Mind and Skin - the Neurocutaneous Axis in Atopic Eczema

Atopic Dermatitis Clinical Trial

Official title:

'Mind and Skin': A Prospective Cohort Study Evaluating the Impact of Inflammation, Itch and Sleep Disturbance on the Brain, Mental Health and Cognition, in Patients With Severe Atopy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05790330
• Other study ID #: 280154
• Status: Recruiting
• Start date: March 10, 2023
• Est. completion date: June 1, 2027

Study information

• Verified date: May 2024
• Source: King's College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

'Mind and Skin': A prospective cohort study evaluating the impact of inflammation, itch and sleep disturbance on the brain, mental health and cognition, in patients with severe atopy.

Description:

Atopic eczema is an intensely itchy skin disease which often starts in infancy or early childhood. It can have profound effects on patients' quality of life and cause long-lasting psychological impairment. Sleep may be very disturbed. More severe disease often requires oral/injectable immuno-modulatory treatments (i.e. medications which control symptoms by influencing the immune system).

There is an association between eczema, impaired cognitive functioning and mental health disorders, but the underlying mechanisms are not clearly defined.

This projects examines the links between inflammation-driven itching and disturbed sleep, and how this might be causally responsible for systemic and brain inflammation, disturbance of cognitive functioning and mental health problems. The investigators will also study potential changes occurring following an improvement in eczema when patients are treated with systemic immuno-modulators.

Key investigations will include:

i) Home-based sleep studies using a commercially available sleep devices (for example DREEM headband, Philips Actiwatch, oximetry) ii) Structural and functional magnetic resonance imaging (MRI) of the brain, iii) Blood tests to quantify systemic inflammation iv) Genetic analyses, particularly related to the immune system, circadian rhythm (the "internal 24-hour clock"), skin barrier function and the risk of developing eczema or associated diseases, v) Assessments of the skin's barrier function vi) Stool samples and skin swabs to study the gut and skin microbiome.

The investigators will utilise existing anonymised data for comparative purposes (e.g. from patients with Attention Deficit Hyperactivity Disorder (ADHD) and healthy controls who previously had brain imaging.)

The investigators will explore eczema patients' and families' perception of their disease, in particular itch and the resulting sleep loss, through focus groups, to better understand the sociological impact of eczema, and how these patients' interactions with the external world and society are affected by eczema. Importantly, this will include exploration of family dynamics, as patients with eczema often have profound sleep disturbance from early life, which can impact on their caregivers' sleep and quality of life.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: June 1, 2027
• Est. primary completion date: December 1, 2025
• Gender: All
• Age group: 12 Years to 18 Years

Eligibility

Inclusion Criteria:

1. Patients aged 12 to 18 with atopic eczema (groups 1 and 2), which has been diagnosed by a Consultant Dermatologist.

2. Patients with atopic eczema warranting systemic immuno-modulatory therapy or patients with atopic eczema on topical therapy or healthy controls.

3. Written informed consent for study participation obtained from the patient or from the parent(s) / legal guardian, with assent as determined by the patient's age and level of understanding.

4. Willingness to comply with all study requirements.

5. Competent use of English language, according to patient's age (patients will be required to understand the written questionnaires and complying with instructions during MRI scanning).

Exclusion Criteria:

1. Insufficient understanding of the study by the patient and/or parent/guardian.

2. Any clear contra-indication to MRI scanning. In particular this would be due to the presence of any implanted devices or metal from previous surgery or accident. This would be fully assessed with a standardised safety questionnaire by a radiographer prior to MRI scanning.

3. Any condition deemed by the Investigator to limit a patient's ability to undertake MRI components of the study, for example significant claustrophobia.

4. Diagnosed by a sleep medicine specialist with a formal sleep disorder, requiring systemic medication.

5. Sleep disturbance from co-morbid illness (including physical and/or mental/psychological illness) other than atopic eczema, deemed by the Investigator to significantly impact on sleep components of the study.

6. Previous and/or current substance misuse.

7. Patients who take medications that would, in the investigator's opinion, impact on quality of sleep studies.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis

Intervention

Drug:
• Methotrexate
As per usual standard of care
• Dupilumab
As per usual standard of care

Locations

Country	Name	City	State
United Kingdom	Unit for Paediatric and Population-based Dermatology Research	London

Sponsors (2)

Lead Sponsor	Collaborator
King's College London	Guy's and St Thomas' NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Eczema Area and Severity Index (EASI) Score	Clinical assessment of atopic dermatitis disease activity. Range 0-72 (72 being the most severe outcome)	6 months
Primary	Peak Pruritus Numerical Rating Score	Patient reported itch severity. Range 0-10 (10 being the worst outcome)	6 months
Primary	Transepidermal water loss (TEWL)	Skin barrier function measurement using a device which measures the amount of water that passively evaporates through skin to the external environment due to water vapor pressure gradient on both sides of the skin barrier	6 months
Primary	Skin surface pH	Skin barrier function measurement using a pH measuring device.	6 months
Primary	Metabolome swab	Skin metabalome analysis using a skin swab	6 months
Primary	Skin ELISA (enzyme-linked immunosorbent assay) and serum ELISA	Immunoassay detection and quantification	6 months
Primary	RNA sequencing of blood serum	To detect transcript isoforms, gene fusions and single nucleotide variants.	6 months
Primary	Pediatric Sleep Questionnaire	Sleep questionnaire. Score 18-126 (126 being the worst clinical outcome)	6 months
Primary	Morningness-Eveningness Questionnaire	Sleep questionnaire. Score 16-86 assesses individual differences in morningness and eveningness - the degree to which respondents are active and alert at certain times of day.	6 months
Primary	Patient-Reported Outcomes Measurement Information System (PROMIS)	Sleep questionnaire. Score 0-20 (0 being the worst clinical outcome)	6 months
Primary	Pittsburgh Sleep Quality Index	Sleep questionnaires. Score 0-21 (21 being the worst clinical outcome)	6 months
Primary	Dreem headband electroencephalogram monitoring	Sleep study - Measures brain activity to assess sleep cycles	6 months
Primary	Polysomnography	Sleep study incorporating electroencephalogram, electro-oculogram, electromyogram, electrocardiogram, and pulse oximetry, as well as airflow and respiratory effort, to evaluate for underlying causes of sleep disturbances.	6 months
Primary	Actigraphy Watch analysis	Watch is worn by participant which records movement during sleep to analyse sleep pattern	6 months
Primary	EMFIT mattress analysis	Mattress sensor which records movement during sleep to analyse sleep pattern to analyse sleep pattern	6 months
Primary	Wechsler Abbreviated Scale of Intelligence Second Edition (WASI-II) Score	Intelligence Quotient Test. Score 40-160 (40 being the worst clinical outcome)	6 months
Primary	Go/No-GO Task	The Go/No-go task requires participants to respond by pressing a button when they see a "go" signal, and not respond when they see the "no-go" signal. The key behaviour measured with this experiment is the participants' ability to withhold a response on No-go trials. This is scored as a fraction of correct responses.	6 months
Primary	Simon Task	In this task participants are asked to respond to visual stimuli by making a rightward response to one stimulus (e.g. a circle) and a leftward response to another (e.g. a square). This is scored as a fraction of correct responses.	6 months
Primary	Continuous Performance Task	In this task participants are asked to only respond to a specific sequence of visual stimuli. This is scored as a fraction of correct responses.	6 months
Primary	Time Discrimination Task	In this task participants are ask to decide which stimuli stayed on screen for the longest duration. This is scored as a fraction of correct responses.	6 months
Primary	Vigilance Task (Mackworth Clock)	In this task participants are asked to watched a clock hand that moves every second around the clock. From time to time the hand skips a second and participants need to respond to this. This is scored as a fraction of correct responses.	6 months
Primary	Performance on Working Memory Task	Completed in functional MRI	6 months
Primary	Performance on Sustained Attention Task	Completed in functional MRI	6 months
Primary	Resting Brain State	Measured in functional MRI	6 months
Primary	Structural Changes in the Brain	Structure of the brain is measured in MRI	6 months