Clinical trial NCT04282603: Nutritional Strategies for Metabolic Health in Aging
Official title: Nutritional Strategies for Metabolic Health in Aging
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Sarcopenic Obesity
Keywords: Adipose tissue
Skeletal Muscle
Physical Function
Lead sponsor: University of Alaska Fairbanks
Sponsor class: OTHER
First posted: 2020-02-25
Enrollment: 6
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study design is a randomized, double blind, two arm study, where one arm receives a standard meal replacement (Bariatrics Advantage), and the other an enhanced one (ie., EMR) for 24 weeks, including a caloric restriction period of 12 weeks, and a maintenance period of 12 weeks.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Lean tissue mass and adipose tissue mass
timeFrame: 24 weeks for each participant
measure: Skeletal muscle
timeFrame: 24 weeks for each participant
measure: Metabolic health
timeFrame: 24 weeks for each participant
measure: Intrahepatic lipid
timeFrame: 24 weeks for each participant
measure: Physical function
timeFrame: 24 weeks for each participant
measure: Gut microbiome
timeFrame: 24 weeks for each participant
Secondary outcomes:
measure: Timed step test
timeFrame: 24 weeks for each participant
measure: Timed floor transfer test
timeFrame: 24 weeks for each participant
measure: Hand grip test
timeFrame: 24 weeks for each participant
Other outcomes:
Locations:
city: Fairbanks
country: United States
facility: University of Alaska Fairbanks
state: Alaska
Study officials:
affiliation: University of Alaska Fairbanks
name: Robert H Coker, PhD
role: PRINCIPAL_INVESTIGATOR
References: