Ignite Creation Date:
2024-05-06 @ 3:47 PM
Last Modification Date:
2024-10-26 @ 1:56 PM
Study NCT ID:
NCT04751916
Status:
RECRUITING
Last Update Posted:
2023-04-04
First Post:
2021-02-02
Brief Title:
Nutritional Stimulation of Muscle Protein Synthesis and Metabolic Rate After Bariatric Surgery
Sponsor:
Oregon Health and Science University
Organization:
Oregon Health and Science University
Study Overview
Official Title:
Nutritional Stimulation of Muscle Protein Synthesis and Metabolic Rate After Bariatric Surgery
Status:
RECRUITING
Status Verified Date:
2023-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Bariatric surgery is an effective treatment for severe obesity but results in loss of muscle mass The investigators will test the hypothesis that consumption of an Essential Amino Acid-based nutritional formulation will maintain muscle mass while stimulating fat loss after bariatric surgery
Detailed Description:
1 Objectives
Bariatric surgery has become a common treatment for severe obesity and results in a loss of fat mass However muscle mass is also lost following bariatric surgery It is the investigators overarching premise that consumption of the Essential Amino Acid-based nutritional formulation following bariatric surgery will preserve muscle mass by stimulating muscle protein synthesis As a result the energy utilization associated with the combination of maintained muscle mass and stimulated muscle protein synthesis will counter the decrease in metabolic rate that normally occurs in hypocaloric circumstances Maintenance of a higher total energy expenditure by Essential Amino Acid consumption will accelerate loss of body fat as well as accelerate loss of body weight The investigators further propose that consumption of an Essential Amino Acid-based nutritional formulation will reduce muscle intra-cellular lipid accumulation which will translate to greater improvements in glucose homeostasis and muscle protein metabolism The loss of muscle mass in those with obesity undergoing rapid weight loss post-bariatric surgery is not in itself a disease or a medical condition
The following aims will test specific hypotheses related to the scientific premise
Aim 1 Supplementation of the usual diet following bariatric surgery with a proprietary Essential Amino Acid-based nutritional formulation twice per day for 6 months will maintain muscle mass and reduce fat mass more than supplementation of the diet with an isonitrogenous amount of whey protein Muscle mass will be directly measured using a novel tracer-dilution technique using deuterium-labeled creatine Fat mass and lean body mass will be measured by Dual-energy X-ray absorptiometry
Aim 2 Muscle protein fractional synthetic rate and total muscle protein synthesis muscle mass x fractional synthetic rate will decline less from pre-surgery values in participants consuming the Essential Amino Acid-based nutritional formulation as compared to whey protein Muscle protein fractional synthetic rate will be measured by the novel virtual biopsy method which provides an integrated value over three weeks
Aim 3 The pre-surgery rate of total energy expenditure will be better maintained in participants consuming the Essential Amino Acid-based nutritional formulation as opposed to whey protein Change in total energy expenditure will be measured over 10-day intervals using the doubly-labeled water technique before to 6 months following surgery
Aim 4 Six months after bariatric surgery muscle intra-cellular lipid accumulation will be reduced from the pre-surgery value to a greater extent in participants consuming the Essential Amino Acid-based nutritional formulation than whey protein Muscle intra-cellular lipid accumulation will be measured by means of magnetic resonance spectroscopy and magnetic resonance imaging The investigators anticipate that a greater reduction in intra-cellular lipid accumulation will be related to greater improvement in insulin sensitivity in terms of glucose homeostasis and also in terms of muscle protein synthesis
Positive results of this study will support the value of the Essential Amino Acid-based nutritional formulation in terms of increasing the rate of fat loss and improving body composition changes following bariatric surgery
2 Background
Despite successful weight loss and improvement of comorbidities after bariatric surgery most patients with severe obesity remain overweight Patients also experience variation in treatment response Up to 30 patients experience sub-optimal weight loss or significant weight regain Amount of weight lost and its maintenance are important because they are what lead to improvementremission of comorbidities diabetes heart disease etc and to decreased mortality from cardiovascular disease or cancer One of the keys to optimal weight loss from a calorie restricted diet and subsequent weight-loss maintenance is losing fat without losing muscle aka lean body mass It is decreased energy expenditure from decreased muscle mass after weight loss which contributes significantly to weight regain Muscle mass is the key driver of energy metabolism favoring the burning of food as fuel rather than its storage as fat Since muscle provides a reservoir of amino acids to maintain protein synthesis essential for survival its mass quantity is always at risk under conditions of inadequate dietary intake Skeletal muscle under the caloric restriction of weight-loss diets catabolizes to provide the bodys unmet protein needs It becomes challenging to maintain muscle in conditions of severe calorie restriction such as after bariatric surgery
Protein supplementation has been shown to protect against muscle loss experienced in weight loss but only if supplementation is sufficient The standard of care approach to maintain muscle mass during rapid significant weight loss after bariatric surgery has been dietary whey protein supplementation After bariatric surgery protein supplementation is limited by the inability of patients to take in sufficient calories This can be further hindered by typical perioperative complications which limit intake such as nausea vomiting and early satiety Therefore despite standard of care supplementation with whey protein post bariatric surgery only marginal gains in preventing muscle loss have been made Essential Amino Acid the intervention supplement in this study is a patented formula scientifically shown to be far more anabolic than whey protein in free-living elderly and young healthy adults undergoing bedrest The Essential Amino Acid supplement stimulates protein synthesis 3-5 times as effectively as whey protein with negligible non-protein calories
The importance of the role of muscle in weight loss and its maintenance cannot be overemphasized Muscle crucial to energy metabolism is responsible for the majority of total energy expenditure equivalent to physical activity energy expenditure resting energy expenditure and diet induced thermogenesis - calories required to digest food Both physical activity and muscle protein synthesis comprise a significant portion of energy expenditure Through its function in physical activity and protein synthesis muscle largely determines the caloric expenditure underlying the ability to use up food eaten rather than store it as fat
Obesity is not just increased body fat but also increased intramuscular fat The intramuscular fat associated with obesity impairs the muscle function of providing normal glucose homeostasis Fortunately when fat stored in muscle decreases insulin sensitivity improves Also impaired under conditions of increased intramuscular fat is the function of providing amino acids to maintain essential protein synthesis Impaired muscle mitochondria-stimulated protein synthesis potentially decreases resting energy expenditure and diet induced thermogenesis Adequate protein supplementation can counter muscle mitochondrial protein synthesis impairment and in theory lead to decreased intramuscular fat improving both energy expenditure and insulin sensitivity
3 Study Design
This is a double-blinded randomized clinical trial in which the responses to consumption of one of two different dietary supplements following bariatric surgery will be determined A variety of factors related to body composition and muscle metabolism will be quantified in participants with obesity before and approximately 6 months after bariatric surgery This interval of time was selected because additional body weight changes are generally relatively small 6 months after surgery most of the weight loss occurs in the first 6 months Participants will be assigned randomly by computer to receive either an Essential Amino Acid based nutritional supplement intervention or a commercially-available whey protein supplement Beneprotein
Bariatric surgery has become a common treatment for severe obesity and results in a loss of fat mass However muscle mass is also lost following bariatric surgery It is the investigators overarching premise that consumption of the Essential Amino Acid-based nutritional formulation following bariatric surgery will preserve muscle mass by stimulating muscle protein synthesis As a result the energy utilization associated with the combination of maintained muscle mass and stimulated muscle protein synthesis will counter the decrease in metabolic rate that normally occurs in hypocaloric circumstances Maintenance of a higher total energy expenditure by Essential Amino Acid consumption will accelerate loss of body fat as well as accelerate loss of body weight The investigators further propose that consumption of an Essential Amino Acid-based nutritional formulation will reduce muscle intra-cellular lipid accumulation which will translate to greater improvements in glucose homeostasis and muscle protein metabolism The loss of muscle mass in those with obesity undergoing rapid weight loss post-bariatric surgery is not in itself a disease or a medical condition
The following aims will test specific hypotheses related to the scientific premise
Aim 1 Supplementation of the usual diet following bariatric surgery with a proprietary Essential Amino Acid-based nutritional formulation twice per day for 6 months will maintain muscle mass and reduce fat mass more than supplementation of the diet with an isonitrogenous amount of whey protein Muscle mass will be directly measured using a novel tracer-dilution technique using deuterium-labeled creatine Fat mass and lean body mass will be measured by Dual-energy X-ray absorptiometry
Aim 2 Muscle protein fractional synthetic rate and total muscle protein synthesis muscle mass x fractional synthetic rate will decline less from pre-surgery values in participants consuming the Essential Amino Acid-based nutritional formulation as compared to whey protein Muscle protein fractional synthetic rate will be measured by the novel virtual biopsy method which provides an integrated value over three weeks
Aim 3 The pre-surgery rate of total energy expenditure will be better maintained in participants consuming the Essential Amino Acid-based nutritional formulation as opposed to whey protein Change in total energy expenditure will be measured over 10-day intervals using the doubly-labeled water technique before to 6 months following surgery
Aim 4 Six months after bariatric surgery muscle intra-cellular lipid accumulation will be reduced from the pre-surgery value to a greater extent in participants consuming the Essential Amino Acid-based nutritional formulation than whey protein Muscle intra-cellular lipid accumulation will be measured by means of magnetic resonance spectroscopy and magnetic resonance imaging The investigators anticipate that a greater reduction in intra-cellular lipid accumulation will be related to greater improvement in insulin sensitivity in terms of glucose homeostasis and also in terms of muscle protein synthesis
Positive results of this study will support the value of the Essential Amino Acid-based nutritional formulation in terms of increasing the rate of fat loss and improving body composition changes following bariatric surgery
2 Background
Despite successful weight loss and improvement of comorbidities after bariatric surgery most patients with severe obesity remain overweight Patients also experience variation in treatment response Up to 30 patients experience sub-optimal weight loss or significant weight regain Amount of weight lost and its maintenance are important because they are what lead to improvementremission of comorbidities diabetes heart disease etc and to decreased mortality from cardiovascular disease or cancer One of the keys to optimal weight loss from a calorie restricted diet and subsequent weight-loss maintenance is losing fat without losing muscle aka lean body mass It is decreased energy expenditure from decreased muscle mass after weight loss which contributes significantly to weight regain Muscle mass is the key driver of energy metabolism favoring the burning of food as fuel rather than its storage as fat Since muscle provides a reservoir of amino acids to maintain protein synthesis essential for survival its mass quantity is always at risk under conditions of inadequate dietary intake Skeletal muscle under the caloric restriction of weight-loss diets catabolizes to provide the bodys unmet protein needs It becomes challenging to maintain muscle in conditions of severe calorie restriction such as after bariatric surgery
Protein supplementation has been shown to protect against muscle loss experienced in weight loss but only if supplementation is sufficient The standard of care approach to maintain muscle mass during rapid significant weight loss after bariatric surgery has been dietary whey protein supplementation After bariatric surgery protein supplementation is limited by the inability of patients to take in sufficient calories This can be further hindered by typical perioperative complications which limit intake such as nausea vomiting and early satiety Therefore despite standard of care supplementation with whey protein post bariatric surgery only marginal gains in preventing muscle loss have been made Essential Amino Acid the intervention supplement in this study is a patented formula scientifically shown to be far more anabolic than whey protein in free-living elderly and young healthy adults undergoing bedrest The Essential Amino Acid supplement stimulates protein synthesis 3-5 times as effectively as whey protein with negligible non-protein calories
The importance of the role of muscle in weight loss and its maintenance cannot be overemphasized Muscle crucial to energy metabolism is responsible for the majority of total energy expenditure equivalent to physical activity energy expenditure resting energy expenditure and diet induced thermogenesis - calories required to digest food Both physical activity and muscle protein synthesis comprise a significant portion of energy expenditure Through its function in physical activity and protein synthesis muscle largely determines the caloric expenditure underlying the ability to use up food eaten rather than store it as fat
Obesity is not just increased body fat but also increased intramuscular fat The intramuscular fat associated with obesity impairs the muscle function of providing normal glucose homeostasis Fortunately when fat stored in muscle decreases insulin sensitivity improves Also impaired under conditions of increased intramuscular fat is the function of providing amino acids to maintain essential protein synthesis Impaired muscle mitochondria-stimulated protein synthesis potentially decreases resting energy expenditure and diet induced thermogenesis Adequate protein supplementation can counter muscle mitochondrial protein synthesis impairment and in theory lead to decreased intramuscular fat improving both energy expenditure and insulin sensitivity
3 Study Design
This is a double-blinded randomized clinical trial in which the responses to consumption of one of two different dietary supplements following bariatric surgery will be determined A variety of factors related to body composition and muscle metabolism will be quantified in participants with obesity before and approximately 6 months after bariatric surgery This interval of time was selected because additional body weight changes are generally relatively small 6 months after surgery most of the weight loss occurs in the first 6 months Participants will be assigned randomly by computer to receive either an Essential Amino Acid based nutritional supplement intervention or a commercially-available whey protein supplement Beneprotein
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 1R44DK125151 | NIH | None | httpsreporternihgovquickSearch1R44DK125151 |