Effects of Intermittent Versus Continuous Energy Restriction on Metabolic Adaptation in Women With Obesity

Obesity Clinical Trial

— BREAK  

Official title:

Effects of Intermittent Versus Continuous Energy Restriction on Metabolic Adaptation in Women With Obesity

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05184361
• Other study ID #: BREAKSTUDY2021
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 13, 2022
• Est. completion date: June 2024

Study information

• Verified date: December 2023
• Source: Universidade do Porto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

One of the major challenges for treating obesity is to maintain a weight reduced state on the long term due to the high rate of weight regain. Therefore, the aim of this study is to evaluate the effects of an intermittent versus a continuous energy restriction in body composition (body weight, fat mass and fat-free mass) and metabolic adaptation, in women with obesity.

Description:

Literature is full of lifestyle interventions aimed for weight loss (WL) in several populations. However, one of the major challenges for treating obesity is WL maintenance on the long term due to the high rate of weight regain.

The reduction of the resting metabolic rate (RMR) is one of the identified aspects regarding compensatory metabolic alterations. After a WL intervention, decreases in RMR are mainly explained by the loss of fat-mass (FM) and fat-free mass (FFM). However, some authors showed that these reductions tend to be higher than predicted (explained by FM and FFM loss), a phenomenon called "metabolic adaptation" (MA). MA has been studied as a possible barrier to WL, WL maintenance and may contribute to weight regain. However, its relevance on long-term WM has been recently questioned. It is known that in order to lose weight, a negative energy balance (EB) must be achieved, meaning when EE surpasses the energy intake (EI). However, this negative EB may be achieved through several strategies, by changing the EI (energy restriction (ER)) and/or EE (increasing physical activity).

Regarding EI strategies, continuous energy restriction (CER) is the most common nutritional strategy for WL, consisting in a daily energy restriction according to one's specific needs. However, some concern has been pointed out regarding this widely used strategy, once it evolves several behavioural, metabolic and endocrine responses that may contribute to therapeutic adherence, undermining WL and its maintenance. On the other hand, intermittent energy restriction (IER) has been recently suggested as an alternative to CER. IER consists in interspersing periods of ER with periods of neutral EB, called "refeed" or "diet breaks" during the WL phase. Energy restriction is followed by several adaptive responses, namely endocrine, including thyroid, appetite regulation and steroid hormones, influencing the energy expenditure (EE), body composition and satiety. Therefore, understanding how hormones may influence RMR and as a consequence, AT, it´s crucial to a better understanding.

According to the literature, compensatory metabolic responses following ER and WL can be reversed following a 7-to-14-day period of energy balance post-weight loss. Therefore, considering that the length of the nutritional intervention for WL may benefit a reduction, we consider relevant to study other ER designs/patterns, namely 2 weeks in ER interspersed with 1 week in EB, comparing to a CER. Taking into account this therapeutic as a potential opportunity for the obesity's treatment, this paper describes the protocol for a randomized controlled trial (RCT), which targets to evaluate the effects of an IER (alternating 2 weeks of ER with 1 in neutral EB), comparing to a CER. This trial aims: a) to compare the effects of a IER vs CER strategy on body composition variables (body weight, fat mass and fat-free mass) and in metabolic adaptation and, b) to understand if participants will be able to maintain a reduced weight state after 12 months (successful weight-loss maintenance), in both groups.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 74
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 45 Years

Eligibility

Inclusion Criteria:

• Women

• BMI ranging between 30 and 39.9 kg/m2

• Age between 20-45 years

• Weight stable in the last 6 months (less than 5% weigh variation)

• Inactive (less then 150 min/week of moderate physical activity or 75 min/week of vigorous physical activity

• Living in Lisbon Metropolitan Area and being able to drive to Faculty of Human Kinetics and Germano de Sousa Laboratory (Algés)

• Available to be randomized to any of the trial groups (CER or IER)

• Willing to commit with the assigned group protocol, including the nutritional intervention and lifestyle recommendations, as well as being available for participation in all evaluation moments.

Exclusion Criteria:

• Previous or present health disorders: cancer, autoimmune, cardiac, psychiatric, kidney and liver disease (except liver steatosis), diabetes, chronic intestinal inflammatory disease, or other medical conditions known to affect energy balance homeostasis

• Menopause

• Hormonal or thyroid disorder

• Medications that promote weight gain or alter energy balance, including corticosteroids, antidepressants, anxiolytics, mood-stabilizing, and antipsychotics

• Medications or dietary supplements for weight-loss in the past 3 months

• Pregnant for the past 6 months or breastfeeding

• Planning to get pregnant in the next 2 years or getting pregnant during the study

• Current consumption of more than 14 alcoholic drinks per week or other substance abuse, and/or current acute treatment or rehabilitation program for alcohol/substance abuse

• Surgery or in hospital admission for the last month

• Positive for Covid-19 in the past 3 months or testing positive during the intervention phase of the study

Related Conditions & MeSH terms

• Obesity
• Weight Loss

Intervention

Behavioral:
• Intermittent energy restriction (IER)
Both groups will be accompanied by a registered dietitian in order to provide an individual and personalized diet plan that will suppress the respective daily requirements for each phase. Macronutrient distribution will be the following: 35% protein, 35% carbohydrate and 30% fat. Daily energy requirements (DER) will be calculated by multiplying measured RMR (through indirect calorimetry) by physical activity level (PAL), assessed by accelerometry. In order to achieve a neutral EB, 100% of their daily energy requirements (DER) will be prescribed for each participant. For both groups, an energy restriction of 33% of one's DER will be created. The IER group will alternate between 2-weeks in energy restriction (67% DER) and 1-week in neutral EB (100% DER), in a total of 23-weeks. The IER group will alternate between 2-weeks in energy restriction (67% DER) and 1-week in neutral EB (100% DER), in a total of 23-weeks.
• Continuous energy restriction (CER)
A dietary plan comprising 67% of DER will be prescribed to the CER group. Participants will be asked to follow this plan in a total of 16-weeks, without interruptions.

Locations

Country	Name	City	State
Portugal	Faculdade de Motricidade Humana da Universidade de Lisboa	Cruz Quebrada	Lisbon

Sponsors (2)

Lead Sponsor	Collaborator
Universidade do Porto	University of Lisbon

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fat mass	To estimate total fat mass (FM), dual energy X-ray absorptiometry (Hologic Explorer-W, Waltham, USA) will be used. A whole-body scan will be performed and the attenuation of X-rays pulsed between 70 and 140 kV synchronously with the line frequency for each pixel of the scanned image will be measured.	24 months
Primary	Adaptive thermogenesis (AT)	AT will be assessed as: AT (kcal/d) = (pREE at the end of the intervention - mREE at the end of the intervention) - (pREE baseline - mREE baseline)	24 months
Secondary	Weight	Weight will be determined using a digital scale, with 0,1 kg interval (Seca, Hamburg, Germany).	24 months
Secondary	Height	Height will be determined using a stadiometer Seca 704 s, with 0,1 cm intervals (Seca, Hamburg, Germany)	Baseline
Secondary	Body mass index (BMI)	BMI will be calculated using the formula [weight (kg)/height2(m2)]	24 months
Secondary	Fat-free mass (FFM)	To estimate fat-free mass (FFM), dual energy X-ray absorptiometry (Hologic Explorer-W, Waltham, USA) will be used. A whole-body scan will be performed and the attenuation of X-rays pulsed between 70 and 140 kV synchronously with the line frequency for each pixel of the scanned image will be measured.	24 months
Secondary	Resting energy expenditure (REE)	REE will be determined using indirect calorimetry COSMED Fitmate device (Cosmed, Rome, Italy) will be used to measure breath-by-breath oxygen consumption (V?O2 ) and carbon dioxide production (V?CO2) using a facial mask.	24 months
Secondary	Energy balance (EB)	The EB will be calculated as: EB (kcal/d) = 1.0 * (?FMM/?t) + 9.5 * (?FM/?t). ?FM and ?FFM represent the change in grams of FM and FFM from the beginning to end of the intervention and ?t is the time length of the intervention in days.	24 months
Secondary	Free-living physical activity	The amount of activity assessed by the Actigraph accelerometer will be expressed as minutes per day spent in different intensities. The cutoff values used to define the intensity of PA and therefore to quantify the mean time in each intensity (sedentary, light, moderate or vigorous) will be: sedentary: < 100 counts·min-1; light: 100-2019 counts·min-1; moderate: 2020-5998 counts·min-1 (corresponding to 3-5.9 METs); vigorous: = 5999 counts·min-1 (corresponding to =6 METs). A valid day will be defined as having 600 or more minutes (=10h) of monitor wear during waking hours.	24 months
Secondary	Total daily energy expenditure (TDEE)	TDEE will be assessed by the Actigraph accelerometer using the Crouter et al equations.	24 months
Secondary	Physical activity energy expenditure (PAEE)	PAEE will be calculated as total energy expenditure (TEE) minus (0.1*TEE + REE), assuming the thermic effect of food represents 10% of TEE, and REE represents Resting energy expenditure.	24 months
Secondary	Blood thyroid levels	Free T3 and free T4 will be run by immunoassay with chemiluminescent detection (Advia Centaur, Siemens).	24 months
Secondary	Blood insulin levels	Blood insulin levels assessment will be performed in an automated analyser with chemiluminescent detection [Advia Centaur, Siemens].	24 months
Secondary	Blood leptin levels	Serum levels of leptin will be measured by enzyme immunoassay [ELISA].	24 months
Secondary	Blood cortisol levels	Blood levels of cortisol will be determined by immunoassay with chemiluminescence detection [Advia Centaur, Siemens].	24 months