Using Dupilumab to Improve Circadian Function, Sleep and Pruritus in Children With Moderate/Severe Atopic Dermatitis
Study Details
Study Description
Brief Summary
Single center, prospective, Open label study of sleep, pruritus and circadian function pre/post 12-weeks of dupilumab treatment in children 6-17 years old
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
Subjects will complete two overnight sleep studies, before and after using dupilumab for 12 weeks, to assess the effect of dupilumab on sleep disturbance in eczema patients. These overnight visits will include PSG, blood draws, skin sensors, urine collection, tape stripping, and photography. Subjects will be given dupilumab to use for 12 weeks at home before returning for the second sleep study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dupilumab administration dupilumab administered in weight based dosage for 12 weeks. The drug will be administered once a week during this time through a subcutaneous injection. |
Drug: Dupilumab
12 week dupilumab administration
Other Names:
|
Outcome Measures
Primary Outcome Measures
- PROMIS (Patient Reported Outcome Measurement Information System) parent-proxy score [12 weeks]
Improvement from baseline in PROMIS Parent-Proxy sleep disturbance score (short format 8-item) after 12 weeks post dupilumab initiation. The minimum value is "Never" and the maximum value is "Always". Higher scores mean worse outcomes.
- PROMIS patient score [12 weeks]
Improvement from baseline in PROMIS Patient-reported sleep disturbance score (short format 8-item) after 12 weeks post dupilumab initiation (in children ≥ 8 years old). The minimum value is "Never" and the maximum value is "Always". Higher scores mean worse outcomes.
- Wake After Sleep Onset [12 weeks]
Percentage of patients achieving clinically significant improvement in minutes of Wake After Sleep Onset from baseline to Week 12 on inpatient polysomnography (PSG).
Secondary Outcome Measures
- Sleep Efficiency in the Clinical Sleep Lab [12 weeks]
Change from baseline to Week 12 in percent Sleep Efficiency on PSG.
- Sleep Onset Latency in the Clinical Sleep Lab [12 weeks]
Change from baseline to Week 12 in Sleep Onset Latency in minutes on PSG.
- Total Sleep Time in the Clinical Sleep Lab [12 weeks]
Change from baseline to Week 12 in Total Sleep Time in minutes on PSG.
- Periodic Limb Movement Frequency in the Clinical Sleep Lab [12 weeks]
Change from baseline to Week 12 in periodic limb movement frequency on PSG
- Slow Wave Sleep Time in the Clinical Sleep Lab [12 weeks]
Change from baseline to Week 12 in % of time spent in slow wave sleep (generally stage 3 sleep).
- REM (Rapid Eye Movement) Sleep Time in the Clinical Sleep Lab [12 weeks]
Change from baseline to Week 12 in % of time spent in REM sleep.
- Wake After Sleep Onset (WASO) at Home [12 weeks]
Change from baseline to Week 12 in minutes of WASO averaged over 1-week of outpatient actigraphy.
- Sleep Efficiency at Home [12 weeks]
Change from baseline to Week 12 in percent Sleep Efficiency on actigraphy.
- Sleep Onset Latency at Home [12 weeks]
Change from baseline to Week 12 in Sleep Onset Latency in minutes on actigraphy.
- Total Sleep Time at Home [12 weeks]
Change from baseline to Week 12 in Total Sleep Time in minutes on actigraphy.
- Sleep Disturbance [12 weeks]
Number of weeks it takes to achieve 5-point improvement from baseline in patient/parent-proxy reported sleep disturbance (assessed by weekly PROMIS sleep disturbance measures).
- PROMIS Sleep Assessments [12 weeks]
Percent change from baseline in weekly PROMIS sleep assessments at Weeks 1-12.
- PROMIS Itch Severity [12 weeks]
Percent change from baseline to Week 12 in PROMIS parent-proxy and patient-reported itch severity Numeric Rating Scale (NRS).
- Itch NRS [12 weeks]
Percent change from baseline in weekly Itch NRS at Weeks 1-12.
- PROMIS Itch Intensity [12 weeks]
Percent change from baseline to Week 12 in PROMIS parent-proxy and patient-reported itch intensity and impact assessment (PIQ-C).
