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Teriparatide for Joint Erosions in Rheumatoid Arthritis: The TERA Trial (TERA)

This study has been completed.
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: February 28, 2017
Last verified: February 2017
  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 Drug: calcium citrate Drug: Vitamin D Drug: TNF antagonist Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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 Daniel H. Solomon, M.D.,MPH, Brigham and Women's Hospital:

Primary Outcome Measures:
  • Change From Baseline in Joint Erosion Volume Measured by 3-Dimensional Computed Tomography (3D CT) Scan [ Time Frame: Baseline and Month 12 ]
    Both hands were scanned using a CT scanner. A semi-automated software tool was used to segment the erosion margins in 3D. A board certified radiologist identified the individual erosions in six sub-regions: radius, ulna, proximal carpals, distal carpals, metacarpophalangeal (MCP) joints and proximal interphalangeal (PIP) joints. The average total in a single hand/wrist was calculated. A negative change from Baseline(less joint erosions) indicates improvement.


Secondary Outcome Measures:
  • Change From Baseline in Bone Mineral Density (BMD) Measured by Dual-Energy X-ray Absorptiometry (DXA) and Instant Vertebral Assessment (IVA) Scan [ Time Frame: Baseline and Month 12 ]
    BMD was measured at the lumbosacral spine antero-posterior and at the femoral neck using a densitometer. A positive change from Baseline (increased bone density) indicates improvement.

  • Change From Baseline in Disease Activity Score 28 Joint Count C-Reactive Protein (DAS-28 CRP) [ Time Frame: Baseline and Month 12 ]
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and C-Reactive Protein (CRP) for a total possible score of 2 to 10. Higher values indicate higher disease activity. A negative change from baseline indicates improvement.


Enrollment: 26
Study Start Date: August 2011
Study Completion Date: July 28, 2016
Primary Completion Date: July 30, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Teriparatide
The participants who are in treatment arm received teriparatide 20 μg, subcutaneous injection, 1 injection per day, with a biologic for 12 months. A second year of teriparatide was offered to all interested participants. All participants received daily 1000 milligrams (mg) of calcium citrate, 800 IU of vitamin D and a Tumor Necrosis Factor (TNF) antagonist.
Drug: Teriparatide
20 μg, subcutaneous injection, 1 injection per day
Other Name: Forteo
Drug: calcium citrate
1000 mg of calcium citrate
Drug: Vitamin D
800 IU of Vitamin D
Drug: TNF antagonist
TNF antagonist as prescribed in clinical practice (such as etanercept or adalimumab)
Control Arm
The participants randomized to the control arm had the same testing as those in the treatment arm and were offered teriparatide, if determined to be effective in healing bone erosions, after the first 12 months. All participants received daily 1000 mg of calcium citrate, 800 IU of vitamin D and a TNF antagonist.
Drug: calcium citrate
1000 mg of calcium citrate
Drug: Vitamin D
800 IU of Vitamin D
Drug: TNF antagonist
TNF antagonist as prescribed in clinical practice (such as etanercept or adalimumab)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   45 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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 posteroanterior (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 thyroid stimulating hormone (TSH). If PTH and/or 25-hydroxy vitamin D (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 calcium (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

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
University of Massachusetts Medical School
Worcester, Massachusetts, United States, 01605
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
Results First Received: February 28, 2017
Last Updated: February 28, 2017

Keywords provided by Daniel H. Solomon, M.D.,MPH, 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
Calcium, Dietary
Vitamin D
Ergocalciferols
Teriparatide
Vitamins
Citric Acid
Bone Density Conservation Agents
Physiological Effects of Drugs
Micronutrients
Growth Substances
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 26, 2017