Back to resultsImpact of Cold Exposure on Metabolic Regulation in Children With Non Alcoholic Fatty Liver Disease (NAFLD) (ICE BAT)
Primary Purpose
Non-Alcoholic Fatty Liver Disease
Status
Unknown status
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
ICE
Sponsored by
About this trial
This is an interventional other trial for Non-Alcoholic Fatty Liver Disease
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Sites / Locations
- Guy's and St Thomas' NHS Foundation Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Intermittent Cold Exposure (ICE)
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
Secondary Outcome Measures
Stage 1: BAT dimensions: Measured using MRI before and after ICE.
Measurement of brown adipose tissue depots will be recorded using MRI scans before and after ICE.
Stage 1: BAT and WAT function: Assessed using MRI measurements before and after ICE.
Using measures of blood flow, fat fraction and water fraction taken during MRI, analysis analysis algorithms are used to distinguish between BAT and WAT, with blood flow measurements used as a surrogate marker of BAT function.
Stage1 : BAT activity: Measured using thermal imaging before and after ICE.
Thermal imaging will be analysed for average temperature of the BAT region of interest and the upper chest area before and after ICE treatment.
Stage 1: Acceptability of study protocol and cooling garment: Measured using an acceptability questionnaire at the end of the study.
As above
Stage 1: Autonomic function measured by the Empatica E4 device for the duration of the study.
As above
Stage 1: Dietary information: Assessed using a 24 hour dietary recall at the beginning of the study day 1.
As above
Stage1: Lipid profile: Measured through analysis of blood spot (collected before and after ICE, mandatory) by a secondary laboratory.
As above
Stage1: Glucose measured before and after ICE (mandatory).
Glucose measured (in mmol/l) before and after ICE.
Stage1: Metabolic hormone profile: Measured before and after ICE (optional).
Metabolic hormones measured before and after ICE, on serum samples by research laboratory.
Stage1: Serum lipids measured before and after ICE (optional).
Serum lipids measured before and after ICE (optional) through Viapath Laboratory, King's College Hospital.
Stage 2: BAT dimensions measured using MRI before and after ICE.
Measurement of brown adipose tissue depots will be recorded using MRI scans before and after ICE, on day 1 for stage 2a and day 1 and day 5 for stage 2b participants.
Stage 2: BAT and WAT function assessed using MRI measurements before and after ICE.
Using measures of blood flow, fat fraction and water fraction taken during MRI, analysis analysis algorithms are used to distinguish between BAT and WAT, with blood flow measurements used as a surrogate marker of BAT function.
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).
As above
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.
As above
Stage 2: Acceptability of study protocol and cooling garment.
Measure using an acceptability questionnaire at the end of the study. The willingness of the participants to attend for 5 days is also a reflection on the acceptability of the study.
Stage 2: Autonomic function measured by the Empatica E4 device.
As above
Stage 2: Activity measured using the Fitbit for NAFLD patients completing 5 days of ICE.
As above
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).
As above
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.
As above.
Stage 2: Serum lipid measurements before and after ICE (optional)
Serum lipids measured before and after ICE (optional) through Viapath Laboratory, King's College Hospital.
Stage 2: Metabolic hormone profile before and after ICE (optional).
Metabolic hormones measured before and after ICE, on serum samples by research laboratory.
Stage 2: Glucose measurements before and after ICE in stage 2 participants
Glucose measurements before and after ICE in mmol/l.
Stage 2: Gut microbiome evaluation in NAFLD participants (optional).
Bacterial DNA will be isolated from faecal samples to study 16S RNA sequencing.
Full Information
NCT ID
NCT04969744
First Posted
June 23, 2021
Last Updated
July 9, 2021
Sponsor
Guy's and St Thomas' NHS Foundation Trust
Collaborators
King's College London, Guts UK, Medical Research Council
1. Study Identification
Unique Protocol Identification Number
NCT04969744
Brief Title
Impact of Cold Exposure on Metabolic Regulation in Children With Non Alcoholic Fatty Liver Disease (NAFLD)
Acronym
ICE BAT
Official Title
Impact of Cold Exposure on Metabolic Regulation in Children With Non Alcoholic Fatty Liver Disease (NAFLD)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Unknown status
Study Start Date
July 2021 (Anticipated)
Primary Completion Date
July 2022 (Anticipated)
Study Completion Date
September 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Guy's and St Thomas' NHS Foundation Trust
Collaborators
King's College London, Guts UK, Medical Research Council
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
Detailed Description
ICE BAT is a single centre pilot study.
In stage 1, 12 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Alcoholic Fatty Liver Disease
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
ICE BAT study will be performed in two stages. In stage 1, we will recruit 12 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).
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intermittent Cold Exposure (ICE)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
ICE
Intervention Description
Intermittent Cooling Exposure using cooling garment for 1-2 hours
Primary Outcome Measure Information:
Title
Stage 1: Effectiveness in participants aged 16-26
Description
Assess the ability to deliver ICE via a cooling garment using a probe to measure skin temperature at regular intervals during ICE treatment.
Time Frame
One day
Title
Stage 1: Acceptability in participants aged 16-26
Description
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.
Time Frame
One day
Title
Stage 2: Effectiveness for 8-16 year old participants.
Description
Assess the ability of ICE to deliver cooling, using a probe to measure skin temperature at regular intervals during ICE treatment.
Time Frame
One to Five days
Title
Stage 2: Acceptability for 8-16 year old participants.
Description
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.
Time Frame
One to Five days
Secondary Outcome Measure Information:
Title
Stage 1: BAT dimensions: Measured using MRI before and after ICE.
Description
Measurement of brown adipose tissue depots will be recorded using MRI scans before and after ICE.
Time Frame
One Day
Title
Stage 1: BAT and WAT function: Assessed using MRI measurements before and after ICE.
Description
Using measures of blood flow, fat fraction and water fraction taken during MRI, analysis analysis algorithms are used to distinguish between BAT and WAT, with blood flow measurements used as a surrogate marker of BAT function.
Time Frame
One Day
Title
Stage1 : BAT activity: Measured using thermal imaging before and after ICE.
Description
Thermal imaging will be analysed for average temperature of the BAT region of interest and the upper chest area before and after ICE treatment.
Time Frame
One Day
Title
Stage 1: Acceptability of study protocol and cooling garment: Measured using an acceptability questionnaire at the end of the study.
Description
As above
Time Frame
One Day
Title
Stage 1: Autonomic function measured by the Empatica E4 device for the duration of the study.
Description
As above
Time Frame
One Day
Title
Stage 1: Dietary information: Assessed using a 24 hour dietary recall at the beginning of the study day 1.
Description
As above
Time Frame
One Day
Title
Stage1: Lipid profile: Measured through analysis of blood spot (collected before and after ICE, mandatory) by a secondary laboratory.
Description
As above
Time Frame
One Day
Title
Stage1: Glucose measured before and after ICE (mandatory).
Description
Glucose measured (in mmol/l) before and after ICE.
Time Frame
One Day
Title
Stage1: Metabolic hormone profile: Measured before and after ICE (optional).
Description
Metabolic hormones measured before and after ICE, on serum samples by research laboratory.
Time Frame
One Day
Title
Stage1: Serum lipids measured before and after ICE (optional).
Description
Serum lipids measured before and after ICE (optional) through Viapath Laboratory, King's College Hospital.
Time Frame
One Day
Title
Stage 2: BAT dimensions measured using MRI before and after ICE.
Description
Measurement of brown adipose tissue depots will be recorded using MRI scans before and after ICE, on day 1 for stage 2a and day 1 and day 5 for stage 2b participants.
Time Frame
One to Five days
Title
Stage 2: BAT and WAT function assessed using MRI measurements before and after ICE.
Description
Using measures of blood flow, fat fraction and water fraction taken during MRI, analysis analysis algorithms are used to distinguish between BAT and WAT, with blood flow measurements used as a surrogate marker of BAT function.
Time Frame
One to Five days
Title
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).
Description
As above
Time Frame
One to Five days
Title
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.
Description
As above
Time Frame
One to Five days
Title
Stage 2: Acceptability of study protocol and cooling garment.
Description
Measure using an acceptability questionnaire at the end of the study. The willingness of the participants to attend for 5 days is also a reflection on the acceptability of the study.
Time Frame
One to Five days
Title
Stage 2: Autonomic function measured by the Empatica E4 device.
Description
As above
Time Frame
One to Five days
Title
Stage 2: Activity measured using the Fitbit for NAFLD patients completing 5 days of ICE.
Description
As above
Time Frame
One to Five days
Title
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).
Description
As above
Time Frame
One to Five days
Title
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.
Description
As above.
Time Frame
One to Five days
Title
Stage 2: Serum lipid measurements before and after ICE (optional)
Description
Serum lipids measured before and after ICE (optional) through Viapath Laboratory, King's College Hospital.
Time Frame
One to Five days
Title
Stage 2: Metabolic hormone profile before and after ICE (optional).
Description
Metabolic hormones measured before and after ICE, on serum samples by research laboratory.
Time Frame
One to Five days
Title
Stage 2: Glucose measurements before and after ICE in stage 2 participants
Description
Glucose measurements before and after ICE in mmol/l.
Time Frame
One to Five days
Title
Stage 2: Gut microbiome evaluation in NAFLD participants (optional).
Description
Bacterial DNA will be isolated from faecal samples to study 16S RNA sequencing.
Time Frame
One to Five days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
26 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Catherine Williamson, Professor
Phone
02078486350
Email
catherine.williamson@kcl.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Dharshene Shivapatham, Masters
Phone
02071887188
Ext
53380
Email
Dharshene.shivapatham@gstt.nhs.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catherine Williamson, Professor
Organizational Affiliation
King's College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Guy's and St Thomas' NHS Foundation Trust
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catherine Williamson, Professor
Phone
02078486350
Email
catherine.williamson@kcl.ac.uk
First Name & Middle Initial & Last Name & Degree
Catherine Williamson, Professor
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
N/A - no plan to share identifiable patient data with other researchers.
Learn more about this trial
Impact of Cold Exposure on Metabolic Regulation in Children With Non Alcoholic Fatty Liver Disease (NAFLD)
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