Impact of Cold Exposure on Metabolic Regulation in Children With Non Alcoholic Fatty Liver Disease (NAFLD)

NCT04969744 | Unknown

• 1 other identifier: 278804
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-Alcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (4)

• Stage 1: Effectiveness in participants aged 16-26

  Assess the ability to deliver ICE via a cooling garment using a probe to measure skin temperature at regular intervals during ICE treatment.

  One day

• Stage 1: Acceptability in participants aged 16-26

  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.

  One day

• Stage 2: Effectiveness for 8-16 year old participants.

  Assess the ability of ICE to deliver cooling, using a probe to measure skin temperature at regular intervals during ICE treatment.

  One to Five days

• Stage 2: Acceptability for 8-16 year old participants.

  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.

  One to Five days

Secondary Outcomes (23)

• Stage 1: BAT dimensions: Measured using MRI before and after ICE.

  One Day

• Stage 1: BAT and WAT function: Assessed using MRI measurements before and after ICE.

  One Day

• Stage1 : BAT activity: Measured using thermal imaging before and after ICE.

  One Day

• Stage 1: Acceptability of study protocol and cooling garment: Measured using an acceptability questionnaire at the end of the study.

  One Day

• Stage 1: Autonomic function measured by the Empatica E4 device for the duration of the study.

  One Day

Study Arms (1)

Intermittent Cold Exposure (ICE)

EXPERIMENTAL

Stage 1- healthy volunteers aged 16-26 years will receive ICE for one day. stage 2a - controls aged 8-16 will receive ICE for one day. Stage 2b- NAFLD patients aged 8-16 years will receive ICE for one day or choose to continue for 5 days.

Device: ICE

Interventions

ICE DEVICE

Intermittent Cooling Exposure using cooling garment for 1-2 hours

Intermittent Cold Exposure (ICE)

Eligibility Criteria

• Age: 8 Years - 26 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Guy's and St Thomas' NHS Foundation Trust: lead
• King's College London: collaborator
• Guts UK: collaborator
• Medical Research Council: collaborator

Study Sites (1)

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Caroline Ovadia, Doctor

  King's College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caroline Ovadia, Doctor

CONTACT

02078486202; caroline.ovadia@kcl.ac.uk

Dharshene Shivapatham, Masters

CONTACT

02071887188; Dharshene.shivapatham@gstt.nhs.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: ICE BAT study will be performed in two stages. In stage 1, we will recruit 12 to 24 healthy volunteers aged between 16-26 years. In stage 2, we will recruit 12 children aged between 8-16 years with NAFLD and 12 age- and sex-matched controls (healthy volunteers).

Study Record Dates

• First Submitted: June 23, 2021
• First Posted: July 21, 2021
• Study Start: October 23, 2021
• Primary Completion: May 1, 2024
• Study Completion: December 1, 2024
• Last Updated: February 1, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)