- Scratch [12 weeks]
Percent change from baseline to Week 12 in total minutes spent scratching during polysomnography (PSG). Percent change from baseline to Week 12 in number of scratching bouts during polysomnography.
- Eczema Area and Severity Index (EASI) [12 weeks]
Percent change from baseline to Week 12 in Eczema Area and Severity Index (EASI) Score. EASI score objectively measures disease severity. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with higher scores reflecting worse severity.
- Eczema Area and Severity Index 75 (EASI-75) [12 weeks]
Percent of patients with 75% or more improvement from baseline in Eczema Area and Severity Index (EASI-75)
- Patient Oriented Eczema Measure (POEM) [12 weeks]
Percent change from baseline to Week 12 in Patient Oriented Eczema Measure (POEM) by parent-proxy and children report (in patients ≥8yo).
- Children's Dermatology Life Quality Index [12 weeks]
Change from baseline to Week 12 in Children's Dermatology Life Quality Index (CDLQI).
- PROMIS Pediatric Profile [12 weeks]
Change from baseline to Week 12 in PROMIS Pediatric Profile measure (general QOL).
- Inattention Score [12 weeks]
Change from baseline to Week 12 in Inattention Score.
- Amplitude of Skin Barrier Hydration [12 weeks]
Change from baseline to Week 12 in the amplitude of skin barrier hydration during 24 hours of monitoring.
- Peripheral Skin Temperature [12 weeks]
Change from baseline to Week 12 in the peripheral skin temperature during 24 hours of monitoring.
- Amplitude of Melatonin [12 weeks]
Change from baseline to Week 12 in the amplitude of melatonin.
- Transepidermal Water Loss [12 weeks]
Change from baseline to Week 12 in the Transepidermal Water Loss (TEWL) during hourly monitoring while patients are awake.
- CD4+CLA+ and CD8+CLA+ Transcriptome Changes [12 weeks]
Quantify CD4+CLA+ and CD8+CLA+ transcriptome changes from baseline to Week 12 (blood transcriptome).
- Skin-Homing T-Cells [12 weeks]
Determine the presence of changes noted in skin-homing T-cells from baseline to Week 12 in the epidermal transcriptome (skin transcriptome).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participants, 6-17 years old at time of enrollment.
-
Moderate to severe chronic AD inadequately controlled by topical treatment, diagnosed according to Hanifin and Rajka criteria by a pediatric dermatologist or allergist.
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AD severity will be determined at baseline with Validated Investigator Global Assessment (vIGA) score of moderate (3) or severe (4).
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Patient assessed or parent-proxy (under 8 years old) PROMIS sleep disturbance T-score ≥60.
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Willing and able to comply with visits and study-related procedures.
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On stable regimens (consistent use 14 days before Day 1 of study enrollment) of inhaled corticosteroids, topical steroids, and antihistamines.
Exclusion Criteria:
-
Poorly controlled asthma (Asthma Control Test ≤19).
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Self-reported sleep disturbance on 2 or more nights in the past 7 days due to allergic rhinitis.
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Use of concomitant medication that causes scratching.
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Major medical condition (such as cancer).
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Active condition that could affect sleep, such as obstructive sleep apnea, restless leg syndrome, insomnia, narcolepsy, severe sleep disordered breathing, severe depression, COVID-19, or hives (urticaria).
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Having applied topical steroids within 7 days of first or second PSG (important for biomarkers assessment).
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Use of systemic immunosuppressant within 30 days of first PSG.
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Having showered or used moisturizers within 12 hours of first or second PSG.
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Unable to communicate in English (some PROMIS questionnaires not available in translation).
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Other contraindication to receiving dupilumab (such as history of allergic reaction to dupilumab or any of its components).
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Pregnancy.
-
Clinical blindness (circadian disturbing).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Lurie Children's Hospital | Chicago | Illinois | United States | 60611 |
| 2 | Northwestern University | Chicago | Illinois | United States | 60611 |
Sponsors and Collaborators
- Ann & Robert H Lurie Children's Hospital of Chicago
- Northwestern University
Investigators
- Principal Investigator: Anna B Fishbein, MD, Lurie Children's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021-4161