Impact of Protein and Alkali Supplementation on Skeletal Muscle in Older Adults

• ClinicalTrials.gov Identifier: NCT04048616
• Recruitment Status: Recruiting
• First Posted: August 7, 2019
• Last Update Posted: April 27, 2022
• Sponsor: Tufts University
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): Lisa Ceglia, Tufts University

Study Description

Brief Summary:

Whether higher dietary protein benefits skeletal muscle health in older adults remains an ongoing area of investigation. This study will determine whether adding an alkaline salt supplement, potassium bicarbonate, to reduce the dietary acid load of a high protein diet can further enhance the beneficial impact of a high protein diet alone on muscle performance and mass in older underactive adults on baseline low protein diet.

Condition or disease	Intervention/treatment	Phase
Age-Related Sarcopenia; Muscle Loss	Dietary Supplement: whey protein isolate; Dietary Supplement: potassium bicarbonate (KHCO3); Other: microcrystalline cellulose; Other: maltodextrin powder	Not Applicable

Detailed Description:

With aging, skeletal muscle mass and performance decline leading to an increased risk of falls and physical disability. There is ongoing research on whether increasing dietary protein intake in older adults improves indices of muscle health and thus translates to a reduction in physical disability. A main concern is that high protein results in a large dietary acid load from the breakdown of protein to acidogenic byproducts, which could in turn promote muscle degradation particularly in older adults with age-related declines in renal excretion of acid. The scientific premise of this project is that the balance between the amount of protein in the diet (anabolic component) and the net acid load of the diet (catabolic component) in part determines whether the diet as a whole has a net anabolic or catabolic effect on muscle. Preliminary data have suggested that a daily alkaline salt supplement (potassium bicarbonate, KHCO3) lowered the dietary acid load and improved lower extremity muscle power in postmenopausal women. The investigator's central hypothesis is that higher protein intake plus a neutralizing alkaline salt will have additive effects on muscle performance and mass in older adults to either intervention alone. To test the hypothesis, the investigators will conduct a randomized, double-blind, placebo-controlled, 2x2 factorial study in which underactive men and women age 65 and older on baseline lower protein diets will be enrolled. Participants will assigned to one of four groups: either a whey protein supplement (to raise protein intake to 1.5 g/kg/d) with or without KHCO3 81 mmol/d or an isocaloric placebo supplement with or without KHCO3 81 mmol/d for 24 wks. The primary outcome is lower extremity muscle power at 24 weeks. Secondary outcomes are lower extremity muscle power at 12 weeks, muscle endurance at 12 and 24 weeks, physical performance at 24 weeks, lean mass at 24 weeks, and 24-hr urinary nitrogen excretion adjusted for nitrogen intake at 24 weeks. Exploratory outcomes will include a measure of muscle mass - D3-creatine dilution - and how it correlates with lean mass. Changes in these outcomes will be compared in the 4 groups. If successful, this research would represent a meaningful step in defining the circumstances under which protein has its greatest anabolic benefit.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Intervention Model Description: double blind randomized placebo controlled 2x2 factorial design
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Impact of Protein and Alkali Supplementation on Skeletal Muscle in Older Adults
• Actual Study Start Date: November 1, 2019
• Estimated Primary Completion Date: May 1, 2023
• Estimated Study Completion Date: May 1, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: whey protein isolate + KHCO3; 1.5 gm/kg/day of whey protein and 81 mmol/day of KHCO3	Dietary Supplement: whey protein isolate; one 15-25 gm (based on body weight) protein packet three times a day with each meal; Dietary Supplement: potassium bicarbonate (KHCO3); two 13.5 mmol capsules three times a day with each meal
Active Comparator: whey protein isolate + microcrystalline cellulose; 1.5 gm/kg/day of whey protein and identical placebo microcrystalline cellulose capsules	Dietary Supplement: whey protein isolate; one 15-25 gm (based on body weight) protein packet three times a day with each meal; Other: microcrystalline cellulose; identical placebo capsule
Active Comparator: maltodextrin powder + KHCO3; isocaloric placebo maltodextrin powder and 81 mmol/day of KHCO3	Dietary Supplement: potassium bicarbonate (KHCO3); two 13.5 mmol capsules three times a day with each meal; Other: maltodextrin powder; isocaloric placebo powder
Placebo Comparator: maltodextrin powder + microcrystalline cellulose; isocaloric placebo maltodextrin powder and identical placebo microcrystalline cellulose capsules	Other: microcrystalline cellulose; identical placebo capsule; Other: maltodextrin powder; isocaloric placebo powder

