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

Physical Activity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02552355
• Other study ID #: 15-8573H
• Status: Completed
• Phase: Phase 2
• Start date: August 2015
• Est. completion date: August 2017

Study information

• Verified date: April 2019
• Source: Colorado State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a randomized, placebo controlled, double blind study. 60 men and women over the age of 55 with indications of pre-diabetes will be recruited for participation and randomly assigned to one of four 12 week exercise training programs: 1)Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of Metformin. 2) Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of Metformin. 3) Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of matching placebo. 4) Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of placebo.

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. The titration dosing scheme and taking metformin/placebo with meals will help reduce the most common side effects (i.e.,gastrointestinal discomfort). If participants experience gastrointestinal discomfort, the dose will be lowered to 1500 mg/day.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

• 55 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Glucose Intolerance
• Physical Activity
• Prediabetic State

Intervention

Drug:
• Metformin
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.
• Placebo
Daily administration of matching placebo during a 12 week exercise training program.

Dietary Supplement:
• Carbohydrate Beverage
Supervised aerobic exercise 3 days per week followed by a carbohydrate drink
• Protein Beverage
Supervised aerobic exercise 3 days per week followed by a protein drink

Locations

Country	Name	City	State
United States	Colorado State University, Dept. of Health and Exercise Science	Fort Collins	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Colorado State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	DNA Synthesis	Incorporation of Deuterium Oxide into DNA will be measured before and after the 12 week interventions.	Baseline and 12 weeks
Primary	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	Intracellular Signaling Proteins	Protein content of intracellular signaling proteins that are implicated in mitochondrial biogenesis, mitochondrial function and insulin sensitivity were measured by Western blotting. Densitometry results are reported as a ratio of protein divided by total amount of protein expressed. All proteins of interest are expressed as phosphorylated relative to total. These data are reported as the percent change from baseline compared to 12 weeks.	Baseline and 12 weeks
Secondary	Glucose Profiles From Real-Time Continuous Glucose Monitoring	Data derived from Continuous Glucose Monitoring was used to calculate mean glucose and mean average glucose excursions (MAGE). These data are reported as the percent change at baseline (pre), 6-8 weeks (Mid), and 12 weeks (post) .	Baseline, Weeks 6-8, 12 weeks

External Links

•   Final Publication
•   Lab website