PTH & Ibandronate Combination Study (PICS)

Condition(s) targeted: Osteoporosis

Intervention: PTH 1-84 (Drug); Ibandronate (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: University of California, San Francisco

Official(s) and/or principal investigator(s):
Dennis M. Black, PhD, Principal Investigator, Affiliation: University of California, San Francisco

Overall contact:
Trisha Hue, MPH, PhD (cand.), Phone: 415-514-8000, Email: thue@psg.ucsf.edu

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.

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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study

Primary outcome: Bone marker formation

Secondary outcome: Trabecular spine BMD

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:

1. PTH for 1 year followed by alendronate for 1 year

2. PTH and alendronate for 1 year followed by alendronate for 1 year

3. alendronate for 2 years

4. PTH for 1 year followed by placebo for 1 year.

In the PICS 40 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.

Minimum age: 55 Years. Maximum age: 75 Years. Gender(s): Female.

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 mg/min

by MDRD.

- Have any history of kidney stones in the last 10 years.

- Have any history of hypercalcuria or currently have urine calcium/creatinine >300 mg.

- 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 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.

Trisha Hue, MPH, PhD (cand.), Phone: 415-514-8000, Email: thue@psg.ucsf.edu

University of California, San Francisco, San Francisco, California 94115, United States; Recruiting
Leyla Herrera, Phone: 415-353-9720

Related publications:

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. Epub 2003 Sep 20.

Black DM, Bilezikian JP, Ensrud KE, Greenspan SL, Palermo L, Hue T, Lang TF, McGowan JA, Rosen CJ; PaTH Study Investigators. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N Engl J Med. 2005 Aug 11;353(6):555-65.

Bauer DC, Garnero P, Bilezikian JP, Greenspan SL, Ensrud KE, Rosen CJ, Palermo L, Black DM. Short-term Changes in Bone Turnover Markers and Bone Mineral Density Response to Parathyroid Hormone in Postmenopausal Women with Osteoporosis. J Clin Endocrinol Metab. 2006 Jan 31; [Epub ahead of print]

Sellmeyer DE, Black DM, Palermo L, Greenspan S, Ensrud K, Bilezikian J, Rosen CJ. Hetereogeneity in skeletal response to full-length parathyroid hormone in the treatment of osteoporosis. Osteoporos Int. 2007 Feb 28; [Epub ahead of print]

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. Epub 2006 Dec 12.

Starting date: May 2008
Ending date: December 2010
Last updated: May 22, 2008