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

Официальное название

Veverimer to Decrease Net Acid Excretion and Bone Resorption in Adults With Osteopenia: a Dose-finding Randomized Controlled Trial

Обзор

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

Вмешательства

• Препарат veverimer daily
  8 weeks of taking 9 grams of veverimer (a powder mixed into water) daily
• Препарат veverimer every other day
  8 weeks of taking 9 grams of veverimer (a powder mixed into water) every other day
• Другое Placebo
  8 weeks taking 9 grams microcrystalline cellulose (powdered mixed into water) daily or every other day

Первичные конечные точки

• 24-hr urinary net acid excretion [Срок оценки: measured at screening, week 2, week 8 and week 8 +1day]

Вторичные конечные точки (4)

• Serum bicarbonate level [Срок оценки: measured at screening, week 0, week 1, week 2, week 4, week 8]
• Serum potassium level [Срок оценки: measured at screening, week 0, week 1, week 2, week 4, week 8]
• Serum C-telopeptide level [Срок оценки: measured at week 0, week 2, week 8]
• Serum procollagen type 1 N-propeptide level [Срок оценки: measured at week 0 and week 8]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.
• Individuals who are unable to provide informed consent due to cognitive impairment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

США · 1 центр

• Tufts Medical Center — Boston

Публикации

• 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
• 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
• 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
• 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
• 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
• 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 PMID 21184054
• 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
• 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

Идентификаторы

NCT: NCT07473713 · STUDY00006557 · 1R61AR085647-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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