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Musculoskeletal Effects of Bicarbonate

Musculoskeletal Benefits of Bicarbonate in Older Adults - A Dose-Finding Trial

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01475214
Enrollment
244
Registered
2011-11-21
Start date
2012-01-31
Completion date
2015-08-31
Last updated
2015-10-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

potassium bicarbonate, urinary N-telopeptide, urinary nitrogen, net acid excretion

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.

Interventions

DIETARY_SUPPLEMENTpotassium 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

microcrystalline cellulose

Sponsors

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
CollaboratorNIH
Tufts University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes

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 (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)

Design outcomes

Primary

MeasureTime frameDescription
The Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptide84 daysDescribe 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 Nitrogen84 daysDescribe and compare changes in 24-hour urinary nitrogen in the low and high dose and KHCO3 group and in placebo.

Countries

United States

Participant flow

Participants by arm

ArmCount
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 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
84
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 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
79
Inactive Placebo Capsule
microcrystalline cellulose placebo: microcrystalline cellulose
81
Total244

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Overall StudyLost to Follow-up101
Overall StudyPhysician Decision200
Overall StudyWithdrawal by Subject241

Baseline characteristics

CharacteristicTotalInactive Placebo CapsulePotassium Bicarbonate Higher DosePotassium Bicarbonate Low Dose
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
123 Participants40 Participants39 Participants44 Participants
Age, Categorical
Between 18 and 65 years
121 Participants41 Participants40 Participants40 Participants
Age, Continuous66.9 years
STANDARD_DEVIATION 5.6
66.8 years
STANDARD_DEVIATION 6.1
66.4 years
STANDARD_DEVIATION 5.1
67.4 years
STANDARD_DEVIATION 5.5
Glomerular Filtration Rate (GFR)76.3 ml/min/1.73m^2
STANDARD_DEVIATION 13
74.8 ml/min/1.73m^2
STANDARD_DEVIATION 12.9
77.5 ml/min/1.73m^2
STANDARD_DEVIATION 12.8
76.5 ml/min/1.73m^2
STANDARD_DEVIATION 13.2
Race/Ethnicity, Customized
African-American
18 participants3 participants9 participants6 participants
Race/Ethnicity, Customized
Asian
2 participants1 participants1 participants0 participants
Race/Ethnicity, Customized
Caucasian, Hispanic
5 participants2 participants1 participants2 participants
Race/Ethnicity, Customized
Caucasian, Non-hispanic
219 participants75 participants68 participants76 participants
Region of Enrollment
United States
244 participants81 participants79 participants84 participants
Serum bicarbonate26.0 mmol/L
STANDARD_DEVIATION 2.2
26.1 mmol/L
STANDARD_DEVIATION 2.4
25.8 mmol/L
STANDARD_DEVIATION 2.4
26.1 mmol/L
STANDARD_DEVIATION 1.9
Serum potassium4.33 meq/L
STANDARD_DEVIATION 0.32
4.30 meq/L
STANDARD_DEVIATION 0.31
4.39 meq/L
STANDARD_DEVIATION 0.36
4.31 meq/L
STANDARD_DEVIATION 0.29
Sex: Female, Male
Female
118 Participants38 Participants39 Participants41 Participants
Sex: Female, Male
Male
126 Participants43 Participants40 Participants43 Participants
Urine calcium/creatinine104 mg/g
STANDARD_DEVIATION 55
114 mg/g
STANDARD_DEVIATION 69
99 mg/g
STANDARD_DEVIATION 48
99 mg/g
STANDARD_DEVIATION 43
Weight74.1 kg
STANDARD_DEVIATION 13.6
73.2 kg
STANDARD_DEVIATION 14
74.2 kg
STANDARD_DEVIATION 13
74.8 kg
STANDARD_DEVIATION 13.7

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
19 / 8429 / 7923 / 81
serious
Total, serious adverse events
3 / 843 / 791 / 81

Outcome results

Primary

Co-primary Aim - to Identify the Dose of KHCO3 Needed for Maximal Suppression of 24-hr Urinary Nitrogen

Describe and compare changes in 24-hour urinary nitrogen in the low and high dose and KHCO3 group and in placebo.

Time frame: 84 days

Population: healthy men and women age 60 years and older

ArmMeasureGroupValue (MEAN)Dispersion
Potassium Bicarbonate Low DoseCo-primary Aim - to Identify the Dose of KHCO3 Needed for Maximal Suppression of 24-hr Urinary Nitrogenbaseline 24-hr urine nitrogen769 mmol/dayStandard Error 32
Potassium Bicarbonate Low DoseCo-primary Aim - to Identify the Dose of KHCO3 Needed for Maximal Suppression of 24-hr Urinary Nitrogenchange in 24-hr urine nitrogen-29.4 mmol/dayStandard Error 18.6
Potassium Bicarbonate Higher DoseCo-primary Aim - to Identify the Dose of KHCO3 Needed for Maximal Suppression of 24-hr Urinary Nitrogenbaseline 24-hr urine nitrogen834 mmol/dayStandard Error 39
Potassium Bicarbonate Higher DoseCo-primary Aim - to Identify the Dose of KHCO3 Needed for Maximal Suppression of 24-hr Urinary Nitrogenchange in 24-hr urine nitrogen-16.4 mmol/dayStandard Error 19.1
Inactive Placebo CapsuleCo-primary Aim - to Identify the Dose of KHCO3 Needed for Maximal Suppression of 24-hr Urinary Nitrogenbaseline 24-hr urine nitrogen864 mmol/dayStandard Error 33
Inactive Placebo CapsuleCo-primary Aim - to Identify the Dose of KHCO3 Needed for Maximal Suppression of 24-hr Urinary Nitrogenchange in 24-hr urine nitrogen-21.0 mmol/dayStandard Error 18.7
Primary

The Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptide

Describe and compare changes in urinary N-telopeptide (NTX) across the placebo and Potassium Bicarbonate (KHCO3) doses.

Time frame: 84 days

Population: Healthy men and women age 60 years and older

ArmMeasureGroupValue (MEAN)Dispersion
Potassium Bicarbonate Low DoseThe Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptidebaseline 24-hr urinary NTX240 nmol/dayStandard Error 17
Potassium Bicarbonate Low DoseThe Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptidechange in NTX-53 nmol/dayStandard Error 11
Potassium Bicarbonate Higher DoseThe Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptidebaseline 24-hr urinary NTX230 nmol/dayStandard Error 20
Potassium Bicarbonate Higher DoseThe Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptidechange in NTX-43 nmol/dayStandard Error 11
Inactive Placebo CapsuleThe Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptidebaseline 24-hr urinary NTX241 nmol/dayStandard Error 17
Inactive Placebo CapsuleThe Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptidechange in NTX-14 nmol/dayStandard Error 11

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026