Muscle LossPhase 2NCT01475214
Musculoskeletal Effects of Bicarbonate
A Phase 2 study testing potassium bicarbonate in people with Muscle Loss and Fractures, run by Tufts University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Muscle Loss, Fractures, Osteoporosis, Age Related
- What is being tested?
- potassium bicarbonate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 244 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to Aug 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- men and women
- age 60 and older
- community dwelling
- women 1 yr since last menses
Who cannot join
- Medications:
- Oral glucocorticoids for > 10 days in the last 3 months
- Cortef (hydrocortisone)
- Prednisone
- Parenteral glucocorticoids
- Decadron (dexamethasone)
Show all 82Show fewer
- 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) < 60 ml/min/1.73 m2
- hyperkalemia (serum potassium >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 <45 or >113.5 kg (<99 or >249.7 lbs)
- other abnormalities in screening labs, at discretion of the study physician (the PI)
Trial locations and contacts
1 site in 1 country.
United States1 site
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University
Boston, Massachusetts, 02111
About this study
Official title: 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.
Read the 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.
- Conditions
- Muscle Loss, Fractures, Osteoporosis, Age Related, Fall Injury
- Being tested
- potassium bicarbonate, Inactive placebo capsule
- Keywords
- potassium bicarbonate, urinary N-telopeptide, urinary nitrogen, net acid excretion
- Medical subject headings
- Muscular Atrophy, Fractures, Bone, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
potassium bicarbonateDietary supplement
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 bicarbonateDietary supplement
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
Inactive placebo capsuleOther
microcrystalline cellulose
| Study group | Role | What they receive |
|---|---|---|
| potassium bicarbonate low dose | 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 Receives: Dietary Supplement: potassium bicarbonate |
| potassium bicarbonate higher dose | 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 Receives: Dietary Supplement: potassium bicarbonate |
| placebo | Placebo comparator | microcrystalline cellulose Receives: Other: Inactive placebo capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 84 days
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.
Measured: 84 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2011 (estimated)
- Study startJan 2012
- Primary completionDec 2014
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Muscle LossStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 244 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Principal investigator, Bess Dawson-Hughes, Tufts University
- Investigators
- Bess Dawson-Hughes, M.D., Principal investigator, Tufts University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01475214
- Sponsor's protocol ID
- 2705
- Other IDs
- R01AR060261
- Status last verified
- Sep 2015
- First submitted
- 16 Nov 2011
- Last updated
- 19 Oct 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Shea MK, Dawson-Hughes B. Association of Urinary Citrate With Acid-Base Status, Bone Resorption, and Calcium Excretion in Older Men and Women. J Clin Endocrinol Metab. 2018 Feb 1;103(2):452-459. doi: 10.1210/jc.2017-01778.
PubMed 29211866Ceglia L, Dawson-Hughes B. Increasing alkali supplementation decreases urinary nitrogen excretion when adjusted for same day nitrogen intake. Osteoporos Int. 2017 Dec;28(12):3355-3359. doi: 10.1007/s00198-017-4196-8. Epub 2017 Aug 25.
PubMed 28842733
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Musculoskeletal Benefits of Bicarbonate in Older Adults - A Dose-Finding Trial
- ClinicalTrials.gov ID
- NCT01475214
- Acronym / sponsor ID
- 2705
- Conditions
- Muscle Loss, Fractures, Osteoporosis, Age Related, Fall Injury
- Keywords
- potassium bicarbonate, urinary N-telopeptide, urinary nitrogen, net acid excretion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 244 participants (actual)
- Lead sponsor
- Tufts UniversityUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- Jan 2012
- Primary completion
- Dec 2014 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 21 Nov 2011 (estimated)
- Results
- Posted 19 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| potassium bicarbonate low dose | Active comparator | Dietary Supplement: potassium bicarbonatepotassium 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 higher dose | Active comparator | Dietary Supplement: potassium bicarbonatepotassium 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 | Placebo comparator | Other: Inactive placebo capsulemicrocrystalline cellulose |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- men and women
- age 60 and older
- community dwelling
- women 1 yr since last menses
Key exclusion criteria (82 listed)
- Oral glucocorticoids for > 10 days in the last 3 months
- Parenteral glucocorticoids
- Osteoporosis medications in the last 6 months
- Osteoporosis medications in the last 2 years
- Tamoxifen in the last 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| potassium bicarbonatepotassium 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 low dose |
| potassium bicarbonatepotassium bicarbonate in dose of 1.5 mmol/kg per day, given in three even daily doses after meals with a full glass of water | Dietary supplement | potassium bicarbonate higher dose |
| Inactive placebo capsulemicrocrystalline cellulose | Other | placebo |
Primary outcome
The Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptide
Time frame: 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
Time frame: 84 days
Describe and compare changes in 24-hour urinary nitrogen in the low and high dose and KHCO3 group and in placebo.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29211866Shea MK, Dawson-Hughes B. Association of Urinary Citrate With Acid-Base Status, Bone Resorption, and Calcium Excretion in Older Men and Women. J Clin Endocrinol Metab. 2018 Feb 1;103(2):452-459. doi: 10.1210/jc.2017-01778.
- Derived from this study: PubMed 28842733Ceglia L, Dawson-Hughes B. Increasing alkali supplementation decreases urinary nitrogen excretion when adjusted for same day nitrogen intake. Osteoporos Int. 2017 Dec;28(12):3355-3359. doi: 10.1007/s00198-017-4196-8. Epub 2017 Aug 25.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bess Dawson-Hughes, M.D. principal investigator
Tufts University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing potassium bicarbonate in people with Muscle Loss and Fractures, run by Tufts University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 82 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptide (time frame: 84 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01475214, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2015.