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Musculoskeletal Effects of Bicarbonate

Primary Purpose

Muscle Loss, Fractures, Osteoporosis, Age Related

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
potassium bicarbonate
potassium bicarbonate
Inactive placebo capsule
Sponsored by
Tufts University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Muscle Loss focused on measuring potassium bicarbonate, urinary N-telopeptide, urinary nitrogen, net acid excretion

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • men and women
  • age 60 and older
  • community dwelling
  • women 1 yr since last menses

Exclusion Criteria:

Medications:

  1. Oral glucocorticoids for > 10 days in the last 3 months

    • Cortef (hydrocortisone)
    • Prednisone

  2. Parenteral glucocorticoids

    • Decadron (dexamethasone)

  3. Osteoporosis medications in the last 6 months

    • Forteo (teriparatide)
    • Calcimar, Miacalcin (calcitonin)
    • Evista (raloxifene)

  4. Osteoporosis medications in the last 2 years

    • Fosamax (alendronate)
    • Didronel (etidronate)
    • Aredia (pamidronate)
    • Actonel (risedronate)
    • Reclast (zoledronate)
  5. Tamoxifen in the last 6 months

  6. Calcium/Parathyroid

    • Rocaltrol (calcitriol)
    • Zemplar (paricalcitol)
    • Drisdol, Ergocalciferol

  7. Diuretics currently

    • hydrocholorothiazide (HCTZ)
    • Diuril (chlorothiazide)
    • Thalitone (chlorthalidone)
    • Zaroxolyn (metolazone)
    • Dyazide
    • Maxide
    • Moduretic
    • Lasix (forosamine)
    • Dyrenium (triamterene)
    • Midamor
  8. Testosterone or estrogen in the last 6 months (vaginal estrogen okay)

  9. Angiotensin converting enzyme (ACE) inhibitors currently

    • Benazepril (Lotensin)
    • Captopril (Capoten)
    • Enalapril (Vasotec)
    • Fosinopril (Monopril)
    • Lisinopril (Prinivil, Zestril)
    • Moexipril (Univasc)
    • Perindopril (Aceon)
    • Quinapril (Accupril)
    • Ramipril (Altace)
    • Trandolapril (Mavik)

  10. Angiotensin II receptor blockers currently

    • Candesartan (Atacand)
    • Eprosartan (Teveten)
    • Irbesartan (Avapro)
    • Losartan (Cozaar)
    • Olmesartan (Benicar)
    • Telmisartan (Micardis)
    • Valsartan (Diovan)

Over-the-Counter Drugs currently

  1. Antacids - any antacid that contains calcium carbonate, aluminum hydroxide, magnesium hydroxide, or calcium acetate - selected examples include

    • TUMS
    • Mylanta
    • Maalox
    • Titralac
    • Rolaids
    • Sodium bicarbonate (baking soda)
    • Note: magaldrate or Riopan® is allowed
  2. Potassium supplements
  3. Salt substitutes

Conditions/Diseases

  1. renal disease including kidney stones in the past 5 years or glomerular filtration rate (GFR) < 60 ml/min/1.73 m2
  2. hyperkalemia (serum potassium >5.3 meq/L; normal range 3.5-5.3 meq/L)
  3. elevated serum bicarbonate (serum bicarbonate > 29 mmol/L; normal range 22-29 mmol/L)
  4. cirrhosis
  5. gastroesophageal reflux disease (GERD) requiring treatment with alkali-containing antacids (TUMS, Mylanta, Maalox, Titralac, Rolaids, or sodium bicarbonate)
  6. hyperparathyroidism
  7. untreated thyroid disease
  8. significant immune disorder such as rheumatoid arthritis
  9. current unstable heart disease
  10. active malignancy or cancer therapy in the last year
  11. fasting spot urine calcium/creatinine > 0.38 mmol/mmol after 1 wk off of calcium supplements
  12. congestive heart failure, arrhythmias (surgically treated arrhythmias acceptable), or myocardial infarction in last 12 months
  13. serum calcium outside the normal range of 8.3-10.2 mg/dl
  14. uncontrolled diabetes mellitus (fasting blood sugar > 130)
  15. alcohol use exceeding 2 drinks/day
  16. peptic ulcers or esophageal stricture
  17. weight <45 or >113.5 kg (<99 or >249.7 lbs)
  18. other abnormalities in screening labs, at discretion of the study physician (the PI)

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

potassium bicarbonate low dose

potassium bicarbonate higher dose

placebo

Arm Description

potassium bicarbonate in dose of 1.0 mmol/kg per day, given in three even daily doses after meals with a full glass of water

potassium bicarbonate in dose of 1.5 mmol/kg per day, given in three even daily doses after meals with a full glass of water

microcrystalline cellulose

Outcomes

Primary Outcome Measures

The Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptide
Describe and compare changes in urinary N-telopeptide (NTX) across the placebo and Potassium Bicarbonate (KHCO3) doses.
Co-primary Aim - to Identify the Dose of KHCO3 Needed for Maximal Suppression of 24-hr Urinary Nitrogen
Describe and compare changes in 24-hour urinary nitrogen in the low and high dose and KHCO3 group and in placebo.

Secondary Outcome Measures

Full Information

First Posted
November 16, 2011
Last Updated
September 18, 2015
Sponsor
Tufts University
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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1. Study Identification

Unique Protocol Identification Number
NCT01475214
Brief Title
Musculoskeletal Effects of Bicarbonate
Official Title
Musculoskeletal Benefits of Bicarbonate in Older Adults - A Dose-Finding Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tufts University
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
With aging, men and women develop a mild and progressive metabolic acidosis. This occurs as a result of declining renal function and ingestion of acid-producing diets. There is extensive evidence that severe metabolic acidosis causes bone and muscle loss, but the impact of the chronic, mild acidosis on bone and muscle in older individuals has not been established. In a recent study, administration of a single dose of bicarbonate daily for 3 months significantly reduced urinary excretion of N-telopeptide (NTX), a marker of bone resorption and urinary nitrogen, a marker of muscle wasting and improved muscle performance in the women but not the men. These and other data support a potential role for bicarbonate as a means of reducing the musculoskeletal declines that lead to extensive morbidity and mortality in the elderly. Before proceeding to a long-term bicarbonate intervention study, however, it is important to identify the dose of bicarbonate most likely to be optimal and to characterize the subjects who benefit most from it. This double blind, placebo controlled, dose-finding study will evaluate the effects of placebo and two doses of bicarbonate on urinary NTX and nitrogen excretion and on lower extremity performance over a 3 month period in 138 men and 138 women, age 60 and older. Changes in urinary excretion of NTX and nitrogen and in selected measures of lower extremity performance will be compared across the three groups. The safety and tolerability of the interventions will also be evaluated. This investigation should provide needed information on the appropriate dosing regimen for men and women and on the study population that should be enrolled in a future bicarbonate intervention trial to assess the long-term effects of this simple, low cost intervention on important clinical outcomes including rates of loss in bone and muscle mass, falls, and fractures.
Detailed Description
This dose-finding study will evaluate the effects of placebo and two doses of bicarbonate on urinary NTX and nitrogen excretion and on lower extremity performance over a three month period. The lower dose is similar to the dose shown in our recent trial to be effective. This study is a double blind, randomized, placebo-controlled, parallel-group trial in which 138 healthy men and 138 women, age 60 and older, will take potassium bicarbonate in doses of 1.0 or 1.5 mmol/kg of body weight or placebo daily for three months. Changes in urinary excretion of NTX and nitrogen and in measures of lower extremity performance will be compared across the three groups. The safety and tolerability of the interventions will also be evaluated. This investigation should provide needed information on the appropriate dosing regimen and on the study population that should be enrolled in a future bicarbonate intervention trial to assess the long-term effects of this simple, low cost intervention on important clinical outcomes including rates of loss in bone and muscle mass, falls, and fractures.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscle Loss, Fractures, Osteoporosis, Age Related, Fall Injury
Keywords
potassium bicarbonate, urinary N-telopeptide, urinary nitrogen, net acid excretion

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
244 (Actual)

8. Arms, Groups, and Interventions

Arm Title
potassium bicarbonate low dose
Arm Type
Active Comparator
Arm Description
potassium bicarbonate in dose of 1.0 mmol/kg per day, given in three even daily doses after meals with a full glass of water
Arm Title
potassium bicarbonate higher dose
Arm Type
Active Comparator
Arm Description
potassium bicarbonate in dose of 1.5 mmol/kg per day, given in three even daily doses after meals with a full glass of water
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
microcrystalline cellulose
Intervention Type
Dietary Supplement
Intervention Name(s)
potassium bicarbonate
Intervention Description
potassium bicarbonate in dose of 1.0 mmol/kg per day, given in three even daily doses after meals with a full glass of water
Intervention Type
Dietary Supplement
Intervention Name(s)
potassium bicarbonate
Intervention Description
potassium bicarbonate in dose of 1.5 mmol/kg per day, given in three even daily doses after meals with a full glass of water
Intervention Type
Other
Intervention Name(s)
Inactive placebo capsule
Intervention Description
microcrystalline cellulose
Primary Outcome Measure Information:
Title
The Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptide
Description
Describe and compare changes in urinary N-telopeptide (NTX) across the placebo and Potassium Bicarbonate (KHCO3) doses.
Time Frame
84 days
Title
Co-primary Aim - to Identify the Dose of KHCO3 Needed for Maximal Suppression of 24-hr Urinary Nitrogen
Description
Describe and compare changes in 24-hour urinary nitrogen in the low and high dose and KHCO3 group and in placebo.
Time Frame
84 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: men and women age 60 and older community dwelling women 1 yr since last menses Exclusion Criteria: Medications: Oral glucocorticoids for > 10 days in the last 3 months Cortef (hydrocortisone) Prednisone Parenteral glucocorticoids • Decadron (dexamethasone) Osteoporosis medications in the last 6 months Forteo (teriparatide) Calcimar, Miacalcin (calcitonin) Evista (raloxifene) Osteoporosis medications in the last 2 years Fosamax (alendronate) Didronel (etidronate) Aredia (pamidronate) Actonel (risedronate) Reclast (zoledronate) Tamoxifen in the last 6 months Calcium/Parathyroid Rocaltrol (calcitriol) Zemplar (paricalcitol) Drisdol, Ergocalciferol Diuretics currently hydrocholorothiazide (HCTZ) Diuril (chlorothiazide) Thalitone (chlorthalidone) Zaroxolyn (metolazone) Dyazide Maxide Moduretic Lasix (forosamine) Dyrenium (triamterene) Midamor Testosterone or estrogen in the last 6 months (vaginal estrogen okay) Angiotensin converting enzyme (ACE) inhibitors currently Benazepril (Lotensin) Captopril (Capoten) Enalapril (Vasotec) Fosinopril (Monopril) Lisinopril (Prinivil, Zestril) Moexipril (Univasc) Perindopril (Aceon) Quinapril (Accupril) Ramipril (Altace) Trandolapril (Mavik) Angiotensin II receptor blockers currently Candesartan (Atacand) Eprosartan (Teveten) Irbesartan (Avapro) Losartan (Cozaar) Olmesartan (Benicar) Telmisartan (Micardis) Valsartan (Diovan) Over-the-Counter Drugs currently Antacids - any antacid that contains calcium carbonate, aluminum hydroxide, magnesium hydroxide, or calcium acetate - selected examples include TUMS Mylanta Maalox Titralac Rolaids Sodium bicarbonate (baking soda) Note: magaldrate or Riopan® is allowed Potassium supplements Salt substitutes Conditions/Diseases renal disease including kidney stones in the past 5 years or glomerular filtration rate (GFR) < 60 ml/min/1.73 m2 hyperkalemia (serum potassium >5.3 meq/L; normal range 3.5-5.3 meq/L) elevated serum bicarbonate (serum bicarbonate > 29 mmol/L; normal range 22-29 mmol/L) cirrhosis gastroesophageal reflux disease (GERD) requiring treatment with alkali-containing antacids (TUMS, Mylanta, Maalox, Titralac, Rolaids, or sodium bicarbonate) hyperparathyroidism untreated thyroid disease significant immune disorder such as rheumatoid arthritis current unstable heart disease active malignancy or cancer therapy in the last year fasting spot urine calcium/creatinine > 0.38 mmol/mmol after 1 wk off of calcium supplements congestive heart failure, arrhythmias (surgically treated arrhythmias acceptable), or myocardial infarction in last 12 months serum calcium outside the normal range of 8.3-10.2 mg/dl uncontrolled diabetes mellitus (fasting blood sugar > 130) alcohol use exceeding 2 drinks/day peptic ulcers or esophageal stricture weight <45 or >113.5 kg (<99 or >249.7 lbs) other abnormalities in screening labs, at discretion of the study physician (the PI)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bess Dawson-Hughes, M.D.
Organizational Affiliation
Tufts University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29211866
Citation
Shea MK, Dawson-Hughes B. Association of Urinary Citrate With Acid-Base Status, Bone Resorption, and Calcium Excretion in Older Men and Women. J Clin Endocrinol Metab. 2018 Feb 1;103(2):452-459. doi: 10.1210/jc.2017-01778.
Results Reference
derived
PubMed Identifier
28842733
Citation
Ceglia L, Dawson-Hughes B. Increasing alkali supplementation decreases urinary nitrogen excretion when adjusted for same day nitrogen intake. Osteoporos Int. 2017 Dec;28(12):3355-3359. doi: 10.1007/s00198-017-4196-8. Epub 2017 Aug 25.
Results Reference
derived

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Musculoskeletal Effects of Bicarbonate

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