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

January 30, 2024 updated by: Guy's and St Thomas' NHS Foundation Trust
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United Kingdom
      • London, United Kingdom, SE1 9RT
        • Recruiting
        • Guy's and St Thomas' NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Caroline Ovadia, Doctor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

8 years to 26 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Intermittent Cold Exposure (ICE)
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
Intermittent Cooling Exposure using cooling garment for 1-2 hours

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Stage 1: Effectiveness in participants aged 16-26
Time Frame: 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.
One day
Stage 1: Acceptability in participants aged 16-26
Time Frame: 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.
One day
Stage 2: Effectiveness for 8-16 year old participants.
Time Frame: 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.
One to Five days
Stage 2: Acceptability for 8-16 year old participants.
Time Frame: 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.
One to Five days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Stage 1: BAT dimensions: Measured using MRI before and after ICE.
Time Frame: One Day
Measurement of brown adipose tissue depots will be recorded using MRI scans before and after ICE.
One Day
Stage 1: BAT and WAT function: Assessed using MRI measurements before and after ICE.
Time Frame: One Day
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.
One Day
Stage1 : BAT activity: Measured using thermal imaging before and after ICE.
Time Frame: One Day
Thermal imaging will be analysed for average temperature of the BAT region of interest and the upper chest area before and after ICE treatment.
One Day
Stage 1: Acceptability of study protocol and cooling garment: Measured using an acceptability questionnaire at the end of the study.
Time Frame: One Day
As above
One Day
Stage 1: Autonomic function measured by the Empatica E4 device for the duration of the study.
Time Frame: One Day
As above
One Day
Stage 1: Dietary information: Assessed using a 24 hour dietary recall at the beginning of the study day 1.
Time Frame: One Day
As above
One Day
Stage1: Lipid profile: Measured through analysis of blood spot (collected before and after ICE, mandatory) by a secondary laboratory.
Time Frame: One Day
As above
One Day
Stage1: Glucose measured before and after ICE (mandatory).
Time Frame: One Day
Glucose measured (in mmol/l) before and after ICE.
One Day
Stage1: Metabolic hormone profile: Measured before and after ICE (optional).
Time Frame: One Day
Metabolic hormones measured before and after ICE, on serum samples by research laboratory.
One Day
Stage1: Serum lipids measured before and after ICE (optional).
Time Frame: One Day
Serum lipids measured before and after ICE (optional) through Viapath Laboratory, King's College Hospital.
One Day
Stage 2: BAT dimensions measured using MRI before and after ICE.
Time Frame: One to Five days
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.
One to Five days
Stage 2: BAT and WAT function assessed using MRI measurements before and after ICE.
Time Frame: One to Five days
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.
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).
Time Frame: One to Five days
As above
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.
Time Frame: One to Five days
As above
One to Five days
Stage 2: Acceptability of study protocol and cooling garment.
Time Frame: One to Five days
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.
One to Five days
Stage 2: Autonomic function measured by the Empatica E4 device.
Time Frame: One to Five days
As above
One to Five days
Stage 2: Activity measured using the Fitbit for NAFLD patients completing 5 days of ICE.
Time Frame: One to Five days
As above
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).
Time Frame: One to Five days
As above
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.
Time Frame: One to Five days
As above.
One to Five days
Stage 2: Serum lipid measurements before and after ICE (optional)
Time Frame: One to Five days
Serum lipids measured before and after ICE (optional) through Viapath Laboratory, King's College Hospital.
One to Five days
Stage 2: Metabolic hormone profile before and after ICE (optional).
Time Frame: One to Five days
Metabolic hormones measured before and after ICE, on serum samples by research laboratory.
One to Five days
Stage 2: Glucose measurements before and after ICE in stage 2 participants
Time Frame: One to Five days
Glucose measurements before and after ICE in mmol/l.
One to Five days
Stage 2: Gut microbiome evaluation in NAFLD participants (optional).
Time Frame: One to Five days
Bacterial DNA will be isolated from faecal samples to study 16S RNA sequencing.
One to Five days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Guy's and St Thomas' NHS Foundation Trust

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
King's College London
Medical Research Council
Guts UK

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Caroline Ovadia, Doctor, King's College London

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 23, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 23, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 9, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 21, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 1, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 30, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 278804

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

N/A - no plan to share identifiable patient data with other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Non-Alcoholic Fatty Liver Disease

Clinical Trials on ICE

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings