Phase 2 N=244 Randomized Double-blind Prevention

Musculoskeletal Effects of Bicarbonate

Muscle Loss · Fractures · Osteoporosis, Age Related · Fall Injury

Bottom Line

View on ClinicalTrials.gov: NCT01475214 ↗

Enrolled (actual)

244

Serious AEs

2.9%

Results posted

Oct 2015

Primary outcome: Primary: The Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptide — 240; 230; 241; -53 nmol/day

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: potassium bicarbonate (Dietary_supplement); Inactive placebo capsule (Other)
Age: Adult, Older Adult · 60+ yrs
Sex: All
Sponsor: Tufts University
Primary completion: Dec 2014

Outcome Measures

Outcome	Result	p-value
PRIMARY The Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptide	240; 230; 241; -53; -43; -14	—
PRIMARY Co-primary Aim - to Identify the Dose of KHCO3 Needed for Maximal Suppression of 24-hr Urinary Nitrogen	769; 834; 864; -29.4; -16.4; -21.0	—

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.

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) 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 113.5 kg ( 249.7 lbs)
other abnormalities in screening labs, at discretion of the study physician (the PI)

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01475214). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.