Clinical trial NCT01538836: Calorie Restriction, Protein Supplementation and Metabolic Health
Official title: Calorie Restriction and Metabolic Health
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Menopause
Osteoporosis
Sarcopenia
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2012-02-24
Enrollment: 75
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether consuming additional protein during calorie restriction induced weight loss has beneficial or harmful effects on multi-organ (liver, muscle, adipose tissue) insulin sensitivity, colonocyte proliferation rates, the gut microbiome, muscle mass and function, and bone mineral density in obese, postmenopausal women.


Eligibility criteria: Inclusion Criteria:

* Obese with body mass index (BMI) between 30 and 50 kg/m2
* Postmenopausal
* Sedentary (i.e., less than 1.5 hours of exercise per week)

Exclusion Criteria:

* Individuals with diabetes and/or uncontrolled hypertension
* Individuals with hepatitis B and/or C
* Individuals who smoke
* Individuals with an allergy to whey protein

Primary outcomes:
measure: Change in muscle volume
timeFrame: Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
measure: Change in muscle strength
timeFrame: Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
measure: Changes in bone mineral density and bone mineral content
timeFrame: Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Secondary outcomes:
measure: Change in insulin sensitivity
timeFrame: Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
measure: Change in muscle protein metabolism
timeFrame: Baseline and at 5% weight loss in the calorie restriction groups and after ~3 months in the weight maintenance group
measure: Change in bacterial populations found in the stool
timeFrame: Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
measure: Change in cell proliferation (growth) rates in the colon
timeFrame: Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
measure: Determine the acute effect of whey protein ingestion on skeletal muscle insulin sensitivity
timeFrame: Prior to starting the weight loss or maintenance intervention
measure: Determine the acute effect of whey protein ingestion on muscle protein metabolism
timeFrame: Prior to starting the weight loss or maintenance intervention
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Bettina Mittendorfer, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kirk E, Reeds DN, Finck BN, Mayurranjan SM, Patterson BW, Klein S. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology. 2009 May;136(5):1552-60. doi: 10.1053/j.gastro.2009.01.048. Epub 2009 Jan 25.
citation: Magkos F, Bradley D, Eagon JC, Patterson BW, Klein S. Effect of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding on gastrointestinal metabolism of ingested glucose. Am J Clin Nutr. 2016 Jan;103(1):61-5. doi: 10.3945/ajcn.115.116111. Epub 2015 Nov 25.
citation: Smith GI, Yoshino J, Kelly SC, Reeds DN, Okunade A, Patterson BW, Klein S, Mittendorfer B. High-Protein Intake during Weight Loss Therapy Eliminates the Weight-Loss-Induced Improvement in Insulin Action in Obese Postmenopausal Women. Cell Rep. 2016 Oct 11;17(3):849-861. doi: 10.1016/j.celrep.2016.09.047.
citation: Smith GI, Patterson BW, Klein SJ, Mittendorfer B. Effect of hyperinsulinaemia-hyperaminoacidaemia on leg muscle protein synthesis and breakdown: reassessment of the two-pool arterio-venous balance model. J Physiol. 2015 Sep 15;593(18):4245-57. doi: 10.1113/JP270774. Epub 2015 Aug 14.
citation: Smith GI, Yoshino J, Stromsdorfer KL, Klein SJ, Magkos F, Reeds DN, Klein S, Mittendorfer B. Protein Ingestion Induces Muscle Insulin Resistance Independent of Leucine-Mediated mTOR Activation. Diabetes. 2015 May;64(5):1555-63. doi: 10.2337/db14-1279. Epub 2014 Dec 4.
citation: Smith GI, Commean PK, Reeds DN, Klein S, Mittendorfer B. Effect of Protein Supplementation During Diet-Induced Weight Loss on Muscle Mass and Strength: A Randomized Controlled Study. Obesity (Silver Spring). 2018 May;26(5):854-861. doi: 10.1002/oby.22169.
citation: Harris LLS, Smith GI, Patterson BW, Ramaswamy RS, Okunade AL, Kelly SC, Porter LC, Klein S, Yoshino J, Mittendorfer B. Alterations in 3-Hydroxyisobutyrate and FGF21 Metabolism Are Associated With Protein Ingestion-Induced Insulin Resistance. Diabetes. 2017 Jul;66(7):1871-1878. doi: 10.2337/db16-1475. Epub 2017 May 4.