Parathyroid Hormone (PTH) for Osteoporosis in Postmenopausal Women

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00086619
• Collaborator: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (NIH)
• Enrollment: 80
• Location: 1
• Arms: 2
• Duration (Months): 67
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Parathyroid hormone (PTH) increases bone formation and thereby improves bone density and bone strength in postmenopausal women with osteoporosis. However, prolonged PTH treatment increases bone formation less and less over time. This study will test whether increasing the daily dose of PTH sustains its ability to improve bone formation, and optional sub-studies will test several potential reasons why PTH's effects on bone formation decline over time.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Osteoporosis; Osteoporosis	Drug: synthetic hPTH 1-34	Phase 2

Detailed Description

In women with postmenopausal osteoporosis, PTH increases bone mineral density more than anti-resorptive agents, and its use markedly reduces the incidence of new spine and non-spine fractures. Still, PTH is not a cure for osteoporosis in many patients because PTH-stimulated bone formation declines as PTH therapy continues. Biochemical analyses suggest that bone formation and resorption peak after 6 to 9 months of daily PTH therapy and then decline progressively.

The study will last 18 months. Blood, urine, and bone density tests will occur at screening. At the start of the study, participants will be randomly assigned to one of two PTH dose regimens. Patients will go to Massachusetts General Hospital at Months 0, 3, 6, 9, 12, 15, and 18 for blood and urine collection. In addition, bone density tests by DXA will be performed at Months 0, 6, 12, and 18, and by quantitative CT scans at Months 0 and 18. Approximately 6 weeks after any change in PTH dose, each participant's blood calcium will be checked 4 to 6 hours after that day's PTH injection, and her 24-hour urine calcium excretion will also be checked.

Participants may enroll in optional substudies that will test whether reduced skeletal responses to long-term treatment with PTH are accompanied by changes in its absorption and/or destruction and whether reduced skeletal responses to long-term treatment with PTH are accompanied by parallel reductions in kidney responses to PTH.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Factors That Affect Skeletal Responses to PTH
• Study Start Date: May 1, 2004
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: constant dose Participants will receive synthetic human parathyroid hormone fragment 1-34 (hPTH 1-34) once-daily in a constant dose of 30 mcg/day.	Drug: synthetic hPTH 1-34; Either daily treatment with self-injected hPTH 1-34 or ascending dose treatment at 6-month intervals of hPTH 1-34; Other Names: synthetic human parathyroid hormone 1-34
Experimental: ascending dose Participants will receive synthetic human parathyroid hormone fragment 1-34 (hPTH 1-34) once-daily in a dose that ascends at 6 month intervals (20-30-40 mcg/day).	Drug: synthetic hPTH 1-34; Either daily treatment with self-injected hPTH 1-34 or ascending dose treatment at 6-month intervals of hPTH 1-34; Other Names: synthetic human parathyroid hormone 1-34

Outcome Measures

Primary Outcome Measures

1. Changes in Indices of Bone Turnover [Each index of bone turnover was measured at study month 0, 1.5, 3, 6, 7.5, 9, 12, 13.5, 15, and 18.]

   Change from month 0 (pre-treatment) baseline serum aminoterminal propeptide of type I collagen (PINP), osteocalcin (OC), and C-terminal telopeptide (CTX), expressed as an area under the curve (AUC). Each marker measurement result was multiplied by the corresponding subject-specific elapsed study time interval using the trapezoidal rule, and these products were summed to generate a subject-specific AUC (months*ng/ml) for the marker.

Secondary Outcome Measures

1. Change in Bone Mineral Density (BMD) [baseline and 18 months (12 months in 4 subjects)]

   Percent change in BMD of the spine, femur, radius, and ulna, and subtotal body, calculated as 100*[(final - month 0)/month 0] in subjects who took study therapy for at least 12 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 46 Years to 85 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Three or more years after menopause

• Bone mineral density T-score < or = -2.0 by dual-energy x-ray absorptiometry (DXA) of vertebrae or femoral neck, or by quantitative computerized tomography (QCT) of vertebral body trabeculae

Exclusion Criteria:

• Cannot walk without assistance

• Significant heart, kidney, liver, or malignant disease

• Current alcohol abuse

• Major psychiatric disorders

• Other current or past disorders known to affect bone

• Use of medications known to affect bone for > 7 days in the past 12 months

• Use of bisphosphonates or fluoride

• Abnormal blood calcium, PTH, 25-hydroxy vitamin D, creatinine, liver function tests, or complete blood count

• Elevated calcium levels in 24-hour urine collection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

• Principal Investigator: Robert M. Neer, MD, Massachusetts General Hospital
• Principal Investigator: Joel S. Finkelstein, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert M. Neer, MD, Associate Professor of Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00086619
• Other Study ID Numbers: NIAMS-123; 1P50AR044855
• First Posted: Jul 8, 2004
• Last Update Posted: Oct 30, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by Robert M. Neer, MD, Associate Professor of Medicine, Massachusetts General Hospital: Osteoporosis; Parathyroid hormone; Teriparatide; Bone formation; Bone resorption
• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Parathyroid Hormone

Study Results

Participant Flow

Recruitment Details	Postmenopausal women with low bone density were recruited from 2004-2007 to participate in this study at a single academic medical center. Recruitment letters were sent to women in the Greater Boston area and the trial was also posted on clinicaltrials.gov.
Pre-assignment Detail	Must satisfy inclusion and exclusion criteria.

Arm/Group Title	Constant Dose PTH	Ascending Dose PTH
Arm/Group Description	Participants received constant dose synthetic hPTH 1-34 (30 mcg/day).	Participants received ascending dose synthetic hPTH 1-34 (20-30-40 mcg/day).
Period Title: Overall Study
STARTED	40	40
Completed Baseline Visit	34	36
Completed 12 Month Visit	26	26
COMPLETED	25	23
NOT COMPLETED	15	17

Baseline Characteristics

Arm/Group Title	Constant Dose PTH	Ascending Dose PTH	Total
Arm/Group Description	Participants received constant dose synthetic hPTH 1-34 (30 mcg/day).	Participants received ascending dose synthetic hPTH 1-34 (20-30-40 mcg/day).	Total of all reporting groups
Overall Participants	40	40	80
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	26 65%	27 67.5%	53 66.3%
>=65 years	14 35%	13 32.5%	27 33.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.3 (7.6)	62.1 (8.9)	62.7 (8.2)
Sex: Female, Male (Count of Participants)
Female	40 100%	40 100%	80 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	40 100%	40 100%	80 100%

Outcome Measures

1. Primary Outcome

Title	Changes in Indices of Bone Turnover
Description	Change from month 0 (pre-treatment) baseline serum aminoterminal propeptide of type I collagen (PINP), osteocalcin (OC), and C-terminal telopeptide (CTX), expressed as an area under the curve (AUC). Each marker measurement result was multiplied by the corresponding subject-specific elapsed study time interval using the trapezoidal rule, and these products were summed to generate a subject-specific AUC (months*ng/ml) for the marker.
Time Frame	Each index of bone turnover was measured at study month 0, 1.5, 3, 6, 7.5, 9, 12, 13.5, 15, and 18.

Outcome Measure Data

Analysis Population Description

Because this was a physiologic study evaluating the impact of stepwise increases in teriparatide, per protocol analysis was performed as was pre-specified in our analysis plan. Outcomes data were analyzed in women who remained on teriparatide throughout the first stepwise increase (i.e. until month 12 or later).

Arm/Group Title	Constant Dose PTH	Ascending Dose PTH
Arm/Group Description	Participants received constant dose synthetic hPTH 1-34 (30 mcg/day).	Participants received ascending dose synthetic hPTH 1-34 (20-30-40 mcg/day).
Measure Participants	26	26
PINP	4418 (2732)	3696 (1735)
OC	956 (416)	822 (312)
CTX	22 (11)	19 (9)

2. Secondary Outcome

Title	Change in Bone Mineral Density (BMD)
Description	Percent change in BMD of the spine, femur, radius, and ulna, and subtotal body, calculated as 100*[(final - month 0)/month 0] in subjects who took study therapy for at least 12 months.
Time Frame	baseline and 18 months (12 months in 4 subjects)

Outcome Measure Data

Analysis Population Description

Final BMD was measured after 18 months of study therapy in 48 subjects and measured after 12 months of study therapy in 4 others who thereafter dropped out prematurely. Of the latter 4, 3 were in the ascending dose arm and 1 was in the constant dose arm.

Arm/Group Title	Constant Dose PTH	Ascending Dose PTH
Arm/Group Description	Participants received constant dose synthetic hPTH 1-34 (30 mcg/day).	Participants received ascending dose synthetic hPTH 1-34 (20-30-40 mcg/day).
Measure Participants	26	26
1/3 Radius BMD	-4.6 (2.8)	-3.1 (3.3)
Femoral neck BMD	1.7 (3.0)	3.5 (2.7)
Spine BMD	5.9 (4.6)	7.4 (3.8)
Subtotal BMD	-1.6 (0.8)	-0.9 (0.5)
Total hip BMD	1.4 (3.1)	1.3 (2.5)

Adverse Events

Arm/Group Title	Constant Dose PTH		Ascending Dose PTH
Arm/Group Description	Participants received constant dose synthetic hPTH 1-34 (30 mcg/day).		Participants received ascending dose synthetic hPTH 1-34 (20-30-40 mcg/day).
All Cause Mortality
	Constant Dose PTH		Ascending Dose PTH
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Constant Dose PTH		Ascending Dose PTH
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		2/40 (5%)
Endocrine disorders
Hypercalcemia requiring emergency room visit	0/40 (0%)	0	1/40 (2.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diagnosed with lung cancer	0/40 (0%)	0	1/40 (2.5%)	1
Other (Not Including Serious) Adverse Events
	Constant Dose PTH		Ascending Dose PTH
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/40 (12.5%)		8/40 (20%)
Blood and lymphatic system disorders
Lower extremity edema	1/40 (2.5%)	1	0/40 (0%)	0
Endocrine disorders
Mild hypercalcemia or hypercalciuria	3/40 (7.5%)	3	5/40 (12.5%)	5
Gastrointestinal disorders
Nausea	1/40 (2.5%)	1	1/40 (2.5%)	1
Musculoskeletal and connective tissue disorders
Joint pain	0/40 (0%)	0	1/40 (2.5%)	1
Back pain	0/40 (0%)	0	1/40 (2.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.