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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01AG055443-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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The central hypothesis is that higher protein intake and a neutralizing alkaline salt supplement will improve muscle performance and mass, compared to their respective placebos, in older men and postmenopausal women.
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 and a neutralizing alkaline salt will improve muscle performance and mass, compared to their respective placebos, in older men and postmenopausal women. To test the hypothesis, the investigators conducted a randomized, double-blind, placebo-controlled, 2x2 factorial study in underactive men and women age 65 and older on baseline lower protein diets. Participants were 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| whey protein isolate + KHCO3 | Active Comparator | 1.5 gm/kg/day of whey protein and 81 mmol/day of KHCO3 |
|
| whey protein isolate + microcrystalline cellulose | Active Comparator | 1.5 gm/kg/day of whey protein and identical placebo microcrystalline cellulose capsules |
|
| maltodextrin powder + KHCO3 | Active Comparator | isocaloric placebo maltodextrin powder and 81 mmol/day of KHCO3 |
|
| maltodextrin powder + microcrystalline cellulose | Placebo Comparator | isocaloric placebo maltodextrin powder and identical placebo microcrystalline cellulose capsules |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| whey protein isolate | Dietary Supplement | one 15-25 gm (based on body weight) protein packet three times a day with each meal |
|
| Measure | Description | Time Frame |
|---|---|---|
| Double Leg Press Peak Power at 70% | Double leg press peak power at 70% of the 1 repetition maximum | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Double Leg Press Peak Power at 70% | Double leg press peak power at 70% of the 1-repetition maximum | 12 weeks |
| Double Leg Press Peak Power at 40% | Double leg press peak power at 40% of the 1 repetition maximum |
| Measure | Description | Time Frame |
|---|---|---|
| D3-creatine Muscle Mass/Weight | measure of total body percent muscle mass by D3-creatine dilution method | 24 weeks |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lisa Ceglia, MD MS | Tufts Medical Center and Tufts University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University | Boston | Massachusetts | 02111 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41780731 | Derived | Ceglia L, Konieczynski E, Danico E, Trinquart L, Koethe B, Xiang Q, Fielding RA, Evans WJ, Shankaran M, Dawson-Hughes B. Independent effects of whey protein and alkali supplementation on muscle health in healthy older adults: factorial randomized controlled trial. Am J Clin Nutr. 2026 May;123(5):101257. doi: 10.1016/j.ajcnut.2026.101257. Epub 2026 Mar 2. |
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Exclusion criteria included use of oral glucocorticoids, anabolic and gonadal hormones, alkali-producing antacids, potassium-containing supplements, insulin, uncontrolled diabetes mellitus, kidney stones, advanced chronic kidney disease, cirrhosis, gastroesophageal or intestinal disease, immune disorders, unstable heart disease, untreated thyroid or parathyroid disease, active malignancy or cancer therapy, recent fracture, milk protein allergy, and relevant laboratory abnormalities.
From July 2021 to July 2023, ambulatory, community-dwelling men and postmenopausal women aged 65 years and older were recruited from direct mailings to the HNRCA volunteer database and the Tufts Medical Center patient database.
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| ID | Title | Description |
|---|---|---|
| FG000 | Whey Protein Isolate + KHCO3 | 1.5 gm/kg/day of whey protein and 81 mmol/day of KHCO3 whey protein isolate: one 15-25 gm (based on body weight) protein packet three times a day with each meal potassium bicarbonate (KHCO3): two 13.5 mmol capsules three times a day with each meal |
| FG001 | Whey Protein Isolate + Microcrystalline Cellulose | 1.5 gm/kg/day of whey protein and identical placebo microcrystalline cellulose capsules whey protein isolate: one 15-25 gm (based on body weight) protein packet three times a day with each meal microcrystalline cellulose: identical placebo capsule |
| FG002 | Maltodextrin Powder + KHCO3 | isocaloric placebo maltodextrin powder and 81 mmol/day of KHCO3 potassium bicarbonate (KHCO3): two 13.5 mmol capsules three times a day with each meal maltodextrin powder: isocaloric placebo powder |
| FG003 | Maltodextrin Powder + Microcrystalline Cellulose | isocaloric placebo maltodextrin powder and identical placebo microcrystalline cellulose capsules microcrystalline cellulose: identical placebo capsule maltodextrin powder: isocaloric placebo powder |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Intention-to-Treat sample of 128 participants with available outcome data.
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| ID | Title | Description |
|---|---|---|
| BG000 | Whey Protein Isolate + KHCO3 | 1.5 gm/kg/day of whey protein and 81 mmol/day of KHCO3 whey protein isolate: one 15-25 gm (based on body weight) protein packet three times a day with each meal potassium bicarbonate (KHCO3): two 13.5 mmol capsules three times a day with each meal |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Double Leg Press Peak Power at 70% | Double leg press peak power at 70% of the 1 repetition maximum | Analysis used an at-the-margins approach to evaluate the superiority of whey protein (WP) against placebo-WP and of potassium bicarbonate (KHCO3) against placebo-KHCO3 | Posted | Mean | 95% Confidence Interval | Watts | 24 weeks |
|
up to 24 weeks
Standard definitions
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Whey Protein Isolate + KHCO3 | 1.5 gm/kg/day of whey protein and 81 mmol/day of KHCO3 whey protein isolate: one 15-25 gm (based on body weight) protein packet three times a day with each meal potassium bicarbonate (KHCO3): two 13.5 mmol capsules three times a day with each meal |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pedal edema | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lisa Ceglia, MD MS | Tufts University and Tufts Medical Center | (617) 636-8171 | lisa.ceglia@tuftsmedicine.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 4, 2022 | Apr 1, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 23, 2024 | Apr 1, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009133 | Muscular Atrophy |
| ID | Term |
|---|---|
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D001284 | Atrophy |
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| ID | Term |
|---|---|
| C026329 | potassium bicarbonate |
| C109691 | microcrystalline cellulose |
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double blind randomized placebo controlled 2x2 factorial design
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| potassium bicarbonate (KHCO3) | Dietary Supplement | two 13.5 mmol capsules three times a day with each meal |
|
| microcrystalline cellulose | Other | identical placebo capsule |
|
| maltodextrin powder | Other | isocaloric placebo powder |
|
| 24 weeks |
| Double Leg Press Peak Power at 40% | Double leg press peak power at 40% of the 1 repetition maximum | 12 weeks |
| Knee Extension Peak Torque | Knee extension peak torque at 60 degrees/s using Biodex Isokinetic Dynamometer | 24 weeks |
| Knee Extension Peak Torque | Knee extension peak torque at 60 degrees/s using Biodex Isokinetic Dynamometer | 12 weeks |
| Handgrip Strength | Measure maximum handgrip strength in either hand using handheld Jamar+ dynamometer | 24 weeks |
| Appendicular Lean Body Mass/Height Squared | Dual energy X-ray absorptiometry (DXA) lean mass of arms plus legs divided by height squared | 24 weeks |
| Physical Performance Battery Score | Performance score (range 0-4 with higher values representing a better performance) based on Health Aging and Body Composition-Physical Performance Battery | 24 weeks |
| 24 Hour Urinary Total Nitrogen Excretion | Measure based on 24 hour urine total nitrogen excretion | 24 weeks |
| Whey Protein Isolate + Microcrystalline Cellulose |
1.5 gm/kg/day of whey protein and identical placebo microcrystalline cellulose capsules whey protein isolate: one 15-25 gm (based on body weight) protein packet three times a day with each meal microcrystalline cellulose: identical placebo capsule |
| BG002 | Maltodextrin Powder + KHCO3 | isocaloric placebo maltodextrin powder and 81 mmol/day of KHCO3 potassium bicarbonate (KHCO3): two 13.5 mmol capsules three times a day with each meal maltodextrin powder: isocaloric placebo powder |
| BG003 | Maltodextrin Powder + Microcrystalline Cellulose | isocaloric placebo maltodextrin powder and identical placebo microcrystalline cellulose capsules microcrystalline cellulose: identical placebo capsule maltodextrin powder: isocaloric placebo powder |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | Potassium Bicarbonate (KHCO3) | Combined participants assigned to the KHCO3 + WP group and the KHCO3 + maltodextrin placebo |
| OG003 | Placebo-KHCO3 | Combined participants assigned to the microcrystalline cellulose placebo + WP group and the microcrystalline cellulose placebo + maltodextrin placebo group |
|
|
| Secondary | Double Leg Press Peak Power at 70% | Double leg press peak power at 70% of the 1-repetition maximum | Analysis used an at-the-margins approach to evaluate the superiority of whey protein (WP) against placebo-WP and of potassium bicarbonate (KHCO3) against placebo-KHCO3 | Posted | Mean | 95% Confidence Interval | Watts | 12 weeks |
|
|
|
| Secondary | Double Leg Press Peak Power at 40% | Double leg press peak power at 40% of the 1 repetition maximum | Analysis used an at-the-margins approach to evaluate the superiority of whey protein (WP) against placebo-WP and of potassium bicarbonate (KHCO3) against placebo-KHCO3 | Posted | Mean | 95% Confidence Interval | Watts | 24 weeks |
|
|
|
| Secondary | Double Leg Press Peak Power at 40% | Double leg press peak power at 40% of the 1 repetition maximum | Analysis used an at-the-margins approach to evaluate the superiority of whey protein (WP) against placebo-WP and of potassium bicarbonate (KHCO3) against placebo-KHCO3 | Posted | Mean | 95% Confidence Interval | Watts | 12 weeks |
|
|
|
| Secondary | Knee Extension Peak Torque | Knee extension peak torque at 60 degrees/s using Biodex Isokinetic Dynamometer | Analysis used an at-the-margins approach to evaluate the superiority of whey protein (WP) against placebo-WP and of potassium bicarbonate (KHCO3) against placebo-KHCO3 | Posted | Mean | 95% Confidence Interval | Newton-meters | 24 weeks |
|
|
|
| Secondary | Knee Extension Peak Torque | Knee extension peak torque at 60 degrees/s using Biodex Isokinetic Dynamometer | Posted | Mean | 95% Confidence Interval | Newton-meters | 12 weeks |
|
|
|
| Secondary | Handgrip Strength | Measure maximum handgrip strength in either hand using handheld Jamar+ dynamometer | Analysis used an at-the-margins approach to evaluate the superiority of whey protein (WP) against placebo-WP and of potassium bicarbonate (KHCO3) against placebo-KHCO3 | Posted | Mean | 95% Confidence Interval | kg | 24 weeks |
|
|
|
| Secondary | Appendicular Lean Body Mass/Height Squared | Dual energy X-ray absorptiometry (DXA) lean mass of arms plus legs divided by height squared | Analysis used an at-the-margins approach to evaluate the superiority of whey protein (WP) against placebo-WP and of potassium bicarbonate (KHCO3) against placebo-KHCO3 | Posted | Mean | 95% Confidence Interval | kg/m^2 | 24 weeks |
|
|
|
| Secondary | Physical Performance Battery Score | Performance score (range 0-4 with higher values representing a better performance) based on Health Aging and Body Composition-Physical Performance Battery | Analysis used an at-the-margins approach to evaluate the superiority of whey protein (WP) against placebo-WP and of potassium bicarbonate (KHCO3) against placebo-KHCO3 | Posted | Mean | 95% Confidence Interval | score on a scale | 24 weeks |
|
|
|
| Secondary | 24 Hour Urinary Total Nitrogen Excretion | Measure based on 24 hour urine total nitrogen excretion | Analysis used an at-the-margins approach to evaluate the superiority of whey protein (WP) against placebo-WP and of potassium bicarbonate (KHCO3) against placebo-KHCO3 | Posted | Mean | 95% Confidence Interval | g | 24 weeks |
|
|
|
| Other Pre-specified | D3-creatine Muscle Mass/Weight | measure of total body percent muscle mass by D3-creatine dilution method | Analysis used an at-the-margins approach to evaluate the superiority of whey protein (WP) against placebo-WP and of potassium bicarbonate (KHCO3) against placebo-KHCO3 | Posted | Mean | 95% Confidence Interval | percentage of muscle mass | 24 weeks |
|
|
|
| Post-Hoc | IGF-1 | Serum insulin-like growth factor 1 (IGF-1) level | Posted | Mean | 95% Confidence Interval | ng/mL | 24 weeks |
|
|
|
| 0 |
| 35 |
| 3 |
| 35 |
| 22 |
| 35 |
| EG001 | Whey Protein Isolate + Microcrystalline Cellulose | 1.5 gm/kg/day of whey protein and identical placebo microcrystalline cellulose capsules whey protein isolate: one 15-25 gm (based on body weight) protein packet three times a day with each meal microcrystalline cellulose: identical placebo capsule | 0 | 36 | 2 | 36 | 14 | 36 |
| EG002 | Maltodextrin Powder + KHCO3 | isocaloric placebo maltodextrin powder and 81 mmol/day of KHCO3 potassium bicarbonate (KHCO3): two 13.5 mmol capsules three times a day with each meal maltodextrin powder: isocaloric placebo powder | 0 | 35 | 3 | 35 | 18 | 35 |
| EG003 | Maltodextrin Powder + Microcrystalline Cellulose | isocaloric placebo maltodextrin powder and identical placebo microcrystalline cellulose capsules microcrystalline cellulose: identical placebo capsule maltodextrin powder: isocaloric placebo powder | 1 | 35 | 3 | 35 | 14 | 35 |
| Cardiovascular event | Vascular disorders | Systematic Assessment |
|
| Fall with musculoskeletal complication | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Peptic ulcer | Gastrointestinal disorders | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Systematic Assessment |
|
| Myocardial infaction | Cardiac disorders | Systematic Assessment |
|
| coronary heart disease | Cardiac disorders | Systematic Assessment |
|
| Ear infection | Ear and labyrinth disorders | Systematic Assessment |
|
| Benign Positional Vertgo | Ear and labyrinth disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | Systematic Assessment |
|
| Respiratory infections | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| GERD | Gastrointestinal disorders | Systematic Assessment |
|
| Peptic ulcer | Gastrointestinal disorders | Systematic Assessment |
|
| Fall with injury | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Joint pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Leg cramps | General disorders | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Systematic Assessment |
|
| Basal cell cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Depression | Psychiatric disorders | Systematic Assessment |
|
| Prostate problems | Renal and urinary disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| cerebrovascular event | Vascular disorders | Systematic Assessment |
|
| Dental infection | General disorders | Systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | Systematic Assessment |
|
| Hyperkalemia | General disorders | Systematic Assessment |
|
| Lightheadedness | General disorders | Systematic Assessment |
|
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| D020763 |
| Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |