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PTH & Ibandronate Combination Study (PICS) (PICS)

Primary Purpose

Osteoporosis

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

PTH(1-84)

Ibandronate

Placebo injection

Placebo pills

About this trial

This is an interventional treatment trial for Osteoporosis focused on measuring Combination of PTH and ibandronate, Bone marker formation, Postmenopausal, Trabecular spine BMD

Eligibility Criteria

55 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Female
Aged 55-75 years, inclusive, at randomization
Postmenopausal for >= 5 years (no menses for at least 5 years)
Have an evaluable bone mineral density scan (DXA) at the spine AND at the hip with a T-score <= -1.5 either at the spine or the femoral neck or total hip OR have a T-score <= -1.0 with at least one of the following risk factors for fracture: 1)Age >= 65 years; 2)History of post-menopausal fracture (non-vertebral or vertebral); 3)Maternal history of hip fracture.
Be willing and able to self-administer daily injections
Signed written consent form.

Exclusion Criteria:

History of more than 12 months of oral bisphosphonate use ever, or any use (>4 weeks) with the past 12 months. For those with 4 weeks to 12 months of previous use, a 24 month washout is required.
History of any IV bisphosphonate use.
History of more than 12 month of PTH use ever, or any use (>4 weeks) with the past 12 months.
History of estrogen (oral or patch) more than one month in the last 6 months or for more than 12 months in the last 2 years.
Have type 1 or uncontrolled type 2 diabetes mellitus (defined as hemoglobin A1C > 10.0), or currently using insulin.
Have serum calcium >10.2 mg/dl.
Have Vitamin D level <15 nanograms/ml.
Have Stage III renal insufficiency where calculated creatinine clearance < 40 ml/min by MDRD.
Have any history of kidney stones in the last 10 years.
Have any history of hypercalcuria or currently have urine calcium >300 mg/24 hours.
Have any history of hypercalcemia.
Have any history of sarcoidosis.
Have any history of hyperparathyroidism.
Have any history of active or treated tuberculosis or other granulomatous disorders.
History of breast cancer, melanoma or hematologic malignancy which has required treatment within the last 10 years.
Any history of bone cancer or Paget's disease of bone
Any other metabolic bone disease which has required treatment within the last 10 years.
History of any other non-skin cancer which has required treatment within the last 10 years.
Have a documented history of symptomatic esophageal reflux, achalasia or esophageal stricture.
Be currently taking > 7.5 mg systemic prednisone or equivalent per day or for more than 10 days in the last 3 months.
Be currently using > 2 puffs, 4 times / day of inhaled steroids.
Be currently taking anticoagulants.
Be currently taking anticonvulsants that alter hepatic vitamin D clearance
Have used Calcitonin within the past 3 months.
Have used Raloxifene in the last 6 months or for more than 12 months in the last 2 years.
Have used Tamoxifen in the last 6 months or for more than 12 months in the last 2 years.
Have used fluoride for at least a month within the past 5 years.
Be currently taking > 1000 IU/day Vitamin D
Using Vitamin D analogues or metabolites.
Be currently taking thyroid hormone replacement AND have a TSH < 0.1mIU/L.
Have any major life-threatening illness.
Concurrent enrollment in another double-blinded clinical treatment intervention study.
Life expectancy less than 3 years
Willing to discontinue all over the counter nutritional supplements

Sites / Locations

University of California, San Francisco

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

A: 6 months both + 18 months oral only

B: (3 months injection + 9 months oral) x 2 years

Arm Description

Group A will receive 6 months of monthly oral ibandronate 150 mg, plus daily PTH 1-84, 1.4 mg; followed by 18 months of ibandronate only. Placebo injections will be given months 13-15. Calcium + Vitamin D supplements, plus multivitamins are provided.

Group B will receive 3 months of daily PTH 1-84, 1.4 mg; followed by 9 months of monthly oral ibandronate, 150 mg in year 1. In year 2, the group will receive another 3 months of daily PTH 1-84; followed by 9 months of monthly ibandronate. Placebo monthly pills will be given months 1-3 and months 13-15, and placebo injections will be given months 4-6. Calcium + Vitamin D supplements, plus multivitamins are provided.

Outcomes

Primary Outcome Measures

P1NP (ng/ml) Change From Baseline.

After an overnight fast, serum was drawn at baseline and 1, 3, 6, 12, 15, 18 and 24 months. Samples were stored at -70C until batch assayed in a central laboratory. Serum N-propeptide of type I collagen (P1NP) and C-terminal telopeptide of type I collagen (CTX) were measured by electrochemiluminescent immunoassay. Bone-specified alkaline phosphate (BAP) was measured by paramagnetic particle immunoassay. P1NP was the bone turnover marker upon which we based sample size calculations.

Secondary Outcome Measures

Change From Baseline in Trabecular Spine vBMD

Areal bone mineral density (aBMD) at the lumbar spine, hip, and distal one-third radius was assessed by dual-energy X-ray absorption at baseline and 6, 12, 18, and 24 months. The precision for aBMD is 1.0%. Volumetric BMD and bone geometry in trabecular and cortical compartments were assessed by quantitative computed tomography (QCT) at the spine and hip. The left hip was used for analysis. The precision for trabecular spine vBMD measurement is 1.0%. Trabecular spine vBMD was our primary BMD outcome, thus the one presented here.

Full Information

NCT ID

NCT00683163

First Posted

May 20, 2008

Last Updated

August 29, 2013

Sponsor

University of California, San Francisco

1. Study Identification

Unique Protocol Identification Number

NCT00683163

Brief Title

PTH & Ibandronate Combination Study (PICS)

Acronym

PICS

Official Title

PTH & Ibandronate Combination Study (PICS): Optimizing the Use of PTH With Boniva (Pilot Randomized Controlled Trial)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2013

Overall Recruitment Status

Completed

Study Start Date

May 2008 (undefined)

Primary Completion Date

April 2011 (Actual)

Study Completion Date

April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of California, San Francisco

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study will test in several innovative ways, several different combinations of PTH and oral monthly ibandronate for the treatment of osteoporosis in postmenopausal women. The intension is to provide other options for treatment than the current standard 2 year course of drug therapy. These options may lead to treatment where the two years of therapy are spread over several years.

Detailed Description

This randomized double-blind clinical trial for the treatment of postmenopausal osteoporosis will be conducted and coordinated by study investigators who also participated in the investigator-initiated PaTH study. Final data analysis will compare the results from this trial with those from the PaTH study. In the PaTH study, 238 women between 55 and 85 years of age were randomized to receive either: PTH for 1 year followed by alendronate for 1 year PTH and alendronate for 1 year followed by alendronate for 1 year alendronate for 2 years PTH for 1 year followed by placebo for 1 year. In the PICS 44 postmenopausal women between the ages of 55 to 75 years of age with osteoporosis who meet the inclusion/exclusion criteria,will be randomized to the following 2 treatment groups. Group A will received 6 months of monthly Ibandronate, plus daily PTH 1-84,100 μg; followed by 18 months of Ibandronate only. Group B will received 3 months of daily PTH 1-84,100 μg; followed by 9 months of monthly Ibandronate, over 2 years. Calcium (400-650 mg) and Vitamin D (400 IU) supplements will be provided to all participants. The primary objective is to determine if, at 3 months, the women treated with the concurrent combination of PTH and ibandronate (Group A) show a significant increase in bone marker formation compared to baseline (unlike the combination PTH/alendronate-treated women in PaTH). This will be accessed by examining the change in the markers P1NP, BSAP and serum CTX. As a secondary objective, we will compare the trabecular spine BMD measures of those treated with concurrent PTH/Ibandronate (Group A) to those who received 3 months of PTH followed by Ibandronate(Group B). Another secondary objective will be to compare changes between groups in trabecular bone and DXA spine BMD after 2 years of treatment. Changes to the fat content of the vertebrae during a course of PTH therapy will be examined using MRI spinal spectroscopy. Crosstabulation of these changes against changes in trabecular BMD, should indicate an effect on measurements. As well, the effect of a second three-month course of PTH therapy in Group B is of major interest.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Osteoporosis

Keywords

Combination of PTH and ibandronate, Bone marker formation, Postmenopausal, Trabecular spine BMD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

44 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A: 6 months both + 18 months oral only

Arm Type

Active Comparator

Arm Description

Arm Title

B: (3 months injection + 9 months oral) x 2 years

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

PTH(1-84)

Other Intervention Name(s)

In Europe, PTH(1-84) is marketed as Preotact.

Intervention Description

1.4 mg injected subcutaneously (in the abdomen) daily

Intervention Type

Drug

Intervention Name(s)

Ibandronate

Other Intervention Name(s)

Boniva

Intervention Description

150mg by mouth once monthly

Intervention Type

Other

Intervention Name(s)

Placebo injection

Intervention Description

Daily injections as placebo for PTS 1-84

Intervention Type

Other

Intervention Name(s)

Placebo pills

Intervention Description

Monthly pills as placebo for oral ibandronate

Primary Outcome Measure Information:

Title

P1NP (ng/ml) Change From Baseline.

Description

Time Frame

Baseline, 3 months

Secondary Outcome Measure Information:

Title

Change From Baseline in Trabecular Spine vBMD

Description

Time Frame

Baseline, 24 months.

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

55 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Female Aged 55-75 years, inclusive, at randomization Postmenopausal for >= 5 years (no menses for at least 5 years) Have an evaluable bone mineral density scan (DXA) at the spine AND at the hip with a T-score <= -1.5 either at the spine or the femoral neck or total hip OR have a T-score <= -1.0 with at least one of the following risk factors for fracture: 1)Age >= 65 years; 2)History of post-menopausal fracture (non-vertebral or vertebral); 3)Maternal history of hip fracture. Be willing and able to self-administer daily injections Signed written consent form. Exclusion Criteria: History of more than 12 months of oral bisphosphonate use ever, or any use (>4 weeks) with the past 12 months. For those with 4 weeks to 12 months of previous use, a 24 month washout is required. History of any IV bisphosphonate use. History of more than 12 month of PTH use ever, or any use (>4 weeks) with the past 12 months. History of estrogen (oral or patch) more than one month in the last 6 months or for more than 12 months in the last 2 years. Have type 1 or uncontrolled type 2 diabetes mellitus (defined as hemoglobin A1C > 10.0), or currently using insulin. Have serum calcium >10.2 mg/dl. Have Vitamin D level <15 nanograms/ml. Have Stage III renal insufficiency where calculated creatinine clearance < 40 ml/min by MDRD. Have any history of kidney stones in the last 10 years. Have any history of hypercalcuria or currently have urine calcium >300 mg/24 hours. Have any history of hypercalcemia. Have any history of sarcoidosis. Have any history of hyperparathyroidism. Have any history of active or treated tuberculosis or other granulomatous disorders. History of breast cancer, melanoma or hematologic malignancy which has required treatment within the last 10 years. Any history of bone cancer or Paget's disease of bone Any other metabolic bone disease which has required treatment within the last 10 years. History of any other non-skin cancer which has required treatment within the last 10 years. Have a documented history of symptomatic esophageal reflux, achalasia or esophageal stricture. Be currently taking > 7.5 mg systemic prednisone or equivalent per day or for more than 10 days in the last 3 months. Be currently using > 2 puffs, 4 times / day of inhaled steroids. Be currently taking anticoagulants. Be currently taking anticonvulsants that alter hepatic vitamin D clearance Have used Calcitonin within the past 3 months. Have used Raloxifene in the last 6 months or for more than 12 months in the last 2 years. Have used Tamoxifen in the last 6 months or for more than 12 months in the last 2 years. Have used fluoride for at least a month within the past 5 years. Be currently taking > 1000 IU/day Vitamin D Using Vitamin D analogues or metabolites. Be currently taking thyroid hormone replacement AND have a TSH < 0.1mIU/L. Have any major life-threatening illness. Concurrent enrollment in another double-blinded clinical treatment intervention study. Life expectancy less than 3 years Willing to discontinue all over the counter nutritional supplements

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dennis M. Black, PhD

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California, San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94115

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

21448966

Citation

Li X, Kuo D, Schafer AL, Porzig A, Link TM, Black D, Schwartz AV. Quantification of vertebral bone marrow fat content using 3 Tesla MR spectroscopy: reproducibility, vertebral variation, and applications in osteoporosis. J Magn Reson Imaging. 2011 Apr;33(4):974-9. doi: 10.1002/jmri.22489.

Results Reference

background

PubMed Identifier

23589163

Citation

Schafer AL, Burghardt AJ, Sellmeyer DE, Palermo L, Shoback DM, Majumdar S, Black DM. Postmenopausal women treated with combination parathyroid hormone (1-84) and ibandronate demonstrate different microstructural changes at the radius vs. tibia: the PTH and Ibandronate Combination Study (PICS). Osteoporos Int. 2013 Oct;24(10):2591-601. doi: 10.1007/s00198-013-2349-y. Epub 2013 Apr 16.

Results Reference

result

PubMed Identifier

22791766

Citation

Schafer AL, Sellmeyer DE, Palermo L, Hietpas J, Eastell R, Shoback DM, Black DM. Six months of parathyroid Hormone (1-84) administered concurrently versus sequentially with monthly ibandronate over two years: the PTH and ibandronate combination study (PICS) randomized trial. J Clin Endocrinol Metab. 2012 Oct;97(10):3522-9. doi: 10.1210/jc.2012-1844. Epub 2012 Jul 12.

Results Reference

result

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PTH & Ibandronate Combination Study (PICS)

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