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Calorie Restriction, Protein Supplementation and Metabolic Health (CRPS)

Primary Purpose

Obesity, Menopause, Osteoporosis

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Weight loss with normal protein intake
Weight loss with protein supplementation
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obesity

Eligibility Criteria

50 Years - 65 Years (Adult, Older Adult)FemaleAccepts Healthy Volunteers

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

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Active Comparator

Experimental

Arm Label

Weight maintenance

Weight loss with normal protein intake

Weight loss with protein supplementation

Arm Description

Weight maintenance with normal protein intake

Outcomes

Primary Outcome Measures

Change in muscle volume
Thigh muscle volume will be measured by magnetic resonance imaging (MRI)
Change in muscle strength
Muscle strength will be evaluated by administering maximum one repetition strength and isokinetic strength tests.
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).

Secondary Outcome Measures

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%.
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.
Change in bacterial populations found in the stool
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
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
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

Full Information

First Posted
February 20, 2012
Last Updated
March 22, 2017
Sponsor
Washington University School of Medicine
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT01538836
Brief Title
Calorie Restriction, Protein Supplementation and Metabolic Health
Acronym
CRPS
Official Title
Calorie Restriction and Metabolic Health
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
January 2012 (Actual)
Primary Completion Date
March 2017 (Actual)
Study Completion Date
March 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Menopause, Osteoporosis, Sarcopenia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
75 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Weight maintenance
Arm Type
No Intervention
Arm Description
Weight maintenance with normal protein intake
Arm Title
Weight loss with normal protein intake
Arm Type
Active Comparator
Arm Title
Weight loss with protein supplementation
Arm Type
Experimental
Intervention Type
Behavioral
Intervention Name(s)
Weight loss with normal protein intake
Intervention Description
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).
Intervention Type
Behavioral
Intervention Name(s)
Weight loss with protein supplementation
Intervention Description
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).
Primary Outcome Measure Information:
Title
Change in muscle volume
Description
Thigh muscle volume will be measured by magnetic resonance imaging (MRI)
Time Frame
Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Title
Change in muscle strength
Description
Muscle strength will be evaluated by administering maximum one repetition strength and isokinetic strength tests.
Time Frame
Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Title
Changes in bone mineral density and bone mineral content
Description
Total bone mass and total body and regional bone mineral density will be evaluated by using dual X-ray energy absorptiometry (DXA).
Time Frame
Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Secondary Outcome Measure Information:
Title
Change in insulin sensitivity
Description
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%.
Time Frame
Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Title
Change in muscle protein metabolism
Description
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.
Time Frame
Baseline and at 5% weight loss in the calorie restriction groups and after ~3 months in the weight maintenance group
Title
Change in bacterial populations found in the stool
Time Frame
Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Title
Change in cell proliferation (growth) rates in the colon
Description
Colon cell proliferation rates will be determined using stable isotope labelled tracer methods in conjunction with sigmoid colon biopsy samples
Time Frame
Baseline and at 10% weight loss in calorie restriction groups and ~6 to 7 months in the weight maintenance group
Title
Determine the acute effect of whey protein ingestion on skeletal muscle insulin sensitivity
Description
Insulin sensitivity will be evaluated using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope labeled tracer infusions
Time Frame
Prior to starting the weight loss or maintenance intervention
Title
Determine the acute effect of whey protein ingestion on muscle protein metabolism
Description
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
Time Frame
Prior to starting the weight loss or maintenance intervention

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bettina Mittendorfer, PhD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19208352
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. Erratum In: Gastroenterology. 2009 Jul;137(1):393. Mayurranjan, Mitra S [corrected to Mayurranjan S Mitra].
Results Reference
background
PubMed Identifier
26607940
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.
Results Reference
background
PubMed Identifier
27732859
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.
Results Reference
result
PubMed Identifier
26150260
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.
Results Reference
result
PubMed Identifier
25475435
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.
Results Reference
result
PubMed Identifier
29687650
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.
Results Reference
derived
PubMed Identifier
28473464
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.
Results Reference
derived

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Calorie Restriction, Protein Supplementation and Metabolic Health

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