'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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Metabolome swab
研究概览
简要总结
'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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 12 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 12 to 18 with atopic eczema (groups 1 and 2), which has been diagnosed by a Consultant Dermatologist.
- •Patients with atopic eczema warranting systemic immuno-modulatory therapy or patients with atopic eczema on topical therapy or healthy controls.
- •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.
- •Willingness to comply with all study requirements.
- •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).
排除标准
- •Insufficient understanding of the study by the patient and/or parent/guardian.
- •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.
- •Any condition deemed by the Investigator to limit a patient's ability to undertake MRI components of the study, for example significant claustrophobia.
- •Diagnosed by a sleep medicine specialist with a formal sleep disorder, requiring systemic medication.
- •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.
- •Previous and/or current substance misuse.
- •Patients who take medications that would, in the investigator's opinion, impact on quality of sleep studies.
研究组 & 干预措施
Severe eczema
Patients aged 12-18 who have been diagnosed with atopic eczema and require starting systemic therapy.
干预措施: Methotrexate (Drug)
Severe eczema
Patients aged 12-18 who have been diagnosed with atopic eczema and require starting systemic therapy.
干预措施: Dupilumab (Drug)
结局指标
主要结局
Metabolome swab
时间窗: 6 months
Skin metabalome analysis using a skin swab
Eczema Area and Severity Index (EASI) Score
时间窗: 6 months
Clinical assessment of atopic dermatitis disease activity. Range 0-72 (72 being the most severe outcome)
Transepidermal water loss (TEWL)
时间窗: 6 months
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
Peak Pruritus Numerical Rating Score
时间窗: 6 months
Patient reported itch severity. Range 0-10 (10 being the worst outcome)
Skin surface pH
时间窗: 6 months
Skin barrier function measurement using a pH measuring device.
Skin ELISA (enzyme-linked immunosorbent assay) and serum ELISA
时间窗: 6 months
Immunoassay detection and quantification
RNA sequencing of blood serum
时间窗: 6 months
To detect transcript isoforms, gene fusions and single nucleotide variants.
Pediatric Sleep Questionnaire
时间窗: 6 months
Sleep questionnaire. Score 18-126 (126 being the worst clinical outcome)
Morningness-Eveningness Questionnaire
时间窗: 6 months
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.
Patient-Reported Outcomes Measurement Information System (PROMIS)
时间窗: 6 months
Sleep questionnaire. Score 0-20 (0 being the worst clinical outcome)
Pittsburgh Sleep Quality Index
时间窗: 6 months
Sleep questionnaires. Score 0-21 (21 being the worst clinical outcome)
Dreem headband electroencephalogram monitoring
时间窗: 6 months
Sleep study - Measures brain activity to assess sleep cycles
Polysomnography
时间窗: 6 months
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.
Actigraphy Watch analysis
时间窗: 6 months
Watch is worn by participant which records movement during sleep to analyse sleep pattern
EMFIT mattress analysis
时间窗: 6 months
Mattress sensor which records movement during sleep to analyse sleep pattern to analyse sleep pattern
Wechsler Abbreviated Scale of Intelligence Second Edition (WASI-II) Score
时间窗: 6 months
Intelligence Quotient Test. Score 40-160 (40 being the worst clinical outcome)
Go/No-GO Task
时间窗: 6 months
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.
Simon Task
时间窗: 6 months
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.
Continuous Performance Task
时间窗: 6 months
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.
Time Discrimination Task
时间窗: 6 months
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.
Vigilance Task (Mackworth Clock)
时间窗: 6 months
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.
Performance on Working Memory Task
时间窗: 6 months
Completed in functional MRI
Performance on Sustained Attention Task
时间窗: 6 months
Completed in functional MRI
Resting Brain State
时间窗: 6 months
Measured in functional MRI
Structural Changes in the Brain
时间窗: 6 months
Structure of the brain is measured in MRI
次要结局
未报告次要终点