Musculoskeletal Effects of Bicarbonate

NCT01475214 | Completed Phase 2 Results

• 2 other identifiers: 2705R01AR060261
• Study Type: interventional
• Target: 244
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  84 days

Study Arms (3)

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

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

Dietary Supplement: potassium bicarbonate

placebo

PLACEBO COMPARATOR

microcrystalline cellulose

Other: Inactive placebo capsule

Interventions

potassium bicarbonate DIETARY_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 bicarbonate low dose

Inactive placebo capsule OTHER

microcrystalline cellulose

placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Tufts University: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University

Boston, Massachusetts, 02111, United States

Location

Related Publications (2)

• 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.

  PMID: 29211866 DERIVED

• Ceglia 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.

  PMID: 28842733 DERIVED

MeSH Terms

Conditions

Muscular Atrophy; Fractures, Bone; Osteoporosis

Interventions

potassium bicarbonate

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Wounds and Injuries; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Dr. Bess Dawson-Hughes
• Organization: Jean Mayer Human Nutrition Research Center on Aging at Tufts University

bess.dawson-hughes@tufts.edu

617-556-3066

Study Officials

• Bess Dawson-Hughes, M.D.

  Tufts University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: November 16, 2011
• First Posted: November 21, 2011
• Study Start: January 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: August 1, 2015
• Last Updated: October 19, 2015
• Results First Posted: October 19, 2015

Record last verified: 2015-09

Locations

US (1)