RNA targets, opioid trafficking, calcium imaging and electrophysiology. Finally, further develop co-cultures between human skin and iPS-derived human peripheral neurons to perform functional studies.
- Conditions
- Atopic Dermatitis, Pruritus, Pruritus Chronic, Dermatitis
- Being tested
- Naltrexone, Placebo
- Keywords
- Chronic Itch
- Medical subject headings
- Dermatitis, Atopic, Pruritus, Dermatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaltrexoneDrug
50mg Naltrexone daily
PlaceboOther
Placebo (Mannitol) daily
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: Naltrexone; Other: Placebo |
| Circadian Rhythm of Itch | No intervention | Patients in this arm will receive no intervention, only data collection. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2020
- Study start31 Dec 2022 (estimated)
- Primary completionJun 2024 (estimated)
- Study completionJun 2024 (estimated)
Why it stopped: Covid-19 pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atopic DermatitisStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul Bigliardi, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04325802
- Sponsor's protocol ID
- DERM-2019-28471
- Status last verified
- Mar 2023
- First submitted
- 25 Mar 2020
- Last updated
- 4 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Chronic Itch in Atopic Dermatitis With Opioid Antagonist Naltrexone and Effects on Skin Circadian Rhythm
- ClinicalTrials.gov ID
- NCT04325802
- Acronym / sponsor ID
- DERM-2019-28471
- Conditions
- Atopic Dermatitis, Pruritus, Pruritus Chronic, Dermatitis
- Keywords
- Chronic Itch
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Covid-19 pandemic
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- 31 Dec 2022 (estimated)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Jun 2024 (estimated)
- First posted
- 30 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Specific aims:
A1 Evaluate the underlying mechanism of itch severity in terms of circadian rhythm by collecting epidermis at different circadian stages using suction blisters. This will be done in AD patients with chronic itch. The cells will be isolated from part of the suction blisters and used to isolate and sequence RNA to evaluate and compare the differential protein and RNA expression in suction blister taken from symptomatic \& non-symptomatic areas in patients with AD at different time points. The investigators will then correlate the itch severity symptoms to clock gene and opioid receptor levels and RNA expression differential pattern. A1 will be evaluated by study arm A and the results from this study will serve to decide on time point taking the suction blisters for the therapeutic/mechanistic studies (arm B and C).
A2 Investigate the mechanistic role and therapeutic efficacy of opioid receptors in chronic itch. For this purpose, a cross-over, placebo-controlled design will be used to treat patients with opioid receptor antagonist (Naltrexone) by expanding on our existing trial. The investigators will collect, evaluate, quantify and compare the differential protein and RNA expression in epidermis taken by suction blisters from symptomatic and non-symptomatic areas in patients with AD on Placebo or Naltrexone treatment. Transcriptome analysis will be focused, but not restricted to, analysis of neuroinflammatory and neuronal markers (including cytokines, GPCR and opioid receptors). Confirmation will occur using in-situ hybridization of biopsies to correlate specific cell type and location and qPCR expression of in vitro cultures. The binding studies using fluorescent labeled opioid ligands and internalization pattern will be carried out.
A3 Test the underlying mechanisms of the opioid system with nerve-keratinocyte interaction and possible effects on itch transduction from skin to nerves by using an in vitro neuron-keratinocyte co-culture model. Moreover, the investigators plan to validate itch-causing networks and pathways found in A2 using this in vitro model and will be able to evaluate calcium flux threshold changes after exposure to external stimuli (e.g. light, or mechanic stimuli) onto keratinocytes and neuronal somata under different opioid exposure conditions. The FC derived sensory neurons will be co-cultured with different patient KC. The investigators will test the reaction pattern of KC and transmission of the signal to connected peripheral sensory neurons by Fluo-4 AM Calcium imaging and electrophysiology. The reaction will be responding to the odorant Sandalore, as the investigators have previously published that Sandalore induces these desired calcium fluxes.
Apply the in vitro epithelial/nerve model to validate possible itch pathways identified by epigenetic analysis in the clinical trials by confirming the expression pattern with qPCR and functional assays on cells with CRISPR knockout of the RNA targets, opioid trafficking, calcium imaging and electrophysiology. Finally, further develop co-cultures between human skin and iPS-derived human peripheral neurons to perform functional studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Placebo, then Intervention | Experimental | Drug: Naltrexone, Other: PlaceboPatients 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). |
| Cohort 2: Intevention, then Placebo | Active comparator | Drug: Naltrexone, Other: PlaceboPatients 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). |
| Circadian Rhythm of Itch | No intervention | –Patients in this arm will receive no intervention, only data collection. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (19 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Naltrexone50mg Naltrexone daily | Drug | Cohort 1: Placebo, then Intervention, Cohort 2: Intevention, then Placebo |
| PlaceboPlacebo (Mannitol) daily | Other | Cohort 1: Placebo, then Intervention, Cohort 2: Intevention, then Placebo |
Primary outcome
Change in Itch Intensity (Visual Analog Scale)
Time frame: 1 week
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Bigliardi, MD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Naltrexone in people with Atopic Dermatitis and Pruritus, run by University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 4 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Itch Intensity (Visual Analog Scale) (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2023.