Condition category
Nutritional, Metabolic, Endocrine
Date applied
05/11/2018
Date assigned
04/12/2018
Last edited
04/12/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Obesity has reached epidemic proportions worldwide and is the driving force behind an equally alarming explosion of type 2 diabetes and cardiovascular (heart) disease. While our ‘obesogenic’ environment - with abundant energy-dense foods and sedentary (inactive) lifestyle – plays a central role in the development of obesity and cardiometabolic diseases, it is also recognized that factors operating during fetal life (before birth) - and resulting in low birth weight - may program the individual for greater susceptibility towards the development of excess fat and type 2 diabetes and cardiovascular diseases later in life. There is indeed compelling evidence - from large population and clinical studies - that adults who had low birth weight (which reflects limitations in optimal growth as a fetus) have higher susceptibility for obesity, type 2 diabetes or cardiovascular diseases, particularly when catch-up growth occurs early after birth. This work forms the basis of the Barker Hypothesis, which states that growth retardation in the uterus, low birth weight, and premature birth are all linked to greater risk of high blood pressure, heart disease and diabetes in middle age. These risks for cardiometabolic disease have been shown across various populations worldwide and within different ethnic groups. The mechanisms by which such early growth patterns (relatively slow growth followed by catch-up growth) predispose to obesity and insulin-related diseases remain unclear, but have been proposed to be due to fetal or neonatal programming for a thrifty (energy-saving) state. According to the Thrifty Phenotype Hypothesis, early growth constraint (due to inadequate nutrition, small womb size, maternal smoking or other factors) can lead to adaptations that reduce the detrimental effects of growth retardation on vital tissues/organ development and functions. If these adaptations take place during critical windows of development, they may become permanent, and may continue even during improved nutrition later in life, thereby predisposing the individual to diseases such as diabetes and cardiovascular disease. This study seeks to find out to what extent young and healthy adults with low birth weight have energy saving characteristics. These adaptations could favor the development of obesity due to a reduction in the ability to burn calories, as well as a lower body temperature. This study aims to answer the following main questions: Do young adults born with a low birth weight have reduced energy expenditure? In response to food (sugar, protein) or physical activities of daily life, are these young adults different than those born with normal birth weight in terms of their energy expenditure? Is central body temperature lower in young adults with low birth weight than in those born with normal birth weight?

Who can participate?
Healthy volunteers aged 18-35 whose birth weight was in the range of 1.5 – 3.5 kg

What does the study involve?
Participants are instructed to refrain from heavy exercise and from drinking caffeinated drinks and alcohol on the day before each experiment, and to eat a normal meal on the evening before the experiment. Women are only tested during the follicular phase of their menstrual cycle. In addition to the days scheduled for test experiments, participants come to the laboratory for two short preliminary visits. On the 1st visit (20-30 min), the participant receives all information about the study, is able to ask questions and visits the lab to become familiar with devices used during testing. On the 2nd visit (about 40 min), participants give their written consent for the study (after appropriate reflection time and before any procedure or collection of data relating to the study), complete questionnaires and undergo initial body measurements. On test days, upon arrival at the laboratory in the morning, participants are asked to empty their bladders if necessary, and to relax in a comfortable armchair. The monitoring equipment is then connected.
Participants undergo an oral glucose tolerance test, which involves drinking glucose dissolved in water and providing blood samples. Energy expenditure is measured before and after eating low and high protein test meals (two slices of toast and a milk-based drink to which protein powder, butter, and jam are added to adjust the protein content as necessary). On the day before the experiment, participants swallow a capsule sensor and energy expenditure measurements are undertaken the following morning (after an overnight fast of about 12 hours) to measure the energy cost of low-level physical activity. After about a 15 minute period of rest, the participant is connected to the equipment for resting energy expenditure monitoring for 30 minutes before and 60-90 minutes after a glass of cold water is drank over a 10-minute period. Finger skin temperature is measured by an infra-red camera before the cold water drink, and then every 15 minutes during 60-90 minutes afterward.

What are the possible benefits and risks of participating?
This study will help to find out why people born with low birth weight are more likely to develop obesity and cardiovascular diseases, and help to find accurate ways to identify those most at risk. Although this study is of no potential personal benefit to the participants, they will be provided with information on their body composition. In terms of risk, this study involves non-invasive techniques except for blood taking which may cause a small amount of pain, but which will be reduced by using well-trained staff (a medical doctor or a registered nurse) to collect the samples.

Where is the study run from?
University of Fribourg (Switzerland)

When is the study starting and how long is it expected to run for?
April 2017 to April 2020

Who is funding the study?
Swiss National Science Foundation (Switzerland)

Who is the main contact?
Prof. Abdul Dulloo

Trial website

Contact information

Type

Scientific

Primary contact

Prof Abdul Dulloo

ORCID ID

http://orcid.org/0000-0003-3877-6149

Contact details

University of Fribourg
Chemin du Musée 5
Fribourg
1700
Switzerland

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Phenotyping for thrifty metabolic traits in young adults born small: a risk factor for obesity and cardiometabolic diseases

Acronym

Study hypothesis

In young adults with low birth weight, thrifty metabolic traits may be expressed through one or more compartments of energy expenditure (EE) namely (i) in diminished glucose-induced thermogenesis, (ii) diminished dietary protein-induced thermogenesis, (iii) diminished energy cost of performing low-intensity physical activity, (iv) in a lower core body temperature.

Ethics approval

Commission cantonale (VD) d’éthique de la recherché sur l’être humain (CER-VD), 29/12/2017, ref: 2017-02087

Study design

Observational monocentric study

Primary study design

Observational

Secondary study design

Trial setting

Other

Trial type

Other

Patient information sheet

Condition

Obesity, diabetes, and heart disease

Intervention

Oral glucose tolerance test (OGTT) will be performed according to the guidelines provided by the American Diabetes Association (75 g glucose dissolved in 300 ml water; ingested within 5 minutes).

Low (11-12%) and high (24-25%) protein test meals will be provided. The test meal will consist of a simple breakfast meal base (two slices of toast and a milk-based drink to which protein powder, butter, and jam are added to adjust the protein content as necessary).

In the afternoon of the day preceding the experiment involving core temperature measurements, a capsule telemetric sensor will be ingested by the subject. Standardized energy expenditure measurements will be undertaken the following morning (after an overnight fast of ~12 h) using indirect calorimetry to measure energy cost of low-level physical activity. After about a 15 min period of rest, the subject is connected to the calorimetry system for resting energy expenditure monitoring for 30 min before and 60-90 min after a glass of cold water is ingested over a 10 min period. Finger skin temperature will be measured by an infra-red thermography camera prior to the cold water drink, and then every 15 min during 60-90 min post-drink period.

Intervention type

Other

Phase

Drug names

Primary outcome measure

The following measurements will be taken only once as this is an acute response study and does not involve any follow-up:
1. Energy expenditure (EE) in the pre- and post-prandial states, assessed at rest in a comfortably seated position by gas exchange (using indirect calorimetry) – measurements will be performed 30 min before and for 3 hours after the meal
2. EE in response to standardized low-intensity exercises measured by indirect calorimetry after 30 min of cycling on a bicycle ergometer and intermittent leg press over 40 min
3. Core body temperature measured by telemetry using ingested pill-sized sensors over 24 hours after sensor ingestion
4. Blood glucose and insulin measured during the oral glucose tolerance test after 30 min baseline and at 30, 60, 90, 120 min post-glucose drink (75 g glucose dissolved in 300 ml water); blood insulin will be measured by using an ELISA assay kit, whilst glucose will be measured by the reference method with hexokinase Glucose HK Gen 3

Secondary outcome measures

The following measurements will be taken only once as this is an acute response study and does not involve any follow-up:
1. Respiratory quotient, measured using indirect calorimetry as per EE above

Overall trial start date

01/04/2017

Overall trial end date

30/04/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Young men and women (18-35 years old)
2. Healthy (as determined from medical history)
3. Non-obese, body mass index (BMI) < 30kg/m2
4. Non-smokers
5. Birth weight in the range of 1.5 – 3.5 kg

Participant type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

30 for each group (total 60)

Participant exclusion criteria

1. Subjects born very premature defined as less than 28 weeks of gestation
2. Subjects who were treated for short stature (e.g. with growth hormone therapy)
3. Subjects taking medications that may alter body temperature, and any other condition that might impair the subject’s ability to participate in the study
4. Competition athletes, smokers, or overtly sedentary, or have eating disorders
5. Subjects who fear or have adverse reactions to cannulation
6. Subjects with a history of alcohol or any other drug abuse
7. Weight loss > 5% during 6 weeks prior to inclusion in the study
8. Pregnant and lactating women or females who desire to become pregnant over the study period (a pregnancy test is performed prior to each experimental protocol)
9. Subjects with gastro-intestinal complications, and fulfilling the official contraindications for the ingestion of the telemetry pill such as those diagnosed for diverticulitis, inflammatory bowel disease, gag reflex disorders or impairments, previous gastrointestinal surgery, hypo-motility of the gastrointestinal tract
10. Any person who might undergo magnetic resonance imaging (MRI) scanning while the telemetry pill is within the body, or having a cardiac pacemaker or another implanted electro-medical device

Recruitment start date

01/06/2018

Recruitment end date

31/12/2019

Locations

Countries of recruitment

Switzerland

Trial participating centre

Department of Endocrinology, Metabolism and Cardiovascular System
University of Fribourg Chemin du Musée 5
Fribourg
1700
Switzerland

Sponsor information

Organisation

Swiss National Science Foundation (SNSF)

Sponsor details

Wildhainweg 3
Bern
3001
Switzerland
-
div3@snf.ch

Sponsor type

Research council

Website

http://www.snf.ch/en/Pages/default.aspx

Funders

Funder type

Research council

Funder name

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Alternative name(s)

Swiss National Science Foundation, Fonds National Suisse de la Recherche Scientifique, Fondo Nazionale Svizzero per la Ricerca Scientifica, Fonds National Suisse, Fondo Nazionale Svizzero, Schweizerischer Nationalfonds, SNF, SNSF, FNS

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

Switzerland

Results and Publications

Publication and dissemination plan

Results are intended to be submitted to well-respected peer-reviewed journal for publication.

IPD sharing statement
The datasets generated during and/or analysed during the current study are not expected to be made available as the trialists will not have consent from the participants to share any of their data.

Intention to publish date

01/07/2020

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes