Clinical trial NCT03638895: Energy Expenditure From ECAL Indirect Calorimeter in a Multicomponent Weight Management Service
Official title: Randomised Controlled Trial to Evaluate Impact of Energy Expenditure Information on the Outcome of Weight Loss During a Standardised Multicomponent Weight Management Intervention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Severe Obesity
Sleep Apnoea
Keywords: weight management
obesity
severe obesity
structured dietary intervention
calorie restriction
indirect calorimetry
resting energy expenditure
resting metabolic rate
respiratory quotient
substrate oxidation
glycemic variability
insulin sensitivity
peripheral neuropathy
Lead sponsor: University of Liverpool
Sponsor class: OTHER
Collaborators: name: Metabolic Health Solutions UK
First posted: 2018-08-20
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel assignment
Primary purpose: TREATMENT

Brief summary: Whether greater weight loss is as a result of a smaller reduction in energy expenditure with caloric restriction is not known. Resting energy expenditure and 24-hour energy expenditure vary substantially between individuals. In some cases, relatively reduced rates of 24h EE predict weight gain in some populations who have high prevalence of obesity. Obese individuals that lose weight experience a decrease in 24-h EE and resting energy expenditure that is lower than predicted based on changes in body composition. Most weight loss studies have found a large individual variation in the amount of weight change, and whether an individual's response to an intervention can be predicted is not clear. Measurements of 24-hour EE in response to fasting may help predict weight loss. The ECAL indirect calorimeter (ECAL) is a validated device purpose-built to provide the practitioner and patient with energy information that allows for more accurate, reliable method of establishing an obese individuals' metabolic profile. The aim of this study is to determine whether providing energy information from ECAL indirect calorimeter as an adjunct to the multicomponent weight management intervention in non-diabetic obese and severely obese individuals would help predict the response of weight loss.

Detailed description: Weight loss is important to improve overall health and reduce risk of obesity-related comorbidities such as diabetes. Numerous studies performed on individuals with predisposed genetic propensity to obesity who are deemed to be metabolically 'thrifty', require further structured intensification of caloric restriction and change in physical activity in order to achieve weight loss. Whether greater weight loss is as a result of smaller reduction in energy expenditure with calorie restriction is not known. Resting energy expenditure and 24-hour energy expenditure vary substantially between individuals. Obese individuals that lose weight experience a decrease in 24-h EE and resting energy expenditure that is lower than predicted based on changes in body composition. Most weight loss studies have found a large individual variation in the amount of weight change, and whether an individual's response to an intervention can be predicted is not clear. Measurements of 24-hour EE in response to fasting may help predict weight loss. The ECAL indirect calorimeter (ECAL) is a validated device purpose-built to provide the practitioner and patient with energy information that allows for more accurate, reliable method of establishing an obese individuals' metabolic profile. The ECAL device also measures the respiratory quotient (RQ) which is the ratio of the volume of carbon dioxide expired to that of oxygen consumed by the individual for every breath. Previous studies demonstrated variability in role of RQ in predicting weight loss, but individuals who demonstrated an RQ in the lower range (\<0.72) were more likely to maintain the weight-loss achieved on a caloric restriction and avoid a weight loss rebound as compared to those with RQ in the higher range (\>0.75). This suggests that RQ could prove useful in clinical practice as a prognostic marker for long-term effectiveness of low- and very-low-calorie diets used to induce weight loss. Baltimore Longitudinal Study on Aging shared a similar finding that fasting RQ or respiratory exchange ratio adjusted for age, BMI, and fat free mass was positively related to weight change. The aim of this study is to determine whether providing energy information from ECAL indirect calorimeter as an adjunct to the multicomponent weight management intervention in non-diabetic obese and severely obese individuals would help predict the response of weight loss.

Eligibility criteria: Inclusion Criteria:

* BMI \> or equivalent to 30 kg/m2 to - 60 kg/m2
* Stable weight (change of \<5% within 12 weeks before screening based on medical history)
* Subjects are well-motivated, capable and willing to learn how to undergo indirect calorimetry testing
* Willing and able to adhere to prohibitions and restrictions specified within this protocol

For Subjects participating in the glycaemic variability sub-study:

* Subject understands instructions on the use of continuous glucose monitor sensor and is willing to undergo appropriate training and testing

Exclusion Criteria:

* Taking weight loss medication within 12 weeks prior to randomisation
* Previous or planned bariatric surgery
* History of Type 1, Type 2 diabetes mellitus, DKA or diabetes secondary to pancreatitis
* Has HbA1c \> or equal to 6.5% or Fasting Plasma Glucose \> or equal to 7.0 mmol/L at screening.

NOTE: a one-time repeat measurement is allowed, if value of HbA1c and/or FPG is not consistent with prior values

* History of obesity with a known secondary cause (Cushing's disease/syndrome)
* Oral corticosteroid use (except in the short term use of a 7-10 day course)
* Ongoing, inadequately controlled thyroid disorder defined as thyroid-stimulating hormone \> 6 mIU/litre or \< 0.4 mIU/litre
* History of malignancy within 3 years before screening (or diagnosis of malignancy within this period)
* estimated glomerular filtration rate \< 30 ml/min/1.73m2 on serum testing
* Alanine aminotransferase level is \<2.0 times the upper limit of normal or total bilirubin is \>1.5 times the upper limit of normal at screening
* Other major illness likely to preclude participation in the trial
* History of glucagonoma
* A myocardial infarction, unstable angina, revascularisation procedure (stent or bypass graft surgery) or cerebrovascular accident within 12 weeks before screening

Primary outcomes:
measure: Magnitude of weight loss (in kg)
timeFrame: 6 months
Secondary outcomes:
measure: Resting metabolic rate (RMR)
timeFrame: 6 months
measure: Respiratory Quotient (RQ)
timeFrame: 6 months
measure: Secretion of gut hormones (GLP-1, GIP, PYY)
timeFrame: 6 months
measure: Glycaemic variability
timeFrame: 6 months
measure: Insulin sensitivity
timeFrame: 6 months
measure: Sensory Neuropathy Testing in Prediabetic Obese Individuals
timeFrame: 6 months
measure: Douleur Neuropathique en4 Questions (DN4)
timeFrame: 6 months
measure: Visual analogue score
timeFrame: 6 months
measure: modified Total Neuropathy Score
timeFrame: 6 months
measure: Brief Pain Inventory Short Form
timeFrame: 6 months
Other outcomes:
Locations:
city: Liverpool
country: United Kingdom
facility: University Hospital Aintree
Study officials:
affiliation: University of Liverpool
name: John Wilding, DM FRCP
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Melo CM, Tirapegui J, Ribeiro SM. [Human energetic expenditure: concepts, assessment methods and relationship to obesity]. Arq Bras Endocrinol Metabol. 2008 Apr;52(3):452-64. doi: 10.1590/s0004-27302008000300005. Portuguese.
citation: Lam YY, Ravussin E. Indirect calorimetry: an indispensable tool to understand and predict obesity. Eur J Clin Nutr. 2017 Mar;71(3):318-322. doi: 10.1038/ejcn.2016.220. Epub 2016 Nov 16.
citation: McLay-Cooke RT, Gray AR, Jones LM, Taylor RW, Skidmore PML, Brown RC. Prediction Equations Overestimate the Energy Requirements More for Obesity-Susceptible Individuals. Nutrients. 2017 Sep 13;9(9):1012. doi: 10.3390/nu9091012.
citation: Alves VG, da Rocha EE, Gonzalez MC, da Fonseca RB, Silva MH, Chiesa CA. Assessement of resting energy expenditure of obese patients: comparison of indirect calorimetry with formulae. Clin Nutr. 2009 Jun;28(3):299-304. doi: 10.1016/j.clnu.2009.03.011. Epub 2009 Apr 23.
citation: Lim J, Alam U, Cuthbertson D, Wilding J. Design of a randomised controlled trial: does indirect calorimetry energy information influence weight loss in obesity? BMJ Open. 2021 Mar 24;11(3):e044519. doi: 10.1136/bmjopen-2020-044519.