Clinical trial NCT00926380: Denosumab, Teriparatide or Both for the Treatment of Postmenopausal Osteoporosis
Official title: The Denosumab And Teriparatide Administration Study (DATA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoporosis
Keywords: osteoporosis
postmenopausal
denosumab
teriparatide
Forteo®
DXA
Bone Mineral Density
pQCT
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2009-06-23
Enrollment: 94
Sex: FEMALE
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to determine whether denosumab (an FDA-approved osteoporosis therapy), in combination with teriparatide (an FDA-approved osteoporosis therapy), will increase bone mineral density more than either one alone in postmenopausal osteoporotic women.


Eligibility criteria: Inclusion Criteria:

Must satisfy A and B and C and D below:

* (A) Women aged \> 55
* (B) Postmenopausal
* (C) Osteoporotic with high risk of fracture

Exclusion Criteria:

* Confirmed serum alkaline phosphatase above upper normal limit with no explanation
* Liver disease (AST or ALT \> 2 x upper normal limit).
* Renal disease (serum creatinine \> 2.0 mg/dl).
* Hypercalcemia (Ca \>10.5 mg/dL)
* Elevated blood PTH (intact PTH \> 65 pg/ml)
* Serum 25-OH vitamin D \< 20 ng/ml
* HCT \< 32%.
* History of malignancy (except basal cell carcinoma) or radiation therapy.
* Significant cardiopulmonary disease including unstable coronary artery disease, stage D ACC/AHA heart failure or any other condition that the investigator deems may preclude the subject from participating safely or completing the protocol procedures.
* Major psychiatric disease that in the opinion of the investigator would preclude the subject from providing adequate informed consent or completing the protocol procedures.
* Excessive alcohol use or substance abuse that in the opinion of the investigator would preclude the subject from providing adequate informed consent or completing the protocol procedures.
* Known congenital or acquired bone disease other than osteoporosis (including osteomalacia, hyperparathyroidism, Paget's disease)
* Current use or use in the past 6 months of oral bisphosphonate
* Current use or use within the past 3 months of estrogens, selective estrogen receptor modulators, or calcitonin.
* Use of oral or parenteral glucocorticoids for more than 14 days within the past 6 months.
* Any current or previous use of strontium or any parenteral bisphosphonate.
* Known sensitivity to mammalian cell-derived drug products.
* Known sensitivity to teriparatide or any of its excipients.

Primary outcomes:
measure: Change in Spine Bone Density From Baseline to 2 Years
timeFrame: Baseline and 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Benjamin Z Leder, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Robert M Neer, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ; PaTH Study Investigators. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med. 2003 Sep 25;349(13):1207-15. doi: 10.1056/NEJMoa031975. Epub 2003 Sep 20.
citation: Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med. 2003 Sep 25;349(13):1216-26. doi: 10.1056/NEJMoa035725. Epub 2003 Sep 20.
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citation: Kostenuik PJ, Capparelli C, Morony S, Adamu S, Shimamoto G, Shen V, Lacey DL, Dunstan CR. OPG and PTH-(1-34) have additive effects on bone density and mechanical strength in osteopenic ovariectomized rats. Endocrinology. 2001 Oct;142(10):4295-304. doi: 10.1210/endo.142.10.8437.
citation: Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998 Apr 17;93(2):165-76. doi: 10.1016/s0092-8674(00)81569-x.
citation: Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3597-602. doi: 10.1073/pnas.95.7.3597.
citation: Bone HG, Bolognese MA, Yuen CK, Kendler DL, Wang H, Liu Y, San Martin J. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab. 2008 Jun;93(6):2149-57. doi: 10.1210/jc.2007-2814. Epub 2008 Apr 1.
citation: Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone. 2008 Aug;43(2):222-229. doi: 10.1016/j.bone.2008.04.007. Epub 2008 Apr 26.
citation: Antoniucci DM, Sellmeyer DE, Bilezikian JP, Palermo L, Ensrud KE, Greenspan SL, Black DM. Elevations in serum and urinary calcium with parathyroid hormone (1-84) with and without alendronate for osteoporosis. J Clin Endocrinol Metab. 2007 Mar;92(3):942-7. doi: 10.1210/jc.2006-1788. Epub 2006 Dec 12.
citation: Tsai JN, Uihlein AV, Burnett-Bowie SM, Neer RM, Derrico NP, Lee H, Bouxsein ML, Leder BZ. Effects of Two Years of Teriparatide, Denosumab, or Both on Bone Microarchitecture and Strength (DATA-HRpQCT study). J Clin Endocrinol Metab. 2016 May;101(5):2023-30. doi: 10.1210/jc.2016-1160. Epub 2016 Mar 10.
citation: Leder BZ, Tsai JN, Uihlein AV, Wallace PM, Lee H, Neer RM, Burnett-Bowie SA. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet. 2015 Sep 19;386(9999):1147-55. doi: 10.1016/S0140-6736(15)61120-5. Epub 2015 Jul 2.
citation: Yu EW, Kumbhani R, Siwila-Sackman E, DeLelys M, Preffer FI, Leder BZ, Wu JY. Teriparatide (PTH 1-34) treatment increases peripheral hematopoietic stem cells in postmenopausal women. J Bone Miner Res. 2014 Jun;29(6):1380-6. doi: 10.1002/jbmr.2171.
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