Teriparatide for Joint Erosions in Rheumatoid Arthritis: The TERA Trial
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Brigham and Women's Hospital
- Enrollment
- 26
- Locations
- 3
- Primary Endpoint
- Change From Baseline in Joint Erosion Volume Measured by 3-Dimensional Computed Tomography (3D CT) Scan
Study Overview
Brief Summary
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.
Detailed Description
I. Introduction:
While generalized osteoporosis causes tremendous disability in patients with Rheumatoid Arthritis (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 Bone Mineral Density (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 para-thyroid hormone (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:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 45 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
- •RA will be defined according to the 2010 American College of Rheumatology/European League Against Rheumatism diagnostic and classification criteria.
- •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
- •A switch in DMARD in the last 3 months;
- •Current use of chronic oral glucocorticoids > 5 milligrams per day;
- •A prior history of intolerance to teriparatide;
- •T-score < -2.5 or a prior minimal trauma fracture;
- •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);
- •History of significant cardiac, hepatic, current alcohol abuse, or major psychiatric disorders;
- •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;
- •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;
- •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;
- •Patients who have had external beam radiation; and
- •Patients currently on digoxin.
- •Women that are currently pregnant or breast-feeding or plan on becoming pregnant over the course of participation in the study
Arms & Interventions
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.
Intervention: Teriparatide (Drug)
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.
Intervention: calcium citrate (Drug)
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.
Intervention: Vitamin D (Drug)
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.
Intervention: TNF antagonist (Drug)
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.
Intervention: calcium citrate (Drug)
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.
Intervention: Vitamin D (Drug)
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.
Intervention: TNF antagonist (Drug)
Outcomes
Primary Outcomes
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 Outcomes
- Change From Baseline in Disease Activity Score 28 Joint Count C-Reactive Protein (DAS-28 CRP)(Baseline and Month 12)
- Change From Baseline in Bone Mineral Density (BMD) Measured by Dual-Energy X-ray Absorptiometry (DXA) and Instant Vertebral Assessment (IVA) Scan(Baseline and Month 12)
Investigators
Daniel H. Solomon, M.D.,MPH
Principal Investigator
Brigham and Women's Hospital