Randomized controlled trial comparing the efficacy of teriparatide, zoledronate and denosumab in postmenopausal women with type 2 diabetes mellitus at high risk of fragility fractures: a pilot study.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- 1. To assess the percent change in BMD at the lumbar spine and femoral neck at the end of intervention
研究概览
简要总结
This study is a randomized, parallel group, multiple arm, single centered trial comparing the efficacy of teriparatide, zoledronate and denosumab, where every consecutive postmenopausal women diagnosed with type 2 DM attending the endocrinology clinic at PGIMER, Chandigarh would be screened for possible inclusion in study. Those fulfilling the criteria would be randomized into 4 groups in 1:1:1:1 ratio. Group A (n=30) would receive injection teriparatide daily, Group B (n=30) would receive injection zoledronate 5mg once yearly, Group C (n=30) would receive injection denosumab 60mg every 6 months, along with calcium and vitamin D supplements. Group D (n=30) would receive only calcium and vitamin D supplements. The primary outcome would be to assess the percent change in BMD at lumbar spine and femoral neck and frequency of incident clinical major osteoporotic and/or morphometric vertebral fragility fractures. Secondary outcomes will be to assess the change in BMD at distal radius, trabecular bone score, HR-pQCT (high-resolution peripheral quantitative computed tomography) parameters and bone turnover markers at the end of intervention and also to assess short-term change in glycemic control with anti-osteoporotic treatment.
Trial is open to recruitment and as of date, 27-08-2022, 88 participants have recruited with 22 participants in each group and we have been following them as mentioned in the protocol.
No serious adverse events noted so far.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Outcome Assessor Blinded
入排标准
- 年龄范围
- 50.00 Year(s) 至 90.00 Year(s)（—）
- 性别
- Female
入选标准
- •Ambulatory type 2 diabetes mellitus postmenopausal females
- •Age more than or equal to 50 years
- •Postmenopausal status for at least 5 years
- •Duration of type 2 diabetes mellitus at least 5 years
- •Baseline eGFR more than or equal to 45 ml/min/1.73 m2
- •Baseline HbA1c 7-10%
- •Prior vertebral (clinical or morphometric), hip, radius, humerus fragility fracture OR
- •Baseline BMD T-score at lumbar spine or femoral neck less than or equal to -2.5 (corrected for T2D) and baseline FRAX score (corrected for T2D) indicating a 10-year probability of hip fracture more than or equal to 2.5% or of major osteoporotic fracture more than or equal to 9%.
- •Those willing to give informed consent.
排除标准
- •Type 1 diabetes mellitus or latent autoimmune diabetes in adults, or secondary diabetes mellitus
- •Prior history of use of bone-active therapies (bisphosphonates, teriparatide, denosumab, selective estrogen receptor modulators, hormone replacement therapies, calcitonin)
- •Prior history of glucocorticoid use at a dose more than or equal to 15 mg (prednisolone or equivalent) for more than or equal to 3 months.
- •History of use of pioglitazone, thiazides, or canagliflozin over last 6 months
- •Hyperthyroidism (overt/subclinical) or overt hypothyroidism (detected during baseline screening)
- •History of hypoparathyroidism or primary hyperparathyroidism
- •History of acromegaly
- •History of Addison disease or Cushing’s syndrome
- •History of gonadal insufficiency (primary or secondary)
- •History of hypercalcemia (or detected during baseline screening)
- •Elevated hepatic transaminase levels more than or equal to 3 times upper limit of normal (detected during baseline screening)
- •Any solid organ or bone marrow transplant
- •History of any active or past malignancy
- •History of gastrointestinal disorders and malabsorption states, namely, celiac disease (also screened at baseline), inflammatory bowel disease, chronic hepatitis, bowel resection, chronic liver disease, gastrectomy, lactose intolerance
- •History of bone marrow related disorders, namely, leukemia, lymphoma, hemochromatosis, multiple myeloma (also screened at baseline), sarcoidosis, sickle cell anemia, thalassemia, amyloidosis
- •History of rheumatological disorders, namely, rheumatoid arthritis, ankylosing spondylitis, Marfans syndrome, Ehler-Danlos syndrome
- •History of any condition that may affect bone metabolism, namely, Paget’s disease, osteopetrosis, osteogenesis imperfecta, hypophosphatasia
- •History of recent tooth extraction (within 6 months of screening).
结局指标
主要结局
1. To assess the percent change in BMD at the lumbar spine and femoral neck at the end of intervention
时间窗: 18 months
2. To assess the frequency of incident clinical major osteoporotic fractures (fragility) and/or morphometric vertebral fractures (fragility) during intervention
时间窗: 18 months
次要结局
- 1. To assess the percent change in BMD at the 33% radius at the end of intervention(2. To assess the change in trabecular bone score (TBS) at the end of intervention)