Atopic Dermatitis Clinical Trial
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.
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. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT05018806 -
Proof of Concept Study of Rilzabrutinib in Adult Patients With Moderate-to-severe Atopic Dermatitis
|
Phase 2 | |
| Terminated |
NCT03847389 -
Clobetasol Topical Oil for Children With Moderate to Severe Atopic Dermatitis
|
Phase 1/Phase 2 | |
| Completed |
NCT04090229 -
A Multi-center, Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of Subcutaneously Delivered ASLAN004 in Adults With Moderate-Severe Atopic Dermatitis
|
Phase 1 | |
| Active, not recruiting |
NCT05388760 -
Tralokinumab Monotherapy for Children With Moderate-to-severe Atopic Dermatitis - TRAPEDS 1 (TRAlokinumab PEDiatric Trial no. 1)
|
Phase 2 | |
| Completed |
NCT05530707 -
Evaluation of Acceptability, Skin Barrier Restoration and Balance of Atopic Skin Using Moisturizer
|
N/A | |
| Completed |
NCT02595073 -
Clinical Study to Evaluate the Efficacy and Safety of Desoximetasone (DSXS) With Atopic Dermatitis
|
Phase 3 | |
| Recruiting |
NCT05509023 -
Evaluating Safety and Efficacy of ADX-914 in Patients With Moderate to Severe Atopic Dermatitis (SIGNAL-AD)
|
Phase 2 | |
| Recruiting |
NCT05048056 -
Phase 2 Study of Efficacy and Safety of AK120, in Subjects With Moderate-to-Severe Atopic Dermatitis
|
Phase 2 | |
| Completed |
NCT04598269 -
Study of ATI-1777 in Adult Patients With Moderate or Severe Atopic Dermatitis
|
Phase 2 | |
| Recruiting |
NCT03936335 -
An Observational Retrospective Cohort Study Being Conducted in Women With Atopic Dermatitis (AD)
|
||
| Withdrawn |
NCT03089476 -
Evaluating Skin Barrier Dysfunction in Infants at High Risk of Atopy
|
N/A | |
| Recruiting |
NCT05029895 -
A Study to Evaluate Adverse Events and Change in Disease State of Oral Upadacitinib in Adolescent Participants Ages 12 to <18 Years Old Diagnosed With Atopic Dermatitis (AD)
|
||
| Terminated |
NCT03654755 -
Study to Evaluate Long-Term Safety of ASN002 in Subjects With Moderate to Severe Atopic Dermatitis
|
Phase 2 | |
| Completed |
NCT04556461 -
Effects of Tralokinumab Treatment of Atopic Dermatitis on Skin Barrier Function
|
Phase 2 | |
| Recruiting |
NCT04818138 -
BROadband vs Narrowband photoTherapy for Eczema Trial Nested in the CACTI Cohort
|
N/A | |
| Completed |
NCT03719742 -
A Clinical Study to Evaluate the Safety and Efficacy of a Baby Cleanser and a Moisturizer
|
N/A | |
| Completed |
NCT05375955 -
A Study to Learn About The Study Medicine (PF-07038124) In Patients With Mild To Moderate Atopic Dermatitis Or Mild To Severe Plaque Psoriasis.
|
Phase 2 | |
| Completed |
NCT03441568 -
In-home Use Test of the New Modified Diprobase Formulation to Assess the Safety and Tolerability in Infants and Children Under Physician's Control
|
N/A | |
| Recruiting |
NCT06366932 -
Optimization of Atopic Dermatitis Treatment That Requires Second-line Systemic Therapy Through Predictive Models
|
Phase 4 | |
| Completed |
NCT03304470 -
A Study to Evaluate the Safety and Efficacy of ATx201 in Subjects With Moderate Atopic Dermatitis
|
Phase 2 |