The Effects of Estrogen Replacement Therapy in Postmenopausal Women With Hypercalciuria and Low Bone Mass

• ClinicalTrials.gov Identifier: NCT01928082
• Recruitment Status: Terminated
• First Posted: August 23, 2013
• Results First Posted: March 7, 2018
• Last Update Posted: December 10, 2018
• Sponsor: University of Chicago
• Information provided by (Responsible Party): University of Chicago

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Hypercalciuria; Hypercalciuria, Familial Idiopathic; Osteopenia; Osteoporosis
• Intervention: Drug: Transdermal estradiol
• Enrollment: 1

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Transdermal Estradiol
Arm/Group Description	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Period Title: Overall Study
Started	1
Completed	0
Not Completed	1
Reason Not Completed
Study terminated.	1

Baseline Characteristics

Arm/Group Title		Transdermal Estradiol
Arm/Group Description		Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Baseline Participants		0
Baseline Analysis Population Description		data were not collected
Age, Continuous [1]	Number Analyzed	0 participants
		[1] Measure Analysis Population Description: Study terminated
Sex: Female, Male [1]
	Number Analyzed	0 participants
	Female
	Male
		[1] Measure Analysis Population Description: Study terminated.
Race and Ethnicity Not Collected [1]	Number Analyzed	0 participants
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.

Outcome Measures

1. Primary Outcome

Title	Absolute Change in 24 Hour Urinary Calcium Excretion
Description	0 participants were measured because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

0 participants were analyzed because the study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

2. Secondary Outcome

Title	Serum 1,25-dihydroxyvitamin D3
Description	0 participants were analyzed because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

The study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

3. Secondary Outcome

Title	Serum Bone Morphogenetic Protein 2
Description	Not available because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

the study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

4. Secondary Outcome

Title	Serum Sclerostin
Description	Not available because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

Not available because the study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

5. Other Pre-specified Outcome

Title	Serum Estradiol
Description	Not available because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

Not available because the study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

6. Other Pre-specified Outcome

Title	Serum Total Calcium
Description	Not available because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

Not available because the study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

7. Other Pre-specified Outcome

Title	Calculated Serum Ionized Calcium
Description	Not available because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

Not available because the study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

8. Other Pre-specified Outcome

Title	Calculated Tubular Resorption of Calcium
Description	Not available because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

Not available because the study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

9. Other Pre-specified Outcome

Title	Serum 25 Hydroxyvitamin D
Description	Not available because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

Not available because the study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

10. Other Pre-specified Outcome

Title	Serum Parathyroid Hormone
Description	Not available because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

Not available because the study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

11. Other Pre-specified Outcome

Title	Serum Phosphorus
Description	Not available because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

Not available because the study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

12. Other Pre-specified Outcome

Title	Serum Osteocalcin
Description	Not available because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

Not available because the study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

13. Other Pre-specified Outcome

Title	Serum Bone-specific Alkaline Phosphatase
Description	Not available because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

Not available because the study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

14. Other Pre-specified Outcome

Title	Serum C-telopeptides of Type 1 Collagen
Description	Not available because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

Not available because the study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

15. Other Pre-specified Outcome

Title	Serum Procollagen Type 1 N-terminal Propeptide
Description	It is not available because the study was terminated
Time Frame	4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

Not available because the study was terminated

Arm/Group Title	Transdermal Estradiol
Arm/Group Description:	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	The study was not finished and adverse events were not collected
Arm/Group Title	Transdermal Estradiol
Arm/Group Description	Transdermal estradiol 0.05 mg/day for 4 weeks, followed by 0.10 mg/day for 4 weeks Transdermal estradiol: 4 weeks of Vivelle-Dot 0.05 mg/day followed by 4 weeks of Vivelle-Dot 0.10 mg/day
All-Cause Mortality
	Transdermal Estradiol
	Affected / at Risk (%)
Total	0/0
Serious Adverse Events
	Transdermal Estradiol
	Affected / at Risk (%)
Total	0/0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Transdermal Estradiol
	Affected / at Risk (%)
Total	0/0

Limitations and Caveats

Early termination leading to 0 subjects analyzed

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Murray J. Favus
• Organization: The University of Chicago
• Phone: (773) 702-6138
• EMail: mfavus@medicine.bsd.uchicago.edu

Publications:

Cerda Gabaroi D, Peris P, Monegal A, Albaladejo C, Martinez MA, Muxi A, Martinez de Osaba MJ, Suris X, Guanabens N. Search for hidden secondary causes in postmenopausal women with osteoporosis. Menopause. 2010 Jan-Feb;17(1):135-9. doi: 10.1097/gme.0b013e3181ade8e5.

Christiansen C, Riis BJ, Rodbro P. Prediction of rapid bone loss in postmenopausal women. Lancet. 1987 May 16;1(8542):1105-8. doi: 10.1016/s0140-6736(87)91671-0.

Deutschmann HA, Weger M, Weger W, Kotanko P, Deutschmann MJ, Skrabal F. Search for occult secondary osteoporosis: impact of identified possible risk factors on bone mineral density. J Intern Med. 2002 Nov;252(5):389-97. doi: 10.1046/j.1365-2796.2002.01040.x.

Favus MJ, Karnauskas AJ, Parks JH, Coe FL. Peripheral blood monocyte vitamin D receptor levels are elevated in patients with idiopathic hypercalciuria. J Clin Endocrinol Metab. 2004 Oct;89(10):4937-43. doi: 10.1210/jc.2004-0412.

Frumar AM, Meldrum DR, Geola F, Shamonki IM, Tataryn IV, Deftos LJ, Judd HL. Relationship of fasting urinary calcium to circulating estrogen and body weight in postmenopausal women. J Clin Endocrinol Metab. 1980 Jan;50(1):70-5. doi: 10.1210/jcem-50-1-70.

Giannini S, Nobile M, Dalle Carbonare L, Lodetti MG, Sella S, Vittadello G, Minicuci N, Crepaldi G. Hypercalciuria is a common and important finding in postmenopausal women with osteoporosis. Eur J Endocrinol. 2003 Sep;149(3):209-13. doi: 10.1530/eje.0.1490209.

Lobo RA, Roy S, Shoupe D, Endres DB, Adams JS, Rude RK, Singer FR. Estrogen and progestin effects on urinary calcium and calciotropic hormones in surgically-induced postmenopausal women. Horm Metab Res. 1985 Jul;17(7):370-3. doi: 10.1055/s-2007-1013545.

McKane WR, Khosla S, Burritt MF, Kao PC, Wilson DM, Ory SJ, Riggs BL. Mechanism of renal calcium conservation with estrogen replacement therapy in women in early postmenopause--a clinical research center study. J Clin Endocrinol Metab. 1995 Dec;80(12):3458-64. doi: 10.1210/jcem.80.12.8530583.

Nordin BE, Horowitz M, Need A, Morris HA. Renal leak of calcium in post-menopausal osteoporosis. Clin Endocrinol (Oxf). 1994 Jul;41(1):41-5. doi: 10.1111/j.1365-2265.1994.tb03782.x.

Nordin BE, WIshart JM, Clifton PM, McArthur R, Scopacasa F, Need AG, Morris HA, O'Loughlin PD, Horowitz M. A longitudinal study of bone-related biochemical changes at the menopause. Clin Endocrinol (Oxf). 2004 Jul;61(1):123-30. doi: 10.1111/j.1365-2265.2004.02066.x.

Nordin BE, Need AG, Morris HA, Horowitz M. Biochemical variables in pre- and postmenopausal women: reconciling the calcium and estrogen hypotheses. Osteoporos Int. 1999;9(4):351-7. doi: 10.1007/s001980050158.

Nordin BE, Need AG, Morris HA, Horowitz M, Robertson WG. Evidence for a renal calcium leak in postmenopausal women. J Clin Endocrinol Metab. 1991 Feb;72(2):401-7. doi: 10.1210/jcem-72-2-401.

Puche RC, Roveri E, Perez Jimeno N, Roberti A, Poudes G, Bocanera R, Tozzini R. Hypercalciuria and urinary saturation measurements in climacteric women. Maturitas. 1993 Jan;16(1):39-47. doi: 10.1016/0378-5122(93)90132-2.

Stock JL, Coderre JA, Mallette LE. Effects of a short course of estrogen on mineral metabolism in postmenopausal women. J Clin Endocrinol Metab. 1985 Oct;61(4):595-600. doi: 10.1210/jcem-61-4-595.

Voetberg GA, Netelenbos JC, Kenemans P, Peters-Muller ER, van de Weijer PH. Estrogen replacement therapy continuously combined with four different dosages of dydrogesterone: effect on calcium and lipid metabolism. J Clin Endocrinol Metab. 1994 Nov;79(5):1465-9. doi: 10.1210/jcem.79.5.7962344.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT01928082
• Other Study ID Numbers: 12-0062
• First Submitted: August 20, 2013
• First Posted: August 23, 2013
• Results First Submitted: October 12, 2017
• Results First Posted: March 7, 2018
• Last Update Posted: December 10, 2018