Milk Protein Feeding After Aerobic Exercise in Older Adults With Pre-diabetes Taking the Biguanide Metformin

NCT02552355 | Completed Phase 2 Results

• 1 other identifier: 15-8573H
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose that post-exercise milk protein feeding will enhance the mitochondrial protein synthesis (biogenesis) response to an exercise-training program. In addition, the investigators propose that this stimulatory effect of protein feeding will overcome the potential blunting effect of metformin on exercise responses. The investigators will investigate these outcomes over a 12-week exercise-training program in older adults with pre-diabetes with or without metformin treatment.

Conditions

Physical Activity

Outcome Measures

Primary Outcomes (7)

• Mitochondrial Function

  Oxygen consumption was assessed via high-resolution mitochondrial respirometry in permeabilized skeletal muscle. This outcome was assessed via 2 different protocols; Protocol 1 was a substrate-uncoupler-inhibitor titration (SUIT) and Protocol 2 was an adenosine diphosphate (ADP) titration. These data are reported as the percent change from baseline compared to 12 weeks.

  Baseline and 12 weeks

• Protein Synthesis

  Incorporation of deuterium into proteins to calculate cumulative synthesis rates. Protein synthesis was measured in sub cellular fractions of skeletal muscle including mixed, cytoplasmic and mitochondrial enriched fractions. These data are reported as the mean at 12 weeks.

  12 weeks

• Body Composition

  Dual energy x-ray absorptiometry was used to assess fat-free and fat mass. These data are reported as the mean at baseline (pre) and mean at 12 weeks (post).

  Baseline and 12 weeks

• Insulin Sensitivity

  Oral glucose tolerance test was used to measure whole-body insulin sensitivity. These data are reported as the mean at baseline (pre) and the mean at 12 weeks (post).

  Baseline and 12 weeks

• Peak Aerobic Capacity

  Indirect calorimetry was used to measure peak oxygen consumption during a maximal, graded exercise test. These data are reported as the percent change from baseline compared to 12 weeks.

  Baseline and 12 weeks

• DNA Synthesis

  Incorporation of Deuterium Oxide into DNA will be measured before and after the 12 week interventions.

  Baseline and 12 weeks

• Glucose Tolerance

  Oral glucose tolerance test was used to measure glucose tolerance. These data are reported as the mean at baseline (pre) and the mean at 12 weeks (post).

  Baseline and 12 weeks

Secondary Outcomes (2)

• Intracellular Signaling Proteins

  Baseline and 12 weeks

• Glucose Profiles From Real-Time Continuous Glucose Monitoring

  Baseline, Weeks 6-8, 12 weeks

Study Arms (4)

Metformin/Carbohydrate

EXPERIMENTAL

Daily oral administration of Metformin with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week 4. Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of Metformin.

Drug: Metformin; Dietary Supplement: Carbohydrate Beverage

Placebo/Carbohydrate

PLACEBO COMPARATOR

Daily oral administration of matching placebo with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of matching placebo will begin as one tablet for the first week and will increase by one tablet/day/week until reaching 4 tablets by week 4. Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of matching placebo.

Drug: Placebo; Dietary Supplement: Carbohydrate Beverage

Metformin/Protein

ACTIVE COMPARATOR

Daily oral administration of Metformin with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week. Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of Metformin

Drug: Metformin; Dietary Supplement: Protein Beverage

Placebo/Protein

ACTIVE COMPARATOR

Daily oral administration of Metformin with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week. Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of placebo.

Drug: Placebo; Dietary Supplement: Protein Beverage

Interventions

Metformin DRUG

Daily administration of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week 4 during a 12 week exercise training program.

Also known as: Glumetza, Fortamet, Glucophage, Riomet

Metformin/Carbohydrate; Metformin/Protein

Placebo DRUG

Daily administration of matching placebo during a 12 week exercise training program.

Placebo/Carbohydrate; Placebo/Protein

Carbohydrate Beverage DIETARY_SUPPLEMENT

Supervised aerobic exercise 3 days per week followed by a carbohydrate drink

Metformin/Carbohydrate; Placebo/Carbohydrate

Protein Beverage DIETARY_SUPPLEMENT

Supervised aerobic exercise 3 days per week followed by a protein drink

Metformin/Protein; Placebo/Protein

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• Individuals with Prediabetes defined as impaired fasting glucose (100 to 126 mg/dl), HbA1c (5.7-6.4%), and/or impaired glucose tolerance defined as 2 hour postprandial blood glucose of 140 to 200 mg/dl.

You may not qualify if:

• Medications contraindicated with Metformin (Dofetilide, Lamotrigine, Pegvisomant, Somatropin, Trimethoprim, Trospium, Gatifloxacin, Cephalexin, Cimetidine, Dalfampridine)
• Recent (less than 6 weeks) or planned imaging that requires IV contrast,
• Renal dysfunction creatinine ≥ 1.3 mg/dL in men or ≥ 1.2 mg/dL in women
• Alanine Aminotransferase (ALT) levels exceed 52 IU/L
• Heart, Kidney or Liver Disease
• Type I or Type II Diabetes
• Anti-coagulant therapy (warfarin/heparin)
• Lung/respiratory dysfunction
• Medications affecting primary outcomes
• Lactose Intolerant
• Tobacco Use
• Heavy Alcohol Use
• Cancer
• Lidocaine Allergy

Sponsors & Collaborators

• Colorado State University: lead

Study Sites (1)

Colorado State University, Dept. of Health and Exercise Science

Fort Collins, Colorado, 80523-1582, United States

Location

Related Links

• Lab website
• Final Publication

MeSH Terms

Conditions

Motor Activity

Interventions

Metformin

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Manager of Research Operations
• Organization: Colorado State University

Laurie.Biela@colostate.edu

9704912242

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Participants were assigned to either Metformin-Protein, Metformin-Carbohydrate, Placebo-Protein, and Placebo-Carbohydrate.

Study Record Dates

• First Submitted: September 1, 2015
• First Posted: September 17, 2015
• Study Start: August 1, 2015
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: April 30, 2019
• Results First Posted: April 10, 2019

Record last verified: 2019-04

Locations

US (1)