Impact of Cold Exposure on Metabolic Regulation in Children With Non Alcoholic Fatty Liver Disease (NAFLD)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Stage 2: Effectiveness for 8-16 year old participants.
研究概览
简要总结
The aim of this project is to generate pilot data for a grant proposal to evaluate the impact of intermittent cold exposure (ICE) on brown and white adipose tissue (BAT/WAT) function in children with non-alcoholic fatty liver disease (NAFLD). The condition NAFLD is the most common liver disease in both adults and children. There are many emerging drug therapies for NAFLD but at considerable cost in terms of potential side effects. In a mouse model of diet-induced obesity, ICE was shown to help activate BAT, which may help NAFLD and other obesity associated health risks. Given that children have more BAT than adults, we hypothesise that intermittent cold exposure via a cooling vest in children with NAFLD will increase BAT stores or function. We will investigate whether intermittent cold exposure via a cooling vest device will stimulate BAT and also establish whether the cooling vest is acceptable to children and young people. If it is acceptable and has an impact on BAT function this could be a new treatment to reduce the severity of metabolic disorders associated with obesity, particularly fatty liver, e.g. hepatic steatosis. In stage 1, we will investigate the impact of intermittent cold exposure (ICE) on brown and white adipose tissue (BAT/WAT) function in young people aged 16 to 26 years old, as a feasibility study to optimise the cooling process. In stage 2, we will investigate the impact of ICE on BAT and WAT function in 8-16 year olds with non-alcoholic fatty liver disease (NAFLD) and matched controls. Participants will have thermal imaging, MRI scans and provide samples before and after wearing the cooling vest.
详细描述
ICE BAT is a single centre pilot study.
In stage 1, 12 to 24 young people aged 16-26 will be recruited into the study. Participants will use a cooling garment (for 1-2 hours). MRI scans and thermal imaging will be performed before and after ICE to evaluate BAT size and activation. Liver steatosis will be evaluated using MRI Proton Dense Fat Fraction (PDFF). Serum markers of BAT activation and glucose/lipid metabolism will be measured before and after ICE.
In stage 2,12 children with NAFLD and 12 age- and sex-matched controls will be enrolled in the study. In stage 2a, healthy controls will use a cooling garment (for 1-2 hours) and undergo MRI scan and thermal imaging before and after ICE to evaluate BAT size and activation. Liver steatosis will be evaluated using MRI PDFF. In stage 2b the NAFLD patients will be asked to attend for one day and if they are happy to continue, will use a cooling garment (for 1-2 hours/day for a further 4 days). MRI scans and thermal imaging will be performed before and after ICE on day 1 and day 5 to evaluate BAT size and activation. Liver steatosis will be evaluated using MRI PDFF. Serum markers of BAT activation and glucose/lipid metabolism will be measured on day 1 and day 5. Participants with NAFLD, will be asked to give a faecal sample for analysis of their gut microbiome before the study and after day 5 of ICE treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 8 Years 至 26 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Stage 1: Young Adult 16-26 year olds
- •Individual must be aged 16-26 years
- •Individual who has voluntarily signed informed consent
- •Stage 2: Children 8-16 year olds
- •Child aged 8-16 years old with NAFLD attending the paediatric clinic at Kings College Hospital
- •A control group of children with a BMI z score <1.5 and no diagnosis of liver disease
- •Individual willing to participate in the study with informed consent. If the participant is under 16, the parent should provide informed consent.
排除标准
- •Stage 1: Young Adult 16-26 year olds
- •Individual who is thought to be too unwell to participate by the study team, e.g. if participant has a fever or infection requiring treatment with antibiotics.
- •Individual who has a medical condition that requires treatment with a drug that could alter BAT function, e.g. thyroid disease (thyroxine, carbimazole, propylthiouracil, beta- blockers), liver disease (ursodeoxycholic acid), any condition requiring treatment with peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists or 4 beta 3 adrenoceptor (β3-AR) agonists.
- •Individual has smoked/vaped 5 days before participating in the study.
- •Stage 2: Children 8-16 year olds
- •Participant who is thought to be too unwell to participate by the study team, e.g. if participant has a fever or infection requiring treatment with antibiotics.
- •Individual who has a medical condition that requires treatment with a drug that could alter BAT function, e.g. thyroid disease (thyroxine, carbimazole, propylthiouracil, beta- blockers), liver disease (ursodeoxycholic acid), any condition requiring treatment with peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists or 4 beta 3 adrenoceptor (β3-AR) agonists
- •Individual has smoked/vaped 5 days before participating in the study
结局指标
主要结局
Stage 2: Effectiveness for 8-16 year old participants.
时间窗: One to Five days
Assess the ability of ICE to deliver cooling, using a probe to measure skin temperature at regular intervals during ICE treatment.
Stage 1: Effectiveness in participants aged 16-26
时间窗: One day
Assess the ability to deliver ICE via a cooling garment using a probe to measure skin temperature at regular intervals during ICE treatment.
Stage 1: Acceptability in participants aged 16-26
时间窗: One day
Acceptability will be measured by the sum of participants' responses to questions 1-5 of the questionnaire. Responses to individual items will also be presented.
Stage 2: Acceptability for 8-16 year old participants.
时间窗: One to Five days
Acceptability of the cooling jacket will be measured by the sum of participants' responses to questions 1-5 of the questionnaire. Responses to individual items will also be presented. Patients will be given the choice as to whether they are willing to attend for 5 days and undergo a further MRI, thermal imaging and blood sampling on day 5.
次要结局
- Stage 1: Acceptability of study protocol and cooling garment: Measured using an acceptability questionnaire at the end of the study.(One Day)
- Stage 1: BAT and WAT function: Assessed using MRI measurements before and after ICE.(One Day)
- Stage 1: Autonomic function measured by the Empatica E4 device for the duration of the study.(One Day)
- Stage 2: Acceptability of study protocol and cooling garment.(One to Five days)
- Stage 2: Dietary information: Assessed using a 24 hour dietary recall, completed at the beginning of study day 1 (and on Day 5 for NAFLD patients who continue to five days).(One to Five days)
- Stage 2: BAT activity: Measured using thermal imaging before and after ICE on day 1 for stage 2a and day 1 and day 5 for stage 2b participants.(One to Five days)
- Stage 2: Glucose measurements before and after ICE in stage 2 participants(One to Five days)
- Stage 1: BAT dimensions: Measured using MRI before and after ICE.(One Day)
- Stage1 : BAT activity: Measured using thermal imaging before and after ICE.(One Day)
- Stage 1: Dietary information: Assessed using a 24 hour dietary recall at the beginning of the study day 1.(One Day)
- Stage1: Lipid profile: Measured through analysis of blood spot (collected before and after ICE, mandatory) by a secondary laboratory.(One Day)
- Stage1: Metabolic hormone profile: Measured before and after ICE (optional).(One Day)
- Stage1: Serum lipids measured before and after ICE (optional).(One Day)
- Stage 2: Serum lipid measurements before and after ICE (optional)(One to Five days)
- Stage 2: BAT and WAT function assessed using MRI measurements before and after ICE.(One to Five days)
- Stage 2: Liver fat fraction(proton dense fat fraction (PDFF)): Measured in percentage using MRI before ICE on day 1 for stage 2a and before ICE on day 1 and after ICE on day 5 for stage 2b (PDFF measured using MRI).(One to Five days)
- Stage 2: Lipid profile: Measured through analysis of blood spot (collected before and after ICE on day 1 for stage 2a and day 1 and day 5 for stage 2b, mandatory) by an external laboratory.(One to Five days)
- Stage 2: Metabolic hormone profile before and after ICE (optional).(One to Five days)
- Stage1: Glucose measured before and after ICE (mandatory).(One Day)
- Stage 2: BAT dimensions measured using MRI before and after ICE.(One to Five days)
- Stage 2: Autonomic function measured by the Empatica E4 device.(One to Five days)
- Stage 2: Activity measured using the Fitbit for NAFLD patients completing 5 days of ICE.(One to Five days)
- Stage 2: Gut microbiome evaluation in NAFLD participants (optional).(One to Five days)