Musculoskeletal Effects of Bicarbonate

Phase 2

Completed

• Conditions: Osteoporosis, Age Related; Fall Injury; Fractures; Muscle Loss
• Interventions: Other: Inactive placebo capsule; Dietary Supplement: potassium bicarbonate

• Registration Number: NCT01475214
• Lead Sponsor: Tufts University

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.

Study Timeline

• Study First Submitted: 2011-11-16
• Study First Submitted QC: 2011-11-18
• Study First Posted: 2011-11-21
• Study Start: 2012-01
• Primary Completion: 2014-12
• Results First Submitted: 2015-06-10
• Study Completion: 2015-08
• Status Verified: 2015-09
• Results First Submitted QC: 2015-09-18
• Last Update Submitted: 2015-09-18
• Results First Posted: 2015-10-19
• Last Update Posted: 2015-10-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 244

Inclusion Criteria

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Inactive placebo capsule	microcrystalline cellulose
potassium bicarbonate higher dose	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
potassium bicarbonate low dose	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

Primary Outcome Measures

Name	Time	Method
The Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptide	84 days	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	84 days	Describe and compare changes in 24-hour urinary nitrogen in the low and high dose and KHCO3 group and in placebo.

Trial Locations

Locations (1)

Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University; 🇺🇸 Boston, Massachusetts, United States