Overview

This trial is active, not recruiting.

Conditions age-related bone loss, age related muscle loss, falls, fractures
Treatments potassium bicarbonate, placebo
Phase phase 2
Sponsor Tufts University
Collaborator National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Start date January 2012
End date December 2014
Trial size 276 participants
Trial identifier NCT01475214, 2705, R01AR060261, RO1AR060261

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose prevention
Arm
(Active Comparator)
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
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 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
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)
microcrystalline cellulose
placebo
microcrystalline cellulose

Primary Outcomes

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)

Secondary Outcomes

Measure
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)

Eligibility Criteria

Male or female participants at least 60 years old.

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)

Additional Information

Official title Musculoskeletal Benefits of Bicarbonate in Older Adults - A Dose-Finding Trial
Principal investigator Bess Dawson-Hughes, M.D.
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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2015.
Information provided to ClinicalTrials.gov by Tufts University.