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

November 16, 2011
October 23, 2013
January 2012
December 2014   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01475214 on ClinicalTrials.gov Archive Site
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.
Same as current
Not Provided
Not Provided
 
Musculoskeletal Effects of Bicarbonate
Musculoskeletal Benefits of Bicarbonate in Older Adults - A Dose-Finding Trial

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
  • Age-related Bone Loss
  • Age Related Muscle Loss
  • Falls
  • Fractures
  • 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
  • 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
  • Other: placebo
    microcrystalline cellulose
  • 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
    Intervention: Dietary Supplement: potassium bicarbonate
  • 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
    Intervention: Dietary Supplement: potassium bicarbonate
  • Placebo Comparator: inactive capsule
    microcrystalline cellulose
    Intervention: Other: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
276
August 2015
December 2014   (final data collection date for primary outcome measure)

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)
Both
60 Years and older
Yes
Contact: Nancy J. Palermo, B.S. 6175563073 nancy.palermo@tufts.edu
Contact: Bess Dawson-Hughes, M.D. 6175563066 bess.dawson-hughes@tufts.edu
United States
 
NCT01475214
2705, R01AR060261, RO1AR060261
No
Bess Dawson-Hughes, Tufts University
Tufts University
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Principal Investigator: Bess Dawson-Hughes, M.D. Tufts University
Tufts University
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP