Teriparatide for Joint Erosions in Rheumatoid Arthritis: The TERA Trial

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Brigham and Women's Hospital
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Daniel H. Solomon, M.D.,MPH, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01400516
First received: July 21, 2011
Last updated: June 24, 2014
Last verified: June 2014
  Purpose

Summary:

The investigators propose a randomized controlled open label study of teriparatide in men or women with rheumatoid arthritis and joint erosions. Specifically, the investigators will examine whether teriparatide in combination with a biologic can retard the development of joint erosions. The study will be conducted at Brigham and Women's Hospital Arthritis Center, several Brigham and Women's Hospital Arthritis Center satellite practices, the University of Massachusetts Medical Center, and Massachusetts General Hospital.

Hypothesis:

The investigators hypothesize that the combination of teriparatide with biologic will be much more effective at retarding erosion progression then a biologic alone.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Teriparatide
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Teriparatide for Joint Erosions in Rheumatoid Arthritis: The TERA Trial

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • Joint Erosion by 3D CT scan [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Joint erosion scores, measured by 3D CT scan, will be significantly improved at study completion in patients taking teriparatide


Secondary Outcome Measures:
  • Lumbar by DXA [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Teriparatide will significantly increase BMD at all sites as measured by DXA.


Estimated Enrollment: 50
Study Start Date: August 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm
The subjects who are in treatment arm will receive teriparatide with a biologic. A second year of teriparatide will be offered to all interested subjects.
Drug: Teriparatide
20 mcg, subcutaneous injection, 1 injection per day
Other Name: Forteo
No Intervention: Control Arm
The subjects randomized to the control arm will undergo the same testing as those in the treatment arm and will be offered teriparatide, if determined to be effective in healing bone erosions, after the first 12 months.

Detailed Description:

I. Introduction:

While generalized osteoporosis causes tremendous disability in patients with RA and occurs relatively frequently in such patients, there has been little research on treatments for osteoporosis in patients with RA. Not only are there important questions about the effects of teriparatide on BMD in patients with RA, but little is known about how it might affect localized bone erosions or RA disease activity.

Recent data in a mouse model of RA suggest that intermittent PTH in the setting of potent immunosuppressives may indeed heal bone erosions. This study showed an additive effect of PTH in addition to a biologic on erosion healing. To the best of our knowledge, this has yet to be demonstrated in humans. That is the primary aim of the proposed study.

II. Objectives and Hypotheses:

To assess the effects of teriparatide among a group of patients with RA and erosions, all using biologics, with respect to:

  1. Joint erosion volume by 3D CT scan;
  2. Lumbar BMD by DXA;
  3. Hip BMD by DXA; and
  4. RA disease activity measured by the Disease Activity Score (DAS) and acute phase reactants.

The hypotheses to be tested include:

  1. Joint erosion scores, measured by 3D CT scan, will be significantly improved at study completion in patients taking teriparatide.
  2. Teriparatide will significantly increase BMD at all sites as measured by DXA.
  3. RA disease activity measures will be stable during the study year.
  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All men and women 45 years of age or older with RA and joint erosions by plain x-ray who are taking a biologic for at least three months and who have not taken more than two weeks of a bone active agent in the last 12 months will be eligible and screened for their interest in participating in the proposed randomized trial.

  1. RA will be defined according to the 2010 American College of Rheumatology/European League Against Rheumatism diagnostic and classification criteria.
  2. Osteopenic bone mineral density will be defined as a t-score between -1.0 and -2.5 on either a DXA of the PA or lateral lumbar spine or the femoral neck or total hip. Potential subjects with prior minimal trauma fractures will be excluded.

    2.Subjects must be able to give written informed consent.

Exclusion Criteria:

  1. A switch in DMARD in the last 3 months;
  2. Current use of chronic oral glucocorticoids > 5 milligrams per day;
  3. A prior history of intolerance to teriparatide;
  4. T-score < -2.5 or a prior minimal trauma fracture;
  5. Use of a bone active agent for over 2 weeks in the last 12 months (these agents include oral and intravenous bisphosphonates, hormone replacement therapy, calcitonin, raloxifene, teriparatide, suppressive doses of thyroxine, lithium, pharmacological doses of vitamin D (greater than 2000 IU/day or anticonvulsants);
  6. History of significant cardiac, hepatic, current alcohol abuse, or major psychiatric disorders;
  7. Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including hematologic malignancies and solid tumors, except basal cell carcinoma of the skin that has been excised and cured), or breast cancer diagnosed within the previous 20 years;
  8. No current diagnoses of disorders known to affect bone metabolism including hyperthyroidism, hyperparathyroidism, osteomalacia, or Paget's disease. All participants will be required to have normal serum levels of 25-OH vitamin D (> 20 ng/ml), intact PTH, and TSH. If PTH and/or 25-OH D levels are abnormal, subjects may be given calcium and/or multivitamin supplements and be re-tested in 2-12 weeks;
  9. Serum Ca > 10.6 mg/dl,and 24-hour urine calcium > 400 mg. If minor abnormalities are detected in any of these parameters, the test may be repeated;
  10. Patients who have had external beam radiation; and
  11. Patients currently on digoxin.
  12. Women that are currently pregnant or breast-feeding or plan on becoming pregnant over the course of participation in the study
  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: NCT01400516

Contacts
Contact: Daniel H Solomon, MD, MPH 617-732-5356 dhsolomon@partners.org
Contact: Emily Lo, MPH 617-732-8169 ylo3@partners.org

Locations
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Daniel H Solomon, MD, MPH    617-732-5356      
Contact: Emily Lo, MPH    617-732-8169      
Principal Investigator: Daniel H. Solomon, MD,MPH         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Marcy B. Bolster, M.D.    617-726-7938      
Contact: Emily Lo    617-732-8169      
Sub-Investigator: Marcy B. Bolster, M.D.         
University of Massachusetts Medical School Recruiting
Worcester, Massachusetts, United States, 01605
Contact: Ellen M. Gravallese, MD    508-856-8730      
Contact: Jonathan Kay, MD    508-334-6273      
Sub-Investigator: Ellen M. Gravallese, MD         
Sub-Investigator: Jonathan Kay, MD         
Sponsors and Collaborators
Brigham and Women's Hospital
Eli Lilly and Company
Investigators
Principal Investigator: Daniel H Solomon, MD, MPH Brigham and Women's Hospital
Principal Investigator: Ellen M. Gravallese, MD University of Massachusetts, Worcester
Principal Investigator: Jonathan Kay, MD University of Massachusetts, Worcester
Principal Investigator: Marcy B. Bolster, M.D. Massachusetts General Hospital
  More Information

Additional Information:
Publications:

Responsible Party: Daniel H. Solomon, M.D.,MPH, Principal Investigator, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01400516     History of Changes
Other Study ID Numbers: 2010P002691
Study First Received: July 21, 2011
Last Updated: June 24, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:
Rheumatoid Arthritis
Bone erosion
Osteopenia

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Teriparatide
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014