IOPForteo: Forteo for the Treatment of Unexplained Osteoporosis in Premenopausal Women

• Sponsor: Columbia University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00697463
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 22
• Locations: 2
• Arm: 1
• Actual Duration (Months): 40.4
• Patients Per Site: 11
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Idiopathic osteoporosis (IOP) is an uncommon disorder in which otherwise healthy young individuals sustain one or more low-trauma fractures. Teriparatide [PTH(1-34)], which is FDA approved for treatment of osteoporosis in men and postmenopausal women, works by stimulating bone formation. The investigators hypothesize that teriparatide will significantly increase bone density (BMD) and improve bone structure in premenopausal women with IOP.

Condition or Disease	Intervention/Treatment	Phase
Menopause; Fracture; Osteoporosis	Drug: Teriparatide (PTH 1-34)	Phase 2/Phase 3

Detailed Description

Idiopathic osteoporosis (IOP) is an uncommon disorder in which otherwise healthy young individuals sustain one or more low-trauma fractures. In studies of IOP in men, histomorphometric indices of bone formation are depressed, and affected men respond to PTH(1-34) with robust increases in lumbar spine (LS) bone mineral density (BMD). This is the beginning of the third year of an R01 (AR4989603) investigating the etiology and pathogenesis, as well as the histomorphometric and bone microarchitectural features of IOP in premenopausal women. There is evidence of markedly decreased bone formation and microarchitectural deterioration with decreased mechanical competence/strength.

Teriparatide [PTH(1-34)] is an anabolic agent that stimulates bone formation and improves bone microarchitecture. Based on findings, the investigators hypothesize that teriparatide will significantly increase BMD and improve microarchitecture in premenopausal women with IOP.

This is an open-label study of carefully characterized premenopausal women with IOP who are participating in a NIH-funded study and who have fragility fractures or very low bone density. Participants in the study will receive 18-24 months of teriparatide and the effects on BMD and microstructure, bone mechanical competence, and bone turnover will be assessed. In order to assess whether teriparatide stimulates bone formation to the same extent in women with IOP as it does in normal women, the study will compare the short-term changes (2 and 4 weeks) in biochemical markers of bone formation in response to teriparatide between women with IOP and normal women who are participating in another NIH-funded study as controls.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Teriparatide for the Treatment of Idiopathic Osteoporosis in Premenopausal Women
• Actual Study Start Date: Aug 20, 2008
• Actual Primary Completion Date: Jan 3, 2012
• Actual Study Completion Date: Jan 3, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Women with Idiopathic osteoporosis (IOP) Each subject will receive 20 micrograms of Teriparatide (PTH 1-34) subcutaneously daily for 18 -24 months	Drug: Teriparatide (PTH 1-34); 20 micrograms subcutaneous injection daily; Other Names: Forteo

Outcome Measures

Primary Outcome Measures

1. Change in Lumbar Spine Bone Density by Dual Energy X-ray Absorptiometry (DXA) [Baseline, Month 18 or 24 reported]

   Areal BMD at the lumbar spine was measured by dual energy x-ray absorptiometry (DXA) at baseline and at 6, 12, 18, and 24 months, if possible.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 48 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Premenopausal women of all races.

• Ages 20 to 48.

• Regular menses (at least 8 periods in the last 12 months).

• FSH < 20 mIU/ml during the early follicular phase, to exclude women in the perimenopause.

• Fracture subjects: documented low trauma fracture(s) at age >= 18 (e.g., fracture associated with a fall from a standing height or less).

• Low BMD subjects: DXA BMD T score less than or equal to 2.5 at the LS, total hip, femoral neck or distal radius, who have not had a fracture.

• Control subjects: DXA BMD T score greater than or equal to 1.0 at the LS, total hip, femoral neck and distal radius, who have not had a fracture.

• All subjects must use appropriate birth control methods to prevent pregnancy for the duration of teriparatide treatment.

Exclusion Criteria:

• Secondary Causes of Osteoporosis.

• Disorders of mineral metabolism: primary or secondary hyperparathyroidism (serum intact PTH > 65 pg/ml), vitamin D deficiency (serum 25OHD < 30 ng/ml), hypercalciuria (>300 mg/g creatinine), Paget's disease, clinical osteomalacia, osteogenesis imperfecta (OI).

• Recent pregnancy or lactation (within past year).

• Prolonged amenorrhea (> 6 months) during reproductive years (except during pregnancy or lactation).

• History of anorexia nervosa.

• Malignancy, except cured basal or squamous cell skin carcinoma.

• Endocrinopathy: hyperthyroidism (elevated serum thyroxine and/or suppressed TSH), untreated hypothyroidism, Cushing's syndrome, prolactin-secreting pituitary adenoma.

• Renal insufficiency (serum creatinine above upper limit of female normal range).

• Liver disease (AST, ALT, bilirubin, total alkaline phosphatase activity above upper normal limit).

• Intestinal disorders (celiac disease, pancreatic insufficiency, inflammatory bowel disease).

• History or current use of glucocorticoids, anticonvulsants, anticoagulants, diuretics, methotrexate.

• Current use of depot preparations of progesterone or GnRH agonists.

• Current use of drug therapies for osteoporosis (estrogen preparations other than contraceptives, raloxifene, bisphosphonates, calcitonin, PTH). Subjects who agree to discontinue use of these medications will be eligible to participate 6 months after discontinuing raloxifene or calcitonin, and 12 months after discontinuing bisphosphonates. Total exposure to bisphosphonates must be < 1 year. Subjects who have taken PTH at any time in the past will not be eligible.

• Additional contraindications to teriparatide use: Unexplained elevated total or bone specific alkaline phosphatase or prior external beam or implant radiation therapy involving the skeleton.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Creighton University	Omaha	Nebraska	United States	68131
2	Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• Columbia University
• Eli Lilly and Company

Investigators

• Principal Investigator: Elizabeth Shane, MD, Columbia University
• Study Director: Adi Cohen, MD, Columbia University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Elizabeth Shane, Professor of Medicine, Endocrinology, Columbia University
• ClinicalTrials.gov Identifier: NCT00697463
• Other Study ID Numbers: AAAC6871
• First Posted: Jun 13, 2008
• Last Update Posted: Jul 26, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Elizabeth Shane, Professor of Medicine, Endocrinology, Columbia University: Teriparatide; Forteo; Osteopenia; Osteoporosis; Fracture; Low Bone Density; Premenopausal women
• Additional relevant MeSH terms: Osteoporosis; Teriparatide

Study Results

Participant Flow

Recruitment Details	Premenopausal women, aged 20-48, with documented adult low trauma fractures or low aBMD by DXA; T score<-2.5 or Z score<-2.0 at the spine or hip and no history of adult low trauma fracture, were recruited at Columbia University Medical Center, NY and Creighton University, NE by advertisement, self- or physician referral.
Pre-assignment Detail	No pre-assignment details to report

Arm/Group Title	Women With Idiopathic Osteoporosis (IOP)
Arm/Group Description	Each subject will receive 20 micrograms of teriparatide subcutaneously daily. Teriparatide (PTH 1-34): 20 micrograms subcutaneous injection daily for 18- 24 months
Period Title: Overall Study
STARTED	22
COMPLETED	21
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Women With Idiopathic Osteoporosis (IOP)
Arm/Group Description	Each subject will receive 20 micrograms of teriparatide subcutaneously daily. Teriparatide (PTH 1-34): 20 micrograms subcutaneous injection daily for 18-24 months
Overall Participants	22
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	22 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.6 (5.4)
Sex: Female, Male (Count of Participants)
Female	22 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	22 100%

Outcome Measures

1. Primary Outcome

Title	Change in Lumbar Spine Bone Density by Dual Energy X-ray Absorptiometry (DXA)
Description	Areal BMD at the lumbar spine was measured by dual energy x-ray absorptiometry (DXA) at baseline and at 6, 12, 18, and 24 months, if possible.
Time Frame	Baseline, Month 18 or 24 reported

Outcome Measure Data

Analysis Population Description

Of 22 women with IOP who enrolled, one withdrew for personal reasons, therefore the overall number of participants analyzed is 21. The percentage of BMD change is calculated for each participant between baseline and Month 24 or between baseline and Month 18, whichever is the longer reported timeframe as some are lost to follow up by Month 24.

Arm/Group Title	Women With Idiopathic Osteoporosis (IOP)
Arm/Group Description	Each subject will receive 20 micrograms of teriparatide subcutaneously daily. Teriparatide (PTH 1-34): 20 micrograms subcutaneous injection daily for 18-24 months
Measure Participants	21
Mean (Standard Deviation) [percentage of BMD change]	10.8 (8.3)

Adverse Events

Time Frame	Adverse events were assessed through study completion.
Adverse Event Reporting Description	The definition of adverse event and/or serious adverse event used to collect adverse event information is the same.
Arm/Group Title	Women With Idiopathic Osteoporosis (IOP)
Arm/Group Description	Each subject will receive 20 micrograms of teriparatide subcutaneously daily. Teriparatide (PTH 1-34): 20 micrograms subcutaneous injection daily for 18-24 months
All Cause Mortality
	Women With Idiopathic Osteoporosis (IOP)
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Serious Adverse Events
	Women With Idiopathic Osteoporosis (IOP)
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Other (Not Including Serious) Adverse Events
	Women With Idiopathic Osteoporosis (IOP)
	Affected / at Risk (%)	# Events
Total	8/21 (38.1%)
Blood and lymphatic system disorders
Hypercalcemia	1/21 (4.8%)	1
Musculoskeletal and connective tissue disorders
Distal radius fracture	1/21 (4.8%)	1
Renal and urinary disorders
Hypercalciuria	6/21 (28.6%)	7

Limitations/Caveats

Without an untreated control group, we cannot attribute the observed effects to teriparatide with certainty. The effects of teriparatide on fractures could not be evaluated. Six women received teriparatide for 18 months rather than for 24 months.

More Information

Certain Agreements

All Principal Investigators ARE 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.