Veverimer to Decrease Net Acid Excretion and Bone Resorption in Adults With Osteopenia

NCT07473713 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY000065571R61AR085647-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if veverimer will reduce urinary net acid excretion leading to reduced bone resorption in healthy adults with osteopenia. The main questions it aims to answer are:

• How much does each dose of veverimer (vs. placebo) reduce 24-hr urinary net acid excretion.
• Describe the safety of veverimer based on changes in serum bicarbonate and potassium.
• Assess the changes in bone resorption.
• Assess the changes in bone formation.
• Explore the effect of veverimer on physical performance. Participants will:
• Take veverimer or placebo every day or every other day for 8 weeks
• Visit the clinic a total of 8 times (including screening) for checkups and testing
• Keep a medication diary tracking each day they take the study drug

Conditions

Osteopenia

Keywords

Osteopenia; veverimer

Outcome Measures

Primary Outcomes (1)

• 24-hr urinary net acid excretion

  measured at screening, week 2, week 8 and week 8 +1day

Secondary Outcomes (4)

• Serum bicarbonate level

  measured at screening, week 0, week 1, week 2, week 4, week 8

• Serum potassium level

  measured at screening, week 0, week 1, week 2, week 4, week 8

• Serum C-telopeptide level

  measured at week 0, week 2, week 8

• Serum procollagen type 1 N-propeptide level

  measured at week 0 and week 8

Other Outcomes (5)

• Sit-to-stand time

  measured at week 0 and week 8

• Gait speed

  measured at week 0 and week 8

• Time-up-and-go time

  measured at week 0 and week 8

Study Arms (3)

Veverimer 9 g/day

EXPERIMENTAL

Drug: veverimer daily

Veverimer 9 g/every other day

EXPERIMENTAL

Drug: veverimer every other day

Placebo (microcrystalline cellulose with 0.075% yellow ferric oxide)

PLACEBO COMPARATOR

Other: Placebo

Interventions

veverimer daily DRUG

8 weeks of taking 9 grams of veverimer (a powder mixed into water) daily

Veverimer 9 g/day

veverimer every other day DRUG

8 weeks of taking 9 grams of veverimer (a powder mixed into water) every other day

Veverimer 9 g/every other day

Placebo OTHER

8 weeks taking 9 grams microcrystalline cellulose (powdered mixed into water) daily or every other day

Placebo (microcrystalline cellulose with 0.075% yellow ferric oxide)

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Community dwelling adults age 50 years and older (approximately equal numbers of men and women).
• Men should be sterile or agree to use contraception throughout the study.
• Women must be postmenopausal, defined as no menses in the last 5 years (to reduce variability in change in bone resorption since menopause prompts a rapid increase in bone resorption).
• Osteopenia will be defined as a bone mineral density (BMD) T-score at the lumbar spine, femoral neck, or total hip lower than -1 or higher than -2.5.
• On a prescreening interview, candidates must report a usual diet associated with an acid load by our validated short questionnaire.
• Estimated glomerular filtration rate (eGFR) must be 45 ml/min or greater.
• Participants must agree not to change their exercise pattern or medication use during the study.
• Participants must agree not to change their pattern of supplement use and not to use antacids during the study because most calcium supplements and other antacids add alkali.
• Participants must agree to not change their eating habits or intentionally change their weight.

You may not qualify if:

• Normal BMD T-scores at all spine and hip sites, osteoporosis based on BMD T-score of -2.5 or less
• Respiratory illness in last month
• Chronic obstructive pulmonary disease (COPD)
• Asthma
• Nausea/vomiting in last month
• Dysphagia
• Malabsorption
• Inflammatory bowel disease
• Chronic diarrhea (defined as loose bowel movements daily) or constipation (≤ 2 stools per week)
• Insulin-requiring diabetes or fasting plasma glucose \>125 mg/dl
• Untreated thyroid disease
• Cirrhosis
• Current unstable heart disease
• Malignancy (except non-melanoma skin cancer) or cancer therapy in last year
• Alcohol use \>2 drinks/day.

Sponsors & Collaborators

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

Study Sites (1)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Related Publications (43)

• Dawson-Hughes B, Castaneda-Sceppa C, Harris SS, Palermo NJ, Cloutier G, Ceglia L, Dallal GE. Impact of supplementation with bicarbonate on lower-extremity muscle performance in older men and women. Osteoporos Int. 2010 Jul;21(7):1171-9. doi: 10.1007/s00198-009-1049-0. Epub 2009 Sep 1.

  PMID: 19727904 BACKGROUND

• Bauer DC, Garnero P, Bilezikian JP, Greenspan SL, Ensrud KE, Rosen CJ, Palermo L, Black DM. Short-term changes in bone turnover markers and bone mineral density response to parathyroid hormone in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2006 Apr;91(4):1370-5. doi: 10.1210/jc.2005-1712. Epub 2006 Jan 31.

  PMID: 16449339 BACKGROUND

• Chen P, Satterwhite JH, Licata AA, Lewiecki EM, Sipos AA, Misurski DM, Wagman RB. Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis. J Bone Miner Res. 2005 Jun;20(6):962-70. doi: 10.1359/JBMR.050105. Epub 2005 Jan 18.

  PMID: 15883636 BACKGROUND

• Niimi R, Kono T, Nishihara A, Hasegawa M, Matsumine A, Nakamura T, Kono T, Sudo A. An algorithm using the early changes in PINP to predict the future BMD response for patients treated with daily teriparatide. Osteoporos Int. 2014 Jan;25(1):377-84. doi: 10.1007/s00198-013-2426-2. Epub 2013 Jun 29.

  PMID: 23812597 BACKGROUND

• Kotlarczyk MP, Perera S, Resnick NM, Nace DA, Greenspan SL. Early changes in bone turnover predict longer-term changes in bone mineral density but not trabecular bone score in frail older women. Arch Osteoporos. 2020 May 26;15(1):79. doi: 10.1007/s11657-020-00749-w.

  PMID: 32458096 BACKGROUND

• Vasikaran S, Eastell R, Bruyere O, Foldes AJ, Garnero P, Griesmacher A, McClung M, Morris HA, Silverman S, Trenti T, Wahl DA, Cooper C, Kanis JA; IOF-IFCC Bone Marker Standards Working Group. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int. 2011 Feb;22(2):391-420. doi: 10.1007/s00198-010-1501-1. Epub 2010 Dec 24.

  PMID: 21184054 BACKGROUND

• Jajoo R, Song L, Rasmussen H, Harris SS, Dawson-Hughes B. Dietary acid-base balance, bone resorption, and calcium excretion. J Am Coll Nutr. 2006 Jun;25(3):224-30. doi: 10.1080/07315724.2006.10719536.

  PMID: 16766781 BACKGROUND

• JORGENSEN K. Titrimetric determination of the net excretion of acid/base in urine. Scand J Clin Lab Invest. 1957;9(3):287-91. doi: 10.3109/00365515709079972. No abstract available.

  PMID: 13495348 BACKGROUND

• Shea MK, Gilhooly CH, Dawson-Hughes B. Food groups associated with measured net acid excretion in community-dwelling older adults. Eur J Clin Nutr. 2017 Mar;71(3):420-424. doi: 10.1038/ejcn.2016.195. Epub 2016 Oct 19.

  PMID: 27759073 BACKGROUND

• Parsell D, Shao J, Guttendorf R, Mathur V, Li E, Wu YS, Tsao L, Tabakman S, Stasiv Y, Lee A, Biyani K, Klaerner G. Assessment of the Potential for Veverimer Drug-Drug Interactions. Drug Metab Dispos. 2021 Jul;49(7):490-500. doi: 10.1124/dmd.121.000366. Epub 2021 May 24.

  PMID: 34031138 BACKGROUND

• Frick KK, Krieger NS, Nehrke K, Bushinsky DA. Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1. J Bone Miner Res. 2009 Feb;24(2):305-13. doi: 10.1359/jbmr.081015.

  PMID: 18847331 BACKGROUND

• Tomura H, Mogi C, Sato K, Okajima F. Proton-sensing and lysolipid-sensitive G-protein-coupled receptors: a novel type of multi-functional receptors. Cell Signal. 2005 Dec;17(12):1466-76. doi: 10.1016/j.cellsig.2005.06.002.

  PMID: 16014326 BACKGROUND

• Ludwig MG, Vanek M, Guerini D, Gasser JA, Jones CE, Junker U, Hofstetter H, Wolf RM, Seuwen K. Proton-sensing G-protein-coupled receptors. Nature. 2003 Sep 4;425(6953):93-8. doi: 10.1038/nature01905.

  PMID: 12955148 BACKGROUND

• Arnett TR, Dempster DW. Effect of pH on bone resorption by rat osteoclasts in vitro. Endocrinology. 1986 Jul;119(1):119-24. doi: 10.1210/endo-119-1-119.

  PMID: 3720660 BACKGROUND

• Komarova SV, Pereverzev A, Shum JW, Sims SM, Dixon SJ. Convergent signaling by acidosis and receptor activator of NF-kappaB ligand (RANKL) on the calcium/calcineurin/NFAT pathway in osteoclasts. Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2643-8. doi: 10.1073/pnas.0406874102. Epub 2005 Feb 4.

  PMID: 15695591 BACKGROUND

• Bushinsky DA, Krieger NS. Effects of acid on bone. Kidney Int. 2022 Jun;101(6):1160-1170. doi: 10.1016/j.kint.2022.02.032. Epub 2022 Mar 26.

  PMID: 35351460 BACKGROUND

• Ceglia L, Shea K, Rasmussen H, Gilhooly CH, Dawson-Hughes B. A Randomized Study on the Effect of Dried Fruit on Acid-Base Balance, Diet Quality, and Markers of Musculoskeletal Health in Community Dwelling Adults. J Am Nutr Assoc. 2023 Jul;42(5):476-483. doi: 10.1080/27697061.2022.2082599. Epub 2022 Jul 11.

  PMID: 35815972 BACKGROUND

• Kaesler N, Baid-Agrawal S, Grams S, Nadal J, Schmid M, Schneider MP, Eckardt KU, Floege J, Bergmann MM, Schlieper G, Saritas T. Low adherence to CKD-specific dietary recommendations associates with impaired kidney function, dyslipidemia, and inflammation. Eur J Clin Nutr. 2021 Sep;75(9):1389-1397. doi: 10.1038/s41430-020-00849-3. Epub 2021 Feb 2.

  PMID: 33531632 BACKGROUND

• Remer T, Manz F. Potential renal acid load of foods and its influence on urine pH. J Am Diet Assoc. 1995 Jul;95(7):791-7. doi: 10.1016/S0002-8223(95)00219-7.

  PMID: 7797810 BACKGROUND

• Frassetto L, Morris RC Jr, Sebastian A. Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal women. J Clin Endocrinol Metab. 1997 Jan;82(1):254-9. doi: 10.1210/jcem.82.1.3663.

  PMID: 8989270 BACKGROUND

• Frassetto LA, Todd KM, Morris RC Jr, Sebastian A. Estimation of net endogenous noncarbonic acid production in humans from diet potassium and protein contents. Am J Clin Nutr. 1998 Sep;68(3):576-83. doi: 10.1093/ajcn/68.3.576.

  PMID: 9734733 BACKGROUND

• Frassetto L, Morris RC Jr, Sellmeyer DE, Todd K, Sebastian A. Diet, evolution and aging--the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet. Eur J Nutr. 2001 Oct;40(5):200-13. doi: 10.1007/s394-001-8347-4.

  PMID: 11842945 BACKGROUND

• Dawson-Hughes B. Acid-base balance of the diet-implications for bone and muscle. Eur J Clin Nutr. 2020 Aug;74(Suppl 1):7-13. doi: 10.1038/s41430-020-0691-7.

  PMID: 32873951 BACKGROUND

• Berkemeyer S, Vormann J, Gunther AL, Rylander R, Frassetto LA, Remer T. Renal net acid excretion capacity is comparable in prepubescence, adolescence, and young adulthood but falls with aging. J Am Geriatr Soc. 2008 Aug;56(8):1442-8. doi: 10.1111/j.1532-5415.2008.01799.x.

  PMID: 18808599 BACKGROUND

• Frassetto L, Sebastian A. Age and systemic acid-base equilibrium: analysis of published data. J Gerontol A Biol Sci Med Sci. 1996 Jan;51(1):B91-9. doi: 10.1093/gerona/51a.1.b91.

  PMID: 8548506 BACKGROUND

• Frassetto LA, Morris RC Jr, Sebastian A. Effect of age on blood acid-base composition in adult humans: role of age-related renal functional decline. Am J Physiol. 1996 Dec;271(6 Pt 2):F1114-22. doi: 10.1152/ajprenal.1996.271.6.F1114.

  PMID: 8997384 BACKGROUND

• Wesson DE, Buysse JM, Bushinsky DA. Mechanisms of Metabolic Acidosis-Induced Kidney Injury in Chronic Kidney Disease. J Am Soc Nephrol. 2020 Mar;31(3):469-482. doi: 10.1681/ASN.2019070677. Epub 2020 Jan 27.

  PMID: 31988269 BACKGROUND

• Becker DJ, Kilgore ML, Morrisey MA. The societal burden of osteoporosis. Curr Rheumatol Rep. 2010 Jun;12(3):186-91. doi: 10.1007/s11926-010-0097-y.

  PMID: 20425518 BACKGROUND

• Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007 Mar;22(3):465-75. doi: 10.1359/jbmr.061113.

  PMID: 17144789 BACKGROUND

• LeBoff MS, Greenspan SL, Insogna KL, Lewiecki EM, Saag KG, Singer AJ, Siris ES. The clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int. 2022 Oct;33(10):2049-2102. doi: 10.1007/s00198-021-05900-y. Epub 2022 Apr 28.

  PMID: 35478046 BACKGROUND

• Sarafrazi N, Wambogo EA, Shepherd JA. Osteoporosis or Low Bone Mass in Older Adults: United States, 2017-2018. NCHS Data Brief. 2021 Mar;(405):1-8.

  PMID: 34029181 BACKGROUND

• Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int. 1994 Nov;4(6):368-81. doi: 10.1007/BF01622200.

  PMID: 7696835 BACKGROUND

• Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, Genant HK, Palermo L, Scott J, Vogt TM. Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group. Lancet. 1993 Jan 9;341(8837):72-5. doi: 10.1016/0140-6736(93)92555-8.

  PMID: 8093403 BACKGROUND

• Tangri N, Mathur VS, Bushinsky DA, Klaerner G, Li E, Parsell D, Stasiv Y, Walker M, Wesson DE, Wheeler DC, Perkovic V, Inker LA. VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of CKD in Patients with Metabolic Acidosis. J Am Soc Nephrol. 2024 Mar 1;35(3):311-320. doi: 10.1681/ASN.0000000000000292. Epub 2024 Jan 23.

  PMID: 38261535 BACKGROUND

• Wesson DE, Mathur V, Tangri N, Stasiv Y, Parsell D, Li E, Klaerner G, Bushinsky DA. Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: a multicentre, randomised, double-blind, controlled, phase 3 trial. Lancet. 2019 Apr 6;393(10179):1417-1427. doi: 10.1016/S0140-6736(18)32562-5. Epub 2019 Mar 8.

  PMID: 30857647 BACKGROUND

• Wesson DE, Mathur V, Tangri N, Stasiv Y, Parsell D, Li E, Klaerner G, Bushinsky DA. Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension. Lancet. 2019 Aug 3;394(10196):396-406. doi: 10.1016/S0140-6736(19)31388-1. Epub 2019 Jun 24.

  PMID: 31248662 BACKGROUND

• Bushinsky DA, Hostetter T, Klaerner G, Stasiv Y, Lockey C, McNulty S, Lee A, Parsell D, Mathur V, Li E, Buysse J, Alpern R. Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD. Clin J Am Soc Nephrol. 2018 Jan 6;13(1):26-35. doi: 10.2215/CJN.07300717. Epub 2017 Nov 4.

  PMID: 29102959 BACKGROUND

• Dawson-Hughes B, Harris SS, Palermo NJ, Castaneda-Sceppa C, Rasmussen HM, Dallal GE. Treatment with potassium bicarbonate lowers calcium excretion and bone resorption in older men and women. J Clin Endocrinol Metab. 2009 Jan;94(1):96-102. doi: 10.1210/jc.2008-1662. Epub 2008 Oct 21.

  PMID: 18940881 BACKGROUND

• Jehle S, Zanetti A, Muser J, Hulter HN, Krapf R. Partial neutralization of the acidogenic Western diet with potassium citrate increases bone mass in postmenopausal women with osteopenia. J Am Soc Nephrol. 2006 Nov;17(11):3213-22. doi: 10.1681/ASN.2006030233. Epub 2006 Oct 11.

  PMID: 17035614 BACKGROUND

• Jehle S, Hulter HN, Krapf R. Effect of potassium citrate on bone density, microarchitecture, and fracture risk in healthy older adults without osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab. 2013 Jan;98(1):207-17. doi: 10.1210/jc.2012-3099. Epub 2012 Nov 15.

  PMID: 23162100 BACKGROUND

• Moseley KF, Weaver CM, Appel L, Sebastian A, Sellmeyer DE. Potassium citrate supplementation results in sustained improvement in calcium balance in older men and women. J Bone Miner Res. 2013 Mar;28(3):497-504. doi: 10.1002/jbmr.1764.

  PMID: 22991267 BACKGROUND

• Krieger NS, Yao Z, Kyker-Snowman K, Kim MH, Boyce BF, Bushinsky DA. Increased bone density in mice lacking the proton receptor OGR1. Kidney Int. 2016 Mar;89(3):565-73. doi: 10.1016/j.kint.2015.12.020. Epub 2016 Jan 6.

  PMID: 26880453 BACKGROUND

• Dawson-Hughes B, Harris SS, Palermo NJ, Gilhooly CH, Shea MK, Fielding RA, Ceglia L. Potassium Bicarbonate Supplementation Lowers Bone Turnover and Calcium Excretion in Older Men and Women: A Randomized Dose-Finding Trial. J Bone Miner Res. 2015 Nov;30(11):2103-11. doi: 10.1002/jbmr.2554. Epub 2015 Jul 28.

  PMID: 25990255 BACKGROUND

MeSH Terms

Conditions

Bone Diseases, Metabolic

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Elise Danico, MS

CONTACT

617-636-3232; elise.danico@tuftsmedicine.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2026
• First Posted: March 16, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

US (1)