Calorie Restriction, Protein Supplementation and Metabolic Health

Obesity Clinical Trial

— CRPS  

Official title:

Calorie Restriction and Metabolic Health

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01538836
• Other study ID #: CRPS-201107354
• Secondary ID: 1R01DK094483-01A
• Status: Completed
• Phase: N/A
• First received: February 20, 2012
• Last updated: March 22, 2017
• Start date: January 2012
• Est. completion date: March 2017

Study information

• Verified date: March 2017
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: March 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 50 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Menopause
• Obesity
• Osteoporosis
• Sarcopenia

Intervention

Behavioral:
• Weight loss with normal protein intake
Goal of 8 to 10% weight loss while consuming the recommended daily allowance of protein (i.e, 0.8 grams of protein per kg body weight per day).
• Weight loss with protein supplementation
Goal of 8 to 10% weight loss while consuming 150% of the recommended daily allowance of protein (i.e., 1.2 grams of protein per kg body weight per day).

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. Erratum in: Gastroenterology. 2009 Jul;137(1):393. Mayurranjan, Mitra S [corrected to Mayurranjan S Mitra]. — View 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. — View 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: 10.111 — View 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 — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in muscle volume	Thigh muscle volume will be measured by magnetic resonance imaging (MRI)	Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Primary	Change in muscle strength	Muscle strength will be evaluated by administering maximum one repetition strength and isokinetic strength tests.	Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Primary	Changes in bone mineral density and bone mineral content	Total bone mass and total body and regional bone mineral density will be evaluated by using dual X-ray energy absorptiometry (DXA).	Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Secondary	Change in insulin sensitivity	Insulin sensitivity (glucose rate of disappearance [Rd] during a hyperinsulinemic-euglycemic clamp procedure) will be evaluated in a subset of 10 participants per group because power analysis has determined that this number is sufficient to detect a 25% difference between groups assuming 80% power, an alpha value of 0.05 and an average baseline insulin-stimulated glucose Rd of 2,590 ± 492 µmol/min, the average ± SD insulin stimulated glucose Rd the investigators have measured during the past 20 y in obese subjects. In the investigators' experience (Kirk et al., 2009 and Magkos et al., 2016), the weight loss induced increase in insulin stimulated glucose Rd is ~50%.	Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Secondary	Change in muscle protein metabolism	Rates of muscle protein synthesis, breakdown and net protein balance will be assessed during postabsorptive conditions and when insulin and/or amino acid concentrations are elevated.	Baseline and at 5% weight loss in the calorie restriction groups and after ~3 months in the weight maintenance group
Secondary	Change in bacterial populations found in the stool		Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Secondary	Change in cell proliferation (growth) rates in the colon	Colon cell proliferation rates will be determined using stable isotope labelled tracer methods in conjunction with sigmoid colon biopsy samples	Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Secondary	Determine the acute effect of whey protein ingestion on skeletal muscle insulin sensitivity	Insulin sensitivity will be evaluated using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope labeled tracer infusions	Prior to starting the weight loss or maintenance intervention
Secondary	Determine the acute effect of whey protein ingestion on muscle protein metabolism	Rates of muscle protein synthesis, breakdown and net protein balance will be assessed using stable isotope labeled tracer methods during postabsorptive conditions and during insulin infusion with or without whey protein ingestion	Prior to starting the weight loss or maintenance intervention