Musculoskeletal Effects of Bicarbonate

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Tufts University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Bess Dawson-Hughes, Tufts University
ClinicalTrials.gov Identifier:
NCT01475214
First received: November 16, 2011
Last updated: October 23, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Age-related Bone Loss
Age Related Muscle Loss
Falls
Fractures
Dietary Supplement: potassium bicarbonate
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Musculoskeletal Benefits of Bicarbonate in Older Adults - A Dose-Finding Trial

Resource links provided by NLM:


Further study details as provided by Tufts University:

Primary Outcome Measures:
  • The primary aim is to identify the dose of KHCO3 needed for maximal suppression of 24-hr urinary N-telopeptide/creatinine ratio [ Time Frame: 9/11-12/14 (up to 4 years) ] [ Designated as safety issue: No ]
    Describe and compare changes in urinary N-telopeptide across the placebo and KHCO3 doses.


Secondary Outcome Measures:
  • The secondary aim is to identify the dose of KHCO3 needed for maximal suppression of 24-hr urinary nitrogen/creatinine ratio [ Time Frame: 9/11-11/14 (up to 4 years) ] [ Designated as safety issue: No ]
    Describe and compare changes in urinary nitrogen across the placebo and KHCO3 doses.


Estimated Enrollment: 276
Study Start Date: January 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: potassium bicarbonate low dose
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
Dietary Supplement: potassium bicarbonate
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
Active Comparator: potassium bicarbonate higher dose
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
Dietary Supplement: potassium bicarbonate
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
Placebo Comparator: inactive capsule
microcrystalline cellulose
Other: placebo
microcrystalline cellulose

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.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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 (furosamine)
    • 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 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. 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01475214

Contacts
Contact: Nancy J. Palermo, B.S. 6175563073 nancy.palermo@tufts.edu
Contact: Bess Dawson-Hughes, M.D. 6175563066 bess.dawson-hughes@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: Nancy J. Palermo, B.S.    617-556-3073    nancy.palermo@tufts.edu   
Contact: Bess Dawson-Hughes, M.D.    6175563066    bess.dawson-hughes@tufts.edu   
Principal Investigator: Bess Dawson-Hughes, M.D.         
Sponsors and Collaborators
Tufts University
Investigators
Principal Investigator: Bess Dawson-Hughes, M.D. Tufts University
  More Information

No publications provided

Responsible Party: Bess Dawson-Hughes, Professor of Medicine, Tufts University
ClinicalTrials.gov Identifier: NCT01475214     History of Changes
Other Study ID Numbers: 2705, R01AR060261, RO1AR060261
Study First Received: November 16, 2011
Last Updated: October 23, 2013
Health Authority: United States: Federal Government

Keywords provided by Tufts University:
potassium bicarbonate
urinary N-telopeptide
urinary nitrogen
net acid excretion

Additional relevant MeSH terms:
Osteoporosis
Fractures, Bone
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Wounds and Injuries

ClinicalTrials.gov processed this record on August 28, 2014