Menopause Related ConditionsNCT05912309
Effects of Time-restricted Eating and Exercise Training on Skeletal Muscle Mass Quantity, Quality and Function in Postmenopausal Women With Overweight and Obesity
A study testing Time Restricted Eating (TRE), Exercise and Caloric Restriction in people with Menopause Related Conditions and Sarcopenia, run by Idoia Labayen at 1 site in Spain.
Trial summary
The goal of this randomized controlled trial] is to investigate the effects of a 12-week time restricted eating (TRE) and exercise combined intervention, as compared to (i) TRE alone, and to (ii) Caloric Restriction (CR) plus the same exercise intervention elicited by the TRE group, on Skeletal muscle tissue (SMT)… Read more about this study
- Who is it for?
- Ages 50 to 65 years, women only
- Conditions the study is for
- Menopause Related Conditions, Sarcopenia, Osteoporosis Postmenopausal
- What is being tested?
- Time Restricted Eating (TRE), Exercise and Caloric Restriction
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteSpain
- Study dates
- 1 Sep 2023to Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 50 and 65 years.
- Menopause (Phase +1a)
- Body mass index ≥25.0 and <40 kg/m2 or waist circumference > 94 cm.
- Weight stability (within 3% of screening weight) for >3 months prior to baseline.
- Sedentary lifestyle (<150 min/week of moderate-vigorous intensity exercise) for >3 months prior to baseline.
- Usual feeding window ≥12 hours.
Who cannot join
- History of major adverse cardiovascular events, clinically significant renal, endocrine or neurological disease, bariatric surgery, HIV/AIDS, known inflammatory and/or rheumatologic disease, cancer or other medical condition in which fasting or exercise is contraindicated.
- Use of exogenous (sex) hormones (hormone replacement therapy).
- Type 1 or type 2 diabetes.
- Severe psychiatric disorders, eating disorders, sleep disorders or alcohol abuse.
- Regular use of medications or compounds that may affect study results.
- Participating in a weight loss or weight control program.
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- Caregiver of a dependent person who requires frequent nighttime care/sleep interruptions. Shift workers with variable schedules (e.g., nighttime). Frequent travel across time zones during the study period.
- Fear of needles and claustrophobia of magnetic resonance imaging (MRI).
- Any medical situation that prevents the performance of MRI (pacemakers, prostheses, etc).
- Being unable to understand and accept the instructions or the objectives and protocol of the study.
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Universidad Pública de Navarra
Pamplona, Navarre, 31006
Idoia Labayen, PhD, idoia.labayen@unavarra.es
About this study
The goal of this randomized controlled trial] is to investigate the effects of a 12-week time restricted eating (TRE) and exercise combined intervention, as compared to (i) TRE alone, and to (ii) Caloric Restriction (CR) plus the same exercise intervention elicited by the TRE group, on Skeletal muscle tissue (SMT) quantity, quality and function (primary outcome), Resting energy expenditure (REE) and cardiometabolic health (secondary outcomes), and miRNA biomarkers in postmenopausal women with overweight or obesity.
Read the detailed description
Time restricted eating (TRE) may be a potential lifestyle tool for the management of obesity in populations at risk of sarcopenia. However, weight loss may occur at the expense of lean mass, thus producing an undesirable reduction of Skeletal Muscle Tissue (SMT). To date, studies focused on body composition suffer from methodological shortcomings in adequate SMT quantity and quality measurement (e.g. using gold standard magnetic resonance imaging, MRI) and function, dietary intake protein counselling and the monitoring of dietary energy and macronutrient intake. Importantly, no TRE studies have been conducted in postmenopausal women with overweight who are at high risk of sarcopenia. Studies such as the one presented herein are needed to elucidate the effects of TRE on SMT and protein balance in the middle- and long-term lifestyle intervention. In addition, the potentially myoprotective roles of dietary protein and exercise need to be more cogently established within the framework of a TRE regime in populations at risk of sarcopenia. Further, the effects of TRE+exercise on SMT quantity, quality and function should be compared to currently accepted lifestyle therapy lifestyle therapy for obesity management in adults at high risk of sarcopenia (Caloric Restriction (CR) + exercise and adequate protein intake). Finally, the underlying mechanisms of SMT quantity, quality and function loss, as well as those explaining the effects of TRE and exercise are unknown. The investigators will explore circulating miRNA profiles as novel, non-invasive and feasible prognostic biomarkers of changes in SMT quantity, quality and function.
- This study will be the first randomized controlled trial to investigate whether the addition of exercise to TRE is able to reverse the SMT loss induced by the TRE alone, and if the combination of TRE and exercise confers any additional benefits on SMT quantity, quality and function above the currently recommended lifestyle intervention.
- The few previous TRE studies examined changes in body composition using dual-energy X-ray absorptiometry (DXA); however, this is not the most appropriate method to assess SMT and it does not evaluate IMAT. The investigators will use magnetic resonance imaging (MRI) scanning (gold standard) to measure changes in SMT and intra-muscular adipose tissue (IMAT, muscle quality).
- There is a lack of knowledge on the effects of TRE on muscle strength. This important determinant of sarcopenia will be assessed with gold standard methodology.
- This study will be pioneer at quantifying the long-term adherence and the persistence of the effects of TRE and exercise on SMT quantity, IMAT and function (12 months)
- Importantly, the investigators will be able to study miRNA predictors of changes in SMT quantity, IMAT and function in postmenopausal women.
- Available studies on TRE, although enlightening, have solely assessed acute or short-term (<2 weeks) effects of TRE on Resting Energy Expenditure (REE). It will be evaluated whether TRE and exercise confers any additional advantage on REE maintenance above the currently recommended lifestyle intervention in the middle and long-term.
- The majority of TRE studies were focused on body weight or total adiposity. The present study will also evaluate the effects of the intervention on specific ectopic fat depots strongly associated with cardiometabolic health, morbidity and mortality using MRI (i.e., visceral adipose tissue (VAT) and liver fat), in the middle- (12 weeks) and long-term (12 months).
- Impaired systemic glucose homeostasis is common in postmenopausal women with overweight. TRE and exercise intervention has the potential of reducing Insulin Resistance (IR); therefore, the present project will include the measurement of continuous glucose monitoring (CGM) analyzing day-to-day glucose homeostasis.
- Exercise reduces the risk of sarcopenic obesity and ectopic fat aggregation, improves cardiometabolic health and reduces proinflammatory markers, but the underlying mechanisms are largely unknown. The analysis of circulating miRNA profiles can help to elucidate the mechanisms explaining the response to the lifestyle intervention as well as identifying potential therapeutic targets.
- There is a high inter-individual variability in the response to TRE and exercise interventions, but its predictors are unknown. This study will focus on miRNAs as potential predictive and prognostic biomarkers.
- Gender dimension: women are under-represented in TRE studies and there is no previous study conducted on postmenopausal women. Studies on this specific population are of great interest for several reasons: unique hormonal status that confers elevated risk of obesity and obesity-related morbidities, high risk of sarcopenia, and an enormous interest on self-administered TRE that could entail unknown health consequences.
Participants: Postmenopausal women (n=78) with an absence of menses for over two years (at least stage +1a) and with overweight (BMI>25 kg/m2) or obesity (BMI>30 kg/m2 and BMI<=40 kg/m2) will be recruited at the Endocrinology Unit of the University Hospital of Navarra.
Intervention: Participants will be randomly allocated 1:1:1 to (1) CR+exercise, (2) TRE, and (3) TRE+exercise groups. Before baseline measurements and group allocation, there will be a 2-week lead-in period where the eating window, glucose and physical activity will be continuously monitored. Thereafter, participants will follow the 12-week intervention according to their allocated group.
- CR+exercise group: Individualized intensive behavioral intervention weight loss program including CR, exercise training and lifestyle education designed according to the current guidelines. CR will be tailored to participants (objectively assessed). Diet will provide 600 kcal/day less than the individual energy requirements based on measured REE (indirect calorimetry) and multiplied by an activity factor obtained by accelerometry. Experienced nutritionists will design personalized and balanced CR diet, and will train the participants through the food exchange system to follow the treatment. In those cases in which the CR compromised a protein intake of at least 1.2 g/kg/day, the macronutrient percentage distribution will be modified prioritizing achieving this minimum protein intake. Sport sciences specialist will design, supervise and monitor the concurrent exercise intervention following the 2020 WHO recommendations. The program will be tailored to the participant ́s ability and health, and will be focused on a gradual increase to levels that are safe. Resistance training: 2-3 times/week designed to manage, attenuate and even prevent the loss of SMT and function.
- TRE group: Participants will be required to reduce their eating time window to ≤ 8 hours/day. Women can choose when to begin eating, but the last meal should be completed before or at 20:00 hours (concentrating the eating window towards the active phase confers higher cardiometabolic health benefits). Our preliminary results suggest that this eating window is feasible and safe.
- TRE+exercise group: This group will combine the intervention of the TRE group and the same exercise intervention of the CR+exercise group. The exercise sessions will be scheduled within or immediately after their eating window in order to maximize MPS. Morning and afternoon training schedules will be offered to participants.
The three groups will receive dietary advice regarding the daily amount of high quality protein and meal-specific protein quantities. All the participants will attend a lifestyle education program based on Mediterranean diet and WHO physical activity recommendations every two weeks.
Long-term follow-up: Weight cycling is frequent in women and is associated with increased morbidity. There are no previous studies examining the persistence of the effects of TRE+exercise in the long-term. Also, it seems that the adherence to the TRE regime is higher than to the CR, but the evidence is scarce. This project will assess the main study outcomes and the adherence in order to examine the persistence and feasibility of the intervention effects 12 months after the cessation.
- Being tested
- Time Restricted Eating (TRE), Exercise, Caloric Restriction
- Keywords
- Obesity, Overweight, Sarcopenia, Menopause, Exercise, Resistance Exercise, Physical activity, intramuscular adipose tissue, Visceral adipose tissue, Liver fat, Skeletal muscle mass, Muscle function, Muscle quality, Osteoporosis
- Medical subject headings
- Sarcopenia, Osteoporosis, Postmenopausal, Obesity, Overweight, Motor Activity, Fatty Liver, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Time Restricted Eating (TRE)Behavioural
Participants will be required to reduce their eating time window to ≤ 8 hours/day. Women can choose when to begin eating, but the last meal should be completed before or at 20:00 hours (concentrating the eating window towards the active phase confers higher cardiometabolic health benefits). Our preliminary results suggest that this eating window is feasible and safe. Participants will receive dietary advice regarding the daily amount of high quality protein and meal-specific protein quantities. All the participants will attend a lifestyle education program based on Mediterranean diet and WHO physical activity recommendations every two weeks.
ExerciseBehavioural
Sport sciences specialists will design, supervise and monitor the concurrent exercise intervention following the 2020 WHO recommendations. The program will be tailored to the participant's ability and health, and will be focused on a gradual increase to levels that are safe. Resistance training: 3 times/week designed to manage, attenuate and even prevent the loss of skeletal muscle tissue and function. The exercise sessions will be scheduled within or immediately after their eating window in order to maximize muscular muscle protein synthesis. Morning and afternoon training schedules will be offered to participants.
Caloric RestrictionBehavioural
Individualised intensive behavioural intervention weight loss program including CR, exercise training and lifestyle education designed according to the current guidelines. CR will be tailored to participants (objectively assessed). Diet will provide 600 kcal/day less than the individual energy requirements based on measured resting energy expenditure (indirect calorimetry) and multiplied by an activity factor obtained by accelerometry. Experienced nutritionists will design personalized and balanced CR diet, and will train the participants through the food exchange system to follow the treatment. In those cases in which the CR compromised a protein intake of at least 1.2 g/kg/day, the macronutrient percentage distribution will be modified prioritizing achieving this minimum protein intake.
| Study group | Role | What they receive |
|---|---|---|
| Time Restricted Eating (TRE) | Experimental | Not described Receives: Behavioral: Time Restricted Eating (TRE) |
| Time Restricted Eating (TRE) + Exercise | Experimental | Not described Receives: Behavioral: Time Restricted Eating (TRE); Behavioral: Exercise |
| Caloric restriction (CR) + Exercise | Active comparator | Not described Receives: Behavioral: Exercise; Behavioral: Caloric Restriction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Skeletal muscle tissue quantity - Baseline
Skeletal muscle tissue (Cross sectional area (cm2) and Volume (cm3)) will be quantified by magnetic resonance imaging ((MRI) Magnetom Vida 3T system, Siemens, Healthineers), the gold standard methodology, at the most representative sites: mid-thigh, psoas (L3) and paraspinal and abdominal wall (L2-L4). Both Detailed information about imaging segmentation and processing can be found in previous work of our group. The segmentation for all these structures will be done with a semiautomatic proprietary algorithm developed in our group.
Measured: Just after the end of the 12-week intervention (+1 to +3 days)
Skeletal muscle tissue quantity - 12 weeks
Skeletal muscle tissue (Cross sectional area (cm2) and Volume (cm3)) will be quantified by magnetic resonance imaging ((MRI) Magnetom Vida 3T system, Siemens, Healthineers), the gold standard methodology, at the most representative sites: mid-thigh, psoas (L3) and paraspinal and abdominal wall (L2-L4). Both Detailed information about imaging segmentation and processing can be found in previous work of our group. The segmentation for all these structures will be done with a semiautomatic proprietary algorithm developed in our group.
Measured: Just before the start of the 12-week intervention (-3 to -1 days), just after the end of the 12-week intervention (+1 to +3 days) and 1 year after the end of the intervention
Skeletal muscle tissue quantity - 1 year
Skeletal muscle tissue (Cross sectional area (cm2) and Volume (cm3)) will be quantified by magnetic resonance imaging ((MRI) Magnetom Vida 3T system, Siemens, Healthineers), the gold standard methodology, at the most representative sites: mid-thigh, psoas (L3) and paraspinal and abdominal wall (L2-L4). Both Detailed information about imaging segmentation and processing can be found in previous work of our group. The segmentation for all these structures will be done with a semiautomatic proprietary algorithm developed in our group.
Measured: 1 year after the end of the intervention
Skeletal muscle tissue quality - Baseline
Intermuscular and Intramuscular adipose tissue (fat fraction(%)) will be quantified by magnetic resonance imaging ((MRI) Magnetom Vida 3T system, Siemens, Healthineers), the gold standard methodology, at the most representative sites: mid-thigh, psoas (L3) and paraspinal and abdominal wall (L2-L4). Both Detailed information about imaging segmentation and processing can be found in previous work of our group. The segmentation for all these structures will be done with a semiautomatic proprietary algorithm developed in our group.
Measured: Just before the start of the 12-week intervention (-3 to -1 days)
Skeletal muscle tissue quality - 12 weeks
Intermuscular and Intramuscular adipose tissue (fat fraction(%)) will be quantified by magnetic resonance imaging ((MRI) Magnetom Vida 3T system, Siemens, Healthineers), the gold standard methodology, at the most representative sites: mid-thigh, psoas (L3) and paraspinal and abdominal wall (L2-L4). Both Detailed information about imaging segmentation and processing can be found in previous work of our group. The segmentation for all these structures will be done with a semiautomatic proprietary algorithm developed in our group.
Measured: Just after the end of the 12-week intervention (+1 to +3 days)
Skeletal muscle tissue quality - 1 Year
Intermuscular and Intramuscular adipose tissue (fat fraction(%)) will be quantified by magnetic resonance imaging ((MRI) Magnetom Vida 3T system, Siemens, Healthineers), the gold standard methodology, at the most representative sites: mid-thigh, psoas (L3) and paraspinal and abdominal wall (L2-L4). Both Detailed information about imaging segmentation and processing can be found in previous work of our group. The segmentation for all these structures will be done with a semiautomatic proprietary algorithm developed in our group.
Measured: 1 year after the end of the intervention
Lower Body Muscle function - Baseline
Muscle function will be determined using a linear position transducer (watios and m/s). 1-RM will be also estimated from this data.
Measured: Just before the start of the 12-week intervention (-3 to -1 days)
Lower Body Muscle function - 12 weeks
Muscle function will be determined using a linear position transducer (watios and m/s). 1-RM will be also estimated from this data.
Measured: Just after the end of the 12-week intervention (+1 to +3 days)
Lower Body Muscle function - 1 year
Muscle function will be determined using a linear position transducer (watios and m/s). 1-RM will be also estimated from this data.
Measured: 1 year after the end of the intervention
Upper Body Muscle function - Baseline
Muscle function will be determined using a linear position transducer (watios and m/s). 1-RM will be also estimated from this data.
Measured: Just before the start of the 12-week intervention (-3 to -1 days)
Upper Body Muscle function - 12 weeks
Muscle function will be determined using a linear position transducer (watios and m/s). 1-RM will be also estimated from this data.
Measured: Just after the end of the 12-week intervention (+1 to +3 days)
Upper Body Muscle function - 1 year
Muscle function will be determined using a linear position transducer (watios and m/s). 1-RM will be also estimated from this data.
Measured: 1 year after the end of the intervention
Handgrip Strength - Baseline
Handgrip strength will be determined by the handgrip strength test using a digital hand dynamometer (kilograms)
Measured: Just before the start of the 12-week intervention (-3 to -1 days)
Handgrip Strength - 12 weeks
Handgrip strength will be determined by the handgrip strength test using a digital hand dynamometer (kilograms)
Measured: Just after the end of the 12-week intervention (+1 to +3 days)
Handgrip Strength - 1 year
Handgrip strength will be determined by the handgrip strength test using a digital hand dynamometer (kilograms)
Measured: 1 year after the end of the intervention
Secondary outcomes (19)
Resting energy expenditure
We will measure gas exchange to objectively determine REE and substrate oxidation rates using indirect calorimetry (Q-NRG, COSMED, Rome, Italy), the gold standard methodology, following standard procedures.
Measured: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Ectopic fat
Visceral adipose tissue and liver fat will be also measured by MRI (Magnetom Vida 3T system, Siemens, Healthineers), the gold standard methodology as previously described.
Measured: Just before the start of the 12-week intervention (-3 to -1 days), just after the end of the 12-week intervention (+1 to +3 days) and 1 year after the end of the intervention
Bone Mineral Density
Bone mineral density (g/cm2) will be measured by DXA (gold standard).
Measured: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Lean Mass
Lean mass (kg) will be measured by DXA (gold standard).
Measured: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Bone Mineral Content
Bone mineral content (g) will be measured by DXA (gold standard).
Measured: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Whole body fat percentage
Whole body fat percentage (%) will be measured by air displacement plethysmography (BodPod, COSMED, Rome, Italy) (gold standard).
Measured: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Glucose homeostasis
Glucose homeostasis will be evaluated with the continuous glucose monitoring over consecutive 24h/10 days.
Measured: Just before the start of the 12-week intervention (-12 to -3 days), just after the end of the 12-week intervention (+3 to +12 days) and 1 year after the end of the intervention
Whole body Insulin Resistance
Whole body IR with the standard 75-grams two-hour oral glucose tolerance test.
Measured: Just before the start of the 12-week intervention (-12 to -3 days), just after the end of the 12-week intervention (+3 to +12 days) and 1 year after the end of the intervention
Serum glucose
Fasting serum samples will be used to measure glucose (mg/dl)
Measured: Just before the start of the 12-week intervention (-12 to -3 days), just after the end of the 12-week intervention (+3 to +12 days) and 1 year after the end of the intervention
Serum Insulin
Fasting serum samples will be used to measure insulin (mg/dl)
Measured: Just before the start of the 12-week intervention (-12 to -3 days), just after the end of the 12-week intervention (+3 to +12 days) and 1 year after the end of the intervention
Serum adiponectin
Fasting serum samples will be used to measure adiponectin (μg/ml)
Measured: Just before the start of the 12-week intervention (-12 to -3 days), just after the end of the 12-week intervention (+3 to +12 days) and 1 year after the end of the intervention
HOMA-IR
HOMA-IR will be calculated using the following formula: [fasting serum insulin (μU/mL) × Fasting serum glucose (mg/dL)/405]
Measured: Just before the start of the 12-week intervention (-12 to -3 days), just after the end of the 12-week intervention (+3 to +12 days) and 1 year after the end of the intervention
Circulating total cholesterol
Circulating total cholesterol (mg/dL) will be measured in plasma after an overnight fast.
Measured: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
LDL-Cholesterol
LDL-Cholesterol (mg/dL) will be measured in plasma after an overnight fast.
Measured: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
HDL-Cholesterol
HDL-Cholesterol (mg/dL) will be measured in plasma after an overnight fast.
Measured: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Triglycerides
Triglycerides will be measured in plasma after an overnight fast.
Measured: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Apolipoprotein B
Apolipoprotein B (mg/dl) will be measured in plasma after an overnight fast.
Measured: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Apolipoprotein A
Apolipoprotein A (mg/dl) will be measured in plasma after an overnight fast.
Measured: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Micro RNA analyses
Expression of circulating miRNAs will be analyzed in plasma samples, using RNAseq methodology at baseline and at the end of the intervention (12-week). Briefly, total RNA will be isolate and RNA quantity and quality will be confirmed by gel electrophoresis and spectrophotometry. RNA integrity will also be assessed by 2100 Bioanalyzer of Agilent Technologies. Specific NGS library kit will be used to generate sequencing libraries. Then, fragments of 145-160bp will be selected. Library sequencing will be done on a MiSeq instrument (Illumina Inc.) using Miseq Reagent kit V3 (Illumina Inc.), 12 libraries per sequencing run will be multiplexed. Analysis of results will be performed using MiSeqReporter (MSR) software of Illumina. Sequence alignment will be done using BWA and variant calling using GATK algorithm. Changes on miRNA expression levels will be evaluated with specific software packages (SHiMPS aligner, DESeq2, miRDeep, sRNAPipe and miRNET v2.0).
Measured: Just before the start of the 12-week intervention (-7 to -3 days) and just after the end of the 12-week intervention (+3 to +7 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2023
- Study start1 Sep 2023
- Primary completionDec 2024 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Menopause Related ConditionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized controlled parallel-arm clinical trial
- Masking
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Idoia Labayen
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital of Navarra
- Responsible party
- Sponsor-investigator, Idoia Labayen, Universidad Pública de Navarra
- Investigators
- Idoia Labayen, PhD, Principal investigator, Universidad Pública de NavarraEstrella Petrina, PhD, Principal investigator, Hospital of Navarra
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05912309
- Sponsor's protocol ID
- PI_2023/8
- Other IDs
- EXP_75091
- Status last verified
- Apr 2024
- First submitted
- 17 May 2023
- Last updated
- 17 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Time-restricted Eating and Exercise Training on Skeletal Muscle Mass Quantity, Quality and Function in Postmenopausal Women With Overweight and Obesity
- ClinicalTrials.gov ID
- NCT05912309
- Acronym / sponsor ID
- PI_2023/8
- Keywords
- Obesity, Overweight, Sarcopenia, Menopause, Exercise, Resistance Exercise, Physical activity, intramuscular adipose tissue
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- Idoia LabayenUniversity, hospital or other
- Collaborators
- Hospital of Navarra
- Study start
- 1 Sep 2023 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 22 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this randomized controlled trial] is to investigate the effects of a 12-week time restricted eating (TRE) and exercise combined intervention, as compared to (i) TRE alone, and to (ii) Caloric Restriction (CR) plus the same exercise intervention elicited by the TRE group, on Skeletal muscle tissue (SMT) quantity, quality and function (primary outcome), Resting energy expenditure (REE) and cardiometabolic health (secondary outcomes), and miRNA biomarkers in postmenopausal women with overweight or obesity.
Detailed description
Time restricted eating (TRE) may be a potential lifestyle tool for the management of obesity in populations at risk of sarcopenia. However, weight loss may occur at the expense of lean mass, thus producing an undesirable reduction of Skeletal Muscle Tissue (SMT). To date, studies focused on body composition suffer from methodological shortcomings in adequate SMT quantity and quality measurement (e.g. using gold standard magnetic resonance imaging, MRI) and function, dietary intake protein counselling and the monitoring of dietary energy and macronutrient intake. Importantly, no TRE studies have been conducted in postmenopausal women with overweight who are at high risk of sarcopenia. Studies such as the one presented herein are needed to elucidate the effects of TRE on SMT and protein balance in the middle- and long-term lifestyle intervention. In addition, the potentially myoprotective roles of dietary protein and exercise need to be more cogently established within the framework of a TRE regime in populations at risk of sarcopenia. Further, the effects of TRE+exercise on SMT quantity, quality and function should be compared to currently accepted lifestyle therapy lifestyle therapy for obesity management in adults at high risk of sarcopenia (Caloric Restriction (CR) + exercise and adequate protein intake). Finally, the underlying mechanisms of SMT quantity, quality and function loss, as well as those explaining the effects of TRE and exercise are unknown. The investigators will explore circulating miRNA profiles as novel, non-invasive and feasible prognostic biomarkers of changes in SMT quantity, quality and function.
- This study will be the first randomized controlled trial to investigate whether the addition of exercise to TRE is able to reverse the SMT loss induced by the TRE alone, and if the combination of TRE and exercise confers any additional benefits on SMT quantity, quality and function above the currently recommended lifestyle intervention.
- The few previous TRE studies examined changes in body composition using dual-energy X-ray absorptiometry (DXA); however, this is not the most appropriate method to assess SMT and it does not evaluate IMAT. The investigators will use magnetic resonance imaging (MRI) scanning (gold standard) to measure changes in SMT and intra-muscular adipose tissue (IMAT, muscle quality).
- There is a lack of knowledge on the effects of TRE on muscle strength. This important determinant of sarcopenia will be assessed with gold standard methodology.
- This study will be pioneer at quantifying the long-term adherence and the persistence of the effects of TRE and exercise on SMT quantity, IMAT and function (12 months)
- Importantly, the investigators will be able to study miRNA predictors of changes in SMT quantity, IMAT and function in postmenopausal women.
- Available studies on TRE, although enlightening, have solely assessed acute or short-term (<2 weeks) effects of TRE on Resting Energy Expenditure (REE). It will be evaluated whether TRE and exercise confers any additional advantage on REE maintenance above the currently recommended lifestyle intervention in the middle and long-term.
- The majority of TRE studies were focused on body weight or total adiposity. The present study will also evaluate the effects of the intervention on specific ectopic fat depots strongly associated with cardiometabolic health, morbidity and mortality using MRI (i.e., visceral adipose tissue (VAT) and liver fat), in the middle- (12 weeks) and long-term (12 months).
- Impaired systemic glucose homeostasis is common in postmenopausal women with overweight. TRE and exercise intervention has the potential of reducing Insulin Resistance (IR); therefore, the present project will include the measurement of continuous glucose monitoring (CGM) analyzing day-to-day glucose homeostasis.
- Exercise reduces the risk of sarcopenic obesity and ectopic fat aggregation, improves cardiometabolic health and reduces proinflammatory markers, but the underlying mechanisms are largely unknown. The analysis of circulating miRNA profiles can help to elucidate the mechanisms explaining the response to the lifestyle intervention as well as identifying potential therapeutic targets.
- There is a high inter-individual variability in the response to TRE and exercise interventions, but its predictors are unknown. This study will focus on miRNAs as potential predictive and prognostic biomarkers.
- Gender dimension: women are under-represented in TRE studies and there is no previous study conducted on postmenopausal women. Studies on this specific population are of great interest for several reasons: unique hormonal status that confers elevated risk of obesity and obesity-related morbidities, high risk of sarcopenia, and an enormous interest on self-administered TRE that could entail unknown health consequences.
Participants: Postmenopausal women (n=78) with an absence of menses for over two years (at least stage +1a) and with overweight (BMI>25 kg/m2) or obesity (BMI>30 kg/m2 and BMI<=40 kg/m2) will be recruited at the Endocrinology Unit of the University Hospital of Navarra.
Intervention: Participants will be randomly allocated 1:1:1 to (1) CR+exercise, (2) TRE, and (3) TRE+exercise groups. Before baseline measurements and group allocation, there will be a 2-week lead-in period where the eating window, glucose and physical activity will be continuously monitored. Thereafter, participants will follow the 12-week intervention according to their allocated group.
- CR+exercise group: Individualized intensive behavioral intervention weight loss program including CR, exercise training and lifestyle education designed according to the current guidelines. CR will be tailored to participants (objectively assessed). Diet will provide 600 kcal/day less than the individual energy requirements based on measured REE (indirect calorimetry) and multiplied by an activity factor obtained by accelerometry. Experienced nutritionists will design personalized and balanced CR diet, and will train the participants through the food exchange system to follow the treatment. In those cases in which the CR compromised a protein intake of at least 1.2 g/kg/day, the macronutrient percentage distribution will be modified prioritizing achieving this minimum protein intake. Sport sciences specialist will design, supervise and monitor the concurrent exercise intervention following the 2020 WHO recommendations. The program will be tailored to the participant ́s ability and health, and will be focused on a gradual increase to levels that are safe. Resistance training: 2-3 times/week designed to manage, attenuate and even prevent the loss of SMT and function.
- TRE group: Participants will be required to reduce their eating time window to ≤ 8 hours/day. Women can choose when to begin eating, but the last meal should be completed before or at 20:00 hours (concentrating the eating window towards the active phase confers higher cardiometabolic health benefits). Our preliminary results suggest that this eating window is feasible and safe.
- TRE+exercise group: This group will combine the intervention of the TRE group and the same exercise intervention of the CR+exercise group. The exercise sessions will be scheduled within or immediately after their eating window in order to maximize MPS. Morning and afternoon training schedules will be offered to participants.
The three groups will receive dietary advice regarding the daily amount of high quality protein and meal-specific protein quantities. All the participants will attend a lifestyle education program based on Mediterranean diet and WHO physical activity recommendations every two weeks.
Long-term follow-up: Weight cycling is frequent in women and is associated with increased morbidity. There are no previous studies examining the persistence of the effects of TRE+exercise in the long-term. Also, it seems that the adherence to the TRE regime is higher than to the CR, but the evidence is scarce. This project will assess the main study outcomes and the adherence in order to examine the persistence and feasibility of the intervention effects 12 months after the cessation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, investigator)
- Number of arms
- 3
- Model description
- Randomized controlled parallel-arm clinical trial
| Arm | Type | Receives |
|---|---|---|
| Time Restricted Eating (TRE) | Experimental | Behavioral: Time Restricted Eating (TRE) |
| Time Restricted Eating (TRE) + Exercise | Experimental | Behavioral: Time Restricted Eating (TRE), Behavioral: Exercise |
| Caloric restriction (CR) + Exercise | Active comparator | Behavioral: Exercise, Behavioral: Caloric Restriction |
Who may qualify
- Ages
- 50 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age between 50 and 65 years.
- Menopause (Phase +1a)
- Body mass index ≥25.0 and <40 kg/m2 or waist circumference > 94 cm.
- Weight stability (within 3% of screening weight) for >3 months prior to baseline.
- Sedentary lifestyle (<150 min/week of moderate-vigorous intensity exercise) for >3 months prior to baseline.
Key exclusion criteria (10 listed)
- History of major adverse cardiovascular events, clinically significant renal, endocrine or neurological disease, bariatric surgery, HIV/AIDS, known inflammatory and/or rheumatologic disease, cancer or other medical condition in which fasting or exercise is contraindicated.
- Use of exogenous (sex) hormones (hormone replacement therapy).
- Type 1 or type 2 diabetes.
- Severe psychiatric disorders, eating disorders, sleep disorders or alcohol abuse.
- Regular use of medications or compounds that may affect study results.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Time Restricted Eating (TRE)Participants will be required to reduce their eating time window to ≤ 8 hours/day. Women can choose when to begin eating, but the last meal should be completed before or at 20:00 hours (concentrating the eating window towards the active phase confers higher cardiometabolic health benefits). Our preliminary results suggest that this eating window is feasible and safe. Participants will receive dietary advice regarding the daily amount of high quality protein and meal-specific protein quantities. All the participants will attend a lifestyle education program based on Mediterranean diet and WHO physical activity recommendations every two weeks. | Behavioural | Time Restricted Eating (TRE), Time Restricted Eating (TRE) + Exercise |
| ExerciseSport sciences specialists will design, supervise and monitor the concurrent exercise intervention following the 2020 WHO recommendations. The program will be tailored to the participant's ability and health, and will be focused on a gradual increase to levels that are safe. Resistance training: 3 times/week designed to manage, attenuate and even prevent the loss of skeletal muscle tissue and function. The exercise sessions will be scheduled within or immediately after their eating window in order to maximize muscular muscle protein synthesis. Morning and afternoon training schedules will be offered to participants. | Behavioural | Caloric restriction (CR) + Exercise, Time Restricted Eating (TRE) + Exercise |
| Caloric RestrictionIndividualised intensive behavioural intervention weight loss program including CR, exercise training and lifestyle education designed according to the current guidelines. CR will be tailored to participants (objectively assessed). Diet will provide 600 kcal/day less than the individual energy requirements based on measured resting energy expenditure (indirect calorimetry) and multiplied by an activity factor obtained by accelerometry. Experienced nutritionists will design personalized and balanced CR diet, and will train the participants through the food exchange system to follow the treatment. In those cases in which the CR compromised a protein intake of at least 1.2 g/kg/day, the macronutrient percentage distribution will be modified prioritizing achieving this minimum protein intake. | Behavioural | Caloric restriction (CR) + Exercise |
Primary outcome
Skeletal muscle tissue quantity - Baseline
Time frame: Just after the end of the 12-week intervention (+1 to +3 days)
Skeletal muscle tissue (Cross sectional area (cm2) and Volume (cm3)) will be quantified by magnetic resonance imaging ((MRI) Magnetom Vida 3T system, Siemens, Healthineers), the gold standard methodology, at the most representative sites: mid-thigh, psoas (L3) and paraspinal and abdominal wall (L2-L4). Both Detailed information about imaging segmentation and processing can be found in previous work of our group. The segmentation for all these structures will be done with a semiautomatic proprietary algorithm developed in our group.
Skeletal muscle tissue quantity - 12 weeks
Time frame: Just before the start of the 12-week intervention (-3 to -1 days), just after the end of the 12-week intervention (+1 to +3 days) and 1 year after the end of the intervention
Skeletal muscle tissue (Cross sectional area (cm2) and Volume (cm3)) will be quantified by magnetic resonance imaging ((MRI) Magnetom Vida 3T system, Siemens, Healthineers), the gold standard methodology, at the most representative sites: mid-thigh, psoas (L3) and paraspinal and abdominal wall (L2-L4). Both Detailed information about imaging segmentation and processing can be found in previous work of our group. The segmentation for all these structures will be done with a semiautomatic proprietary algorithm developed in our group.
Skeletal muscle tissue quantity - 1 year
Time frame: 1 year after the end of the intervention
Skeletal muscle tissue (Cross sectional area (cm2) and Volume (cm3)) will be quantified by magnetic resonance imaging ((MRI) Magnetom Vida 3T system, Siemens, Healthineers), the gold standard methodology, at the most representative sites: mid-thigh, psoas (L3) and paraspinal and abdominal wall (L2-L4). Both Detailed information about imaging segmentation and processing can be found in previous work of our group. The segmentation for all these structures will be done with a semiautomatic proprietary algorithm developed in our group.
Skeletal muscle tissue quality - Baseline
Time frame: Just before the start of the 12-week intervention (-3 to -1 days)
Intermuscular and Intramuscular adipose tissue (fat fraction(%)) will be quantified by magnetic resonance imaging ((MRI) Magnetom Vida 3T system, Siemens, Healthineers), the gold standard methodology, at the most representative sites: mid-thigh, psoas (L3) and paraspinal and abdominal wall (L2-L4). Both Detailed information about imaging segmentation and processing can be found in previous work of our group. The segmentation for all these structures will be done with a semiautomatic proprietary algorithm developed in our group.
Skeletal muscle tissue quality - 12 weeks
Time frame: Just after the end of the 12-week intervention (+1 to +3 days)
Intermuscular and Intramuscular adipose tissue (fat fraction(%)) will be quantified by magnetic resonance imaging ((MRI) Magnetom Vida 3T system, Siemens, Healthineers), the gold standard methodology, at the most representative sites: mid-thigh, psoas (L3) and paraspinal and abdominal wall (L2-L4). Both Detailed information about imaging segmentation and processing can be found in previous work of our group. The segmentation for all these structures will be done with a semiautomatic proprietary algorithm developed in our group.
Skeletal muscle tissue quality - 1 Year
Time frame: 1 year after the end of the intervention
Intermuscular and Intramuscular adipose tissue (fat fraction(%)) will be quantified by magnetic resonance imaging ((MRI) Magnetom Vida 3T system, Siemens, Healthineers), the gold standard methodology, at the most representative sites: mid-thigh, psoas (L3) and paraspinal and abdominal wall (L2-L4). Both Detailed information about imaging segmentation and processing can be found in previous work of our group. The segmentation for all these structures will be done with a semiautomatic proprietary algorithm developed in our group.
Lower Body Muscle function - Baseline
Time frame: Just before the start of the 12-week intervention (-3 to -1 days)
Muscle function will be determined using a linear position transducer (watios and m/s). 1-RM will be also estimated from this data.
Lower Body Muscle function - 12 weeks
Time frame: Just after the end of the 12-week intervention (+1 to +3 days)
Muscle function will be determined using a linear position transducer (watios and m/s). 1-RM will be also estimated from this data.
Lower Body Muscle function - 1 year
Time frame: 1 year after the end of the intervention
Muscle function will be determined using a linear position transducer (watios and m/s). 1-RM will be also estimated from this data.
Upper Body Muscle function - Baseline
Time frame: Just before the start of the 12-week intervention (-3 to -1 days)
Muscle function will be determined using a linear position transducer (watios and m/s). 1-RM will be also estimated from this data.
Upper Body Muscle function - 12 weeks
Time frame: Just after the end of the 12-week intervention (+1 to +3 days)
Muscle function will be determined using a linear position transducer (watios and m/s). 1-RM will be also estimated from this data.
Upper Body Muscle function - 1 year
Time frame: 1 year after the end of the intervention
Muscle function will be determined using a linear position transducer (watios and m/s). 1-RM will be also estimated from this data.
Handgrip Strength - Baseline
Time frame: Just before the start of the 12-week intervention (-3 to -1 days)
Handgrip strength will be determined by the handgrip strength test using a digital hand dynamometer (kilograms)
Handgrip Strength - 12 weeks
Time frame: Just after the end of the 12-week intervention (+1 to +3 days)
Handgrip strength will be determined by the handgrip strength test using a digital hand dynamometer (kilograms)
Handgrip Strength - 1 year
Time frame: 1 year after the end of the intervention
Handgrip strength will be determined by the handgrip strength test using a digital hand dynamometer (kilograms)
19 secondary outcomes
Resting energy expenditure
Time frame: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Ectopic fat
Time frame: Just before the start of the 12-week intervention (-3 to -1 days), just after the end of the 12-week intervention (+1 to +3 days) and 1 year after the end of the intervention
Bone Mineral Density
Time frame: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Lean Mass
Time frame: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Bone Mineral Content
Time frame: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Whole body fat percentage
Time frame: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Glucose homeostasis
Time frame: Just before the start of the 12-week intervention (-12 to -3 days), just after the end of the 12-week intervention (+3 to +12 days) and 1 year after the end of the intervention
Whole body Insulin Resistance
Time frame: Just before the start of the 12-week intervention (-12 to -3 days), just after the end of the 12-week intervention (+3 to +12 days) and 1 year after the end of the intervention
Serum glucose
Time frame: Just before the start of the 12-week intervention (-12 to -3 days), just after the end of the 12-week intervention (+3 to +12 days) and 1 year after the end of the intervention
Serum Insulin
Time frame: Just before the start of the 12-week intervention (-12 to -3 days), just after the end of the 12-week intervention (+3 to +12 days) and 1 year after the end of the intervention
Serum adiponectin
Time frame: Just before the start of the 12-week intervention (-12 to -3 days), just after the end of the 12-week intervention (+3 to +12 days) and 1 year after the end of the intervention
HOMA-IR
Time frame: Just before the start of the 12-week intervention (-12 to -3 days), just after the end of the 12-week intervention (+3 to +12 days) and 1 year after the end of the intervention
Circulating total cholesterol
Time frame: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
LDL-Cholesterol
Time frame: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
HDL-Cholesterol
Time frame: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Triglycerides
Time frame: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Apolipoprotein B
Time frame: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Apolipoprotein A
Time frame: Just before the start of the 12-week intervention (-7 to -3 days), just after the end of the 12-week intervention (+3 to +7 days) and 1 year after the end of the intervention
Micro RNA analyses
Time frame: Just before the start of the 12-week intervention (-7 to -3 days) and just after the end of the 12-week intervention (+3 to +7 days)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Idoia Labayen, PhD principal investigator
Universidad Pública de Navarra
Estrella Petrina, PhD principal investigator
Hospital of Navarra
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Time Restricted Eating (TRE), Exercise and Caloric Restriction in people with Menopause Related Conditions and Sarcopenia, run by Idoia Labayen at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Idoia Labayen, PhD (644699839 ext. +34, idoia.labayen@unavarra.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Skeletal muscle tissue quantity - Baseline (time frame: Just after the end of the 12-week intervention (+1 to +3 days)). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2024.