Outcome Measures

Primary Outcome Measures :

1. lower extremity muscle power [ Time Frame: 24 weeks ]
   measure of muscle power using a double leg press

Secondary Outcome Measures :

1. lower extremity muscle power [ Time Frame: 12 weeks ]
   measure muscle power using double leg press
2. isokinetic leg extension strength and endurance [ Time Frame: 12 and 24 weeks ]
   measure knee extension strength, torque and fatigability using Biodex Isokinetic Dynamometer
3. handgrip strength [ Time Frame: 24 weeks ]
   measure strength using grip strength dynamometer
4. appendicular lean body mass [ Time Frame: 24 weeks ]
   Dual energy X-ray absorptiometry (DXA) lean mass of arms plus legs divided by height squared
5. physical performance battery [ Time Frame: 24 weeks ]
   measure performance based on Health Aging and Body Composition-Physical Performance Battery
6. 24 hour urinary nitrogen excretion to nitrogen intake [ Time Frame: 24 weeks ]
   measure based on 24 hour urine and 24 hour diet recall

Other Outcome Measures:

1. D3-creatine dilution (exploratory) [ Time Frame: 24 weeks ]
   measure of total body muscle mass

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. ability to sign informed consent form
2. ambulatory community-dwelling men and women
3. age 65 years and over
4. habitual dietary intake of protein of ≤0.8 g/kg/d
5. underactive
6. estimated glomerular filtration rate ≥ 50 ml/min/1.73 m2

Exclusion Criteria:

1. participation in a diet or intensive exercise program during the study
2. vegetarian (no animal protein)
3. oral glucocorticoid use for > 10 days in the last 3 months
4. anabolic and gonadal hormones in the last 6 months
5. Tamoxifen/raloxifene in the last 6 months
6. regular use of alkali-producing antacids (> 3 times per week)
7. potassium-containing supplements or products
8. non-steroidal anti-inflammatory medications >3 times per week
9. antacids containing calcium carbonate, aluminum hydroxide, magnesium hydroxide, or calcium acetate
10. insulin
11. sulfonylureas
12. SGLT2 inhibitors
13. a lower extremity fracture in the last year
14. kidney stones in the past 5 years
15. hyperkalemia
16. elevated serum bicarbonate
17. hypercalcemia
18. uncontrolled diabetes mellitus defined as having fasting blood >150 or hemoglobin A1c >8%
19. untreated thyroid or parathyroid disease
20. significant immune disorder
21. current unstable heart disease
22. Crohn's disease
23. active malignancy or cancer therapy in the last year
24. alcohol use exceeding 2 drinks/day
25. current peptic ulcers or esophageal stricture
26. other condition or abnormality in screening labs, at discretion of the study physician

Contacts and Locations

Contacts

Contact: Lisa Ceglia, MD MS; 617-556-3085; lisa.ceglia@tufts.edu

Contact: Elise Reitshamer; 617-556-3265; elise.reitshamer@tufts.edu

Locations

United States, Massachusetts

Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University; Recruiting

Boston, Massachusetts, United States, 02111

Contact: Lisa Ceglia 617-556-3085 ext 6175563085 lisa.ceglia@tufts.edu

Contact: Lisa Ceglia 6175563085 ext 6175563085 lisa.ceglia@tufts.edu

Sponsors and Collaborators

Tufts University

National Institute on Aging (NIA)

Investigators

• Principal Investigator: Lisa Ceglia, MD MS; Tufts Medical Center and Tufts University

More Information

• Responsible Party: Lisa Ceglia, Asst. Professor of Medicine, Tufts University
• ClinicalTrials.gov Identifier: NCT04048616
• Other Study ID Numbers: 3010; 1R01AG055443-01A1 ( U.S. NIH Grant/Contract )
• First Posted: August 7, 2019
• Last Update Posted: April 27, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Sarcopenia; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical