PTH & Ibandronate Combination Study (PICS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00683163
First received: May 20, 2008
Last updated: August 29, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Osteoporosis
Drug: PTH(1-84)
Drug: Ibandronate
Other: Placebo injection
Other: Placebo pills
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: PTH & Ibandronate Combination Study (PICS): Optimizing the Use of PTH With Boniva (Pilot Randomized Controlled Trial)

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • P1NP (ng/ml) Change From Baseline. [ Time Frame: Baseline, 3 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 24 months. ] [ Designated as safety issue: No ]
    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.


Enrollment: 44
Study Start Date: May 2008
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A: 6 months both + 18 months oral only
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.
Drug: PTH(1-84)
1.4 mg injected subcutaneously (in the abdomen) daily
Other Name: In Europe, PTH(1-84) is marketed as Preotact.
Drug: Ibandronate
150mg by mouth once monthly
Other Name: Boniva
Other: Placebo injection
Daily injections as placebo for PTS 1-84
Active Comparator: B: (3 months injection + 9 months oral) x 2 years
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.
Drug: PTH(1-84)
1.4 mg injected subcutaneously (in the abdomen) daily
Other Name: In Europe, PTH(1-84) is marketed as Preotact.
Drug: Ibandronate
150mg by mouth once monthly
Other Name: Boniva
Other: Placebo injection
Daily injections as placebo for PTS 1-84
Other: Placebo pills
Monthly pills as placebo for oral ibandronate

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 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.

  Eligibility

Ages Eligible for Study:   55 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00683163

Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Dennis M. Black, PhD University of California, San Francisco
  More Information

Publications:
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00683163     History of Changes
Other Study ID Numbers: PICS001
Study First Received: May 20, 2008
Results First Received: April 1, 2013
Last Updated: August 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
Combination of PTH and ibandronate
Bone marker formation
Postmenopausal
Trabecular spine BMD

Additional relevant MeSH terms:
Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Ibandronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014