- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04773132
Human Metabolic Flexibility: Its Role in Energy Regulation and Obesity
February 23, 2021 updated by: JeyaKumar Henry, Clinical Nutrition Research Centre, Singapore
Obesity is commonly described as a consequence of excess calorie intake.
Conventionally, the physiological variables that have been of extensive interest are food intake and energy expenditure.
Despite decades of research on factors influencing intake and expenditure, to date, no compelling theory has been promulgated to explain why certain humans are more susceptible to weight gain than others.
The investigators hypothesize that the measure of an individual's fraction of energy mobilized or deposited as protein (P-ratio), contributes towards an obese morphology and may essentially form a novel approach in understanding the etiology, management and treatment of obesity.
In addition, there is a general perception that the consumption of sugar sweetened foods and beverages are one of the major causes of obesity.
This study aims to understand metabolic flexibility and the glycemic index of diets in the etiology of obesity.
Individual metabolic flexibility may be the key factor that predisposes an individual to obesity.
This study is carried out to determine the P-ratio in human subjects.
Study Overview
Detailed Description
Obesity is commonly described as a consequence of excess calorie intake.
Conventionally, the physiological variables that have been of extensive interest are food intake and energy expenditure.
Despite decades of research on factors influencing intake and expenditure, to date, no compelling theory has been promulgated to explain why certain humans are more susceptible to weight gain than others.
The investigators believe that a measure of an individual's metabolic flexibility towards an obese morphology is essential and forms a novel approach in understanding the etiology, management and treatment of obesity.
Payne and Dugdale developed a simple model of energy balance, based on dividing the human body into four compartments, namely "fast" lean tissue (protein), "slow" lean tissue (protein), structural fat, and tissue fat.
Notionally, these are considered to act as four separate compartments which interconnect with each other.
Body weight is thus simply the sum of the four weights, and metabolic rate is the sum of the separate compartment rates.
Any energy deficit in the "balancing compartment" is met by withdrawing tissues from the neighboring fat and lean (muscle) compartments in a proportion which is fixed for any individual.
The observed human variability in both the susceptibility to gain weight or to lose weight efficiently on a calorie surplus or restricted diet is thus afforded by using the model developed by Payne and Dugdale for energy balance.
P-ratio is calculated on the assumption that body protein is 16% nitrogen and has a metabolizable energy value of 16.7 kJ/g.
Thus P-ratio can be calculated as: P- ratio= urinary nitrogen excretion x 6.25 x 16.7 / total energy expenditure.
The regulatory control of energy-partitioning between protein and fat is highly variable between individuals, but constant within the same subject.
It is this variability in tissue partitioning between lean (protein) and fat that is central to the regulation of body weight.
This implies that for a given individual, there is a fixed partitioning of energy between lean (protein) and fat tissue when excess calories are consumed.
Using the results of the classical study of human semi-starvation by Keys et al, Dugdale and Payne calculated the individual pattern of tissue mobilization (P-ratio) in these subjects.
The P-ratio ranged from 0.03 to 0.60.
On the basis of these data, they classified individuals into "metabolically lean" and "metabolically fat".
A P-ratio of 0.03 means approximately 3% of the energy loss from this subject's body tissues was derived from protein catabolism and 97% from fat.
Thus during excess calorie consumption, 3% of the calories will be deposited as protein and 97% as fat ("metabolically fat").
Similarly a subject with a P-ratio of 0.60 will deposit 60% calories as protein and only 40% as fat ("metabolically lean").
This stratification of "metabolic type" is a novel approach in obesity research, treatment and its management.
The current method for the determination of P-ratio is based on subjects undergoing total starvation/fasting, e.g.
complete food restriction, ad libitum water intake.
This is a highly impractical approach.
The investigator's proposal is to develop a more convenient and practical methodology to determine the P-ratio.
An individual's Basal Metabolic Rate after a 10 hour overnight fast will approximate the denominator of the P-ratio.
Henry et al reported a quantitative relationship between a fasting urine nitrogen loss (FUNL) and obligatory urinary nitrogen loss (OUNL), the ratio FUNL: OUNL remained close to 1.5.
OUNL can be measured in urine when a subject is fed a protein free diet.
With these two measures, the P-ratio of an individual can be estimated.
OUNL is the protein lost in the urine when fed a zero or non-protein diet and fasting urinary loss is the nitrogen lost during starvation/ fasting (FUNL).
The investigator's proposed study will be the first real-time study that will utilize the obligatory urine nitrogen loss and BMR to quantitate human P-ratio.
Study Type
Interventional
Enrollment (Actual)
68
Phase
- 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 Locations
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-
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Singapore, Singapore, 117599
- Clinical Nutrition Research Centre
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-
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
Ages Eligible for Study
21 years to 35 years (ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Chinese Male or Female
- Age between 21-35 years
- Body mass index 17.5-32.0 kg/m2
Exclusion Criteria:
- People with major chronic disease such as heart disease, cancer or diabetes mellitus
- People with family history of diabetes
- People who have intolerances or allergies to study foods
- Individuals who are taking drugs known to affect glucose metabolism, body fat distribution, appetite, food intake or energy metabolism
- Individuals who are on a special diet or recently on a weight-lost diet
- Pregnant women
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: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Low Protein Diet
All subjects will be given a low protein/protein-free diet in order to deplete the label protein pool.
The diet provided will meet the daily energy requirements of all the subjects.
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Low protein/protein-free diet for 3 days (Day 1, 2 and Day 3) in order to deplete the label protein pool.
The diet provided will meet the daily energy requirements of all the subjects.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Weight
Time Frame: Day 1
|
Kg
|
Day 1
|
Waist Circumference
Time Frame: Day 1
|
cm
|
Day 1
|
Hip Circumference
Time Frame: Day 1
|
cm
|
Day 1
|
Body fat
Time Frame: Day 1
|
Percentage
|
Day 1
|
Estimated visceral adipose tissue area
Time Frame: Day 1
|
cm2
|
Day 1
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Height
Time Frame: Day 1
|
cm
|
Day 1
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
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)
May 19, 2015
Primary Completion (ACTUAL)
April 1, 2016
Study Completion (ACTUAL)
December 11, 2017
Study Registration Dates
First Submitted
February 18, 2021
First Submitted That Met QC Criteria
February 23, 2021
First Posted (ACTUAL)
February 26, 2021
Study Record Updates
Last Update Posted (ACTUAL)
February 26, 2021
Last Update Submitted That Met QC Criteria
February 23, 2021
Last Verified
February 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2014/01182
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
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.
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