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Nutritional Strategies for Metabolic Health in Aging

Phase 1
Terminated
Conditions
Sarcopenic Obesity
Interventions
Combination Product: Weight Loss and Weight Maintenance
Registration Number
NCT04282603
Lead Sponsor
University of Alaska Fairbanks
Brief Summary

Sarcopenic obesity in older individuals presents a clinical conundrum without an effective therapeutic strategy. This study will determine the impact of precision amino acid delivery as part of a meal replacement (EMR) during weight loss on the preservation of lean tissue and improvements in metabolic health and physical function in older obese adults. Following weight loss, the investigators will examine whether one serving/day of EMR will sustain the above stated benefits.

Detailed Description

The health status of the aging population is negatively affected by sarcopenic obesity as described by the progressive loss of lean tissue and an increase in adipose tissue. This condition presents a clinical conundrum as it predisposes older obese individuals to a high risk for disability, morbidity and mortality. Insulin resistance, chronic inflammation, elevations in intrahepatic lipid and detrimental alterations in the gut microbiome are also evident. The application of caloric restriction-induced weight loss (CRWL) used to address these health risks in younger individuals may exacerbate muscle wasting and increase morbidity in older adults. Unfortunately, low fitness levels and poor compliance limit the mitigating influence of weight loss through exercise training on sarcopenic obesity. In order to address anabolic resistance or the decreased ability to maintain protein synthesis that contributes to sarcopenic obesity, the investigators have developed a complete meal replacement that contains a mechanism-targeted profile of essential amino acids (17 grams). This profile is designed to overcome anabolic resistance and maintain net protein balance even in the hypocaloric state. It is our overarching hypothesis that EMR will promote the retention of lean tissue mass, and improve metabolic and functional outcomes following 12 weeks of CRWL, and that those endpoints will be sustained over a 12 week maintenance period with the once per day (q.d.) consumption of EMR. The investigators will randomly assign older obese individuals to either EMR or an isocaloric serving of Bariatrics Advantage (meal replacement that contains 27 grams of intact protein) during these interventions. The investigators will execute these specific aims to test our hypotheses: SA1. Establish the importance of EMR in the preservation of lean tissue mass during CRWL. Lean tissue mass and adipose tissue mass will be determined by dual energy x-ray absorptiometry (DXA) and magnetic resonance imaging/spectroscopy (MRI/MRS) scans. MRI/MRS will be used to measure intrahepatic lipid, and the investigators will evaluate alterations in insulin sensitivity using the HOMA score. The investigators will measure potential changes in gut microbiota in collaboration with Dr. Duddleston at the University of Alaska Anchorage. SA2. Determine the influence of EMR on physical function and increased daily activity during CRWL. Slow walking speed is a strong predictor of morbidity and mortality. The investigators chose the 6-minute walk test to represent the primary endpoint for this aim. The investigators will also determine alterations in gait speed, skeletal muscle power and strength and stair climbing ability, and changes in physical activity using Actigraph GT3X+ devices. SA3. Identify whether EMR q.d. will sustain improvements in body composition, physical function and metabolic parameters over a 12 week, maintenance period following CRWL. Since the preservation of lean tissue mass is directly linked to optimal function and metabolic health, the investigators will measure the influence of EMR q.d. on the indices of metabolic health (ie., intrahepatic lipid, insulin sensitivity) and physical function.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
6
Inclusion Criteria
  • 60-80 years of age
  • Body mass index of 30-40 kg/m2
  • Participants must be capable of understanding the consent process
  • Participants must be capable of signing the consent form
  • Participants must have access to transportation to the clinic site
Exclusion Criteria
  • Creatinine >1.6
  • Serum glutamate pyruvate transaminase >2 times normal
  • Resting blood pressure above 160/90 mmHg
  • Use of Gemfibrozil
  • Use of corticosteroids
  • Previously diagnosed diabetes (fasting blood glucose ≥ 126 mg/dl)
  • History of kidney or liver disease
  • Heart disease as indicated by interventional procedures
  • Recent history of alcoholism
  • Physical or neurological disorder that would prevent them from completing the functional tests
  • Lactose intolerance
  • Active cancer within the last two years
  • Chronic inflammatory conditions that preclude completion of functional tests

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Bariatrics Advantage Meal ReplacementWeight Loss and Weight MaintenanceParticipants randomized to this arm will consume 5 servings/day of Bariatrics Advantage meal replacement in conjunction of 400 kcal of solid food for 12 weeks during the weight loss portion of the trial. This will be followed by the consumption of 1 serving/day of Bariatrics Advantage meal replacement for 12 weeks during the weight maintenance portion of the trial.
Experimental Meal ReplacementWeight Loss and Weight MaintenanceParticipants randomized to this arm will consume 5 servings/day of experimental meal replacement in conjunction of 400 kcal of solid food for 12 weeks during the weight loss portion of the trial. This will be followed by the consumption of 1 serving/day of experimental meal replacement for 12 weeks during the weight maintenance portion of the trial.
Primary Outcome Measures
NameTimeMethod
Metabolic health24 weeks for each participant

The investigators will evaluate alterations in insulin sensitivity using the HOMA score.

Intrahepatic lipid24 weeks for each participant

Magnetic resonance imaging and spectroscopy scans will be used to measure intrahepatic lipid

Gut microbiome24 weeks for each participant

Stool kits will be provided with standardized instructions to participants for collection and transportation of stool samples. DNA will be extracted to evaluate alterations in gut microbiota.

Skeletal muscle24 weeks for each participant

Magnetic resonance imaging scans will be used to measure the cross sectional area of skeletal muscle

Physical function24 weeks for each participant

A 6-minute walk test will be used to assess changes in physical function.

Lean tissue mass and adipose tissue mass24 weeks for each participant

Lean tissue mass and adipose tissue mass will be determined by dual energy x-ray absorptiometry.

Secondary Outcome Measures
NameTimeMethod
Timed step test24 weeks for each participant

This test will be used to evaluate dynamic balance ability. The participant will step and down from a 4 inch bench as quickly as possible 5 times.

Timed floor transfer test24 weeks for each participant

This test will be used to evaluate mobility. While being timed, the participant will start in the standing position, go to the supine position and return to the standing position.

Hand grip test24 weeks for each participant

This test will determine muscle strength. The participant will grip the hand dynamometer and perform three tests, alternating with a brief rest period of 20 seconds.

Trial Locations

Locations (1)

University of Alaska Fairbanks

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Fairbanks, Alaska, United States

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