Treatment of Primary Hyperparathyroidism With Denosumab and Cinacalcet.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Percentage Change in 1/3 Forearm Bone Mineral Density
研究概览
简要总结
The only known cure for primary hyperparathyroidism is surgical removal of one or more parathyroid glands. Some patients however, do not fulfill criteria for surgery or do not want to undergo a procedure due to fear of the associated risks. Therefore a medical alternative is warranted.
This study aims to evaluate the effects of Denosumab alone, and in combination with Cinacalcet, as a medical treatment for patients suffering from primary hyperparathyroidism, with mild osteoporosis. To the best of our knowledge no previously reported randomized controlled trial has investigated the use of denosumab in primary hyperparathyroidism.
60 patients will be enrolled in three different treatment-groups: 20 receiving both Denosumab and Cinacalcet, 20 Denosumab and placebo and 20 placebo and placebo. Patients included do not meet the criteria for, or have no wish for a surgical procedure.
By combining the two drugs, this study could possibly contribute to the discovery of a realistic medical alternative to surgery. It is expected that the therapy will be able to both control s-calcium and s-intact parathyroid hormone (iPTH), and simultaneously enhance bone-structure. The therapy thus has the potential of preventing fractures and possibly other long-term effects of primary hyperparathyroidism such as formation of kidney stones, and coronary calcification. Another objective of this project is to investigate whether the combined therapy can facilitate an actual reset of the Calcium-sensing receptor, and thereby de facto cure the disease.
详细描述
Background/Context:
This project deals with medical treatment of primary hyperparathyroidism. The only cure currently available is surgical removal of one or more parathyroid glands, but this option is neither feasible, nor desirable in all patients with the diagnosis.
Today a major group of patients are being diagnosed by coincidence with biochemical blood-screening, and are therefore in an asymptomatic state of the disease at the time of diagnosis. Long term studies show that these patients over time often have progression in their disease, and develop complications such as osteoporosis. Thus a medical alternative is warranted.
Previous studies have investigated the effects of well known antiresorptive drugs such as bisphosphonates, as well as estrogen-related compounds. These drugs have had effects on particularly bone mineral density (BMD) and biochemical bone-turnover markers, but have been able only transiently to lower blood-calcium levels. Combined with too many unwanted side-effects and a high prevalence of contraindications for a large proportion of the patients needing treatment, these drugs have not provided a realistic alternative to surgery.
Treatment today generally follows the international consensus for treatment of asymptomatic patients with primary hyperparathyroidism. Briefly this includes watchful waiting with biannual control-sessions for indication of surgery, screening for kidney stones/nephrolithiasis, osteoporosis and s-calcium - and s-iPTH levels.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women of 18 years of age or older.
- •T-score by Dual X-ray Absorptiometry (DXA) between -1,0 og -3,5
- •Patients from The North Jutland Region diagnosed with primary hyperparathyroidism at the Department of Endocrinology, Aalborg University Hospital. (Hypercalcaemia measured at two different time-points and simultaneous elevated/inappropriately high PTH, and exclusion of differential diagnosis.)
排除标准
- •Medical history of diseases leading to hypercalcaemia other than Primary Hyperparathyroidism.
- •Patients being treated with Denosumab or Cinacalcet prior to inclusion or previously treated with Denosumab or Cinacalcet.
- •Moderately - Severely decreased liver function (alanine aminotransferase >250u/l, gamma-glutamyl transferase>150u/l, Bilirubin >30)
- •Acute myocardial infarction or apoplexia in the 3 months before inclusion.
- •Medical record of heart failure
- •Risk factors of prolonged corrected QT interval (QTc).
- •Open lesions from oral surgery.
- •Primary diseases of the bone other than osteoporosis.
- •Patients suffering from kidney disease or renal failure.
- •Patients under treatment with thiazide or lithium.
- •Medical record of generalized seizures or epilepsy.
- •Active malignant disease.
- •Known allergies towards the specified medicinal products (IMPs).
- •Pregnancy or breastfeeding.
- •Fertile women who do not agree to the usage of effective contraception.
- •Other circumstances, evaluated by the responsible investigator, making the subject unsuitable for participation.
研究组 & 干预措施
Combined treatment.
20 subjects will be treated with combined 60mg denosumab bi-annually , 30 mg cinacalcet daily and 50 micrograms vitamin-D daily.
干预措施: Cinacalcet 30 mg Tablet (Drug)
Combined treatment.
20 subjects will be treated with combined 60mg denosumab bi-annually , 30 mg cinacalcet daily and 50 micrograms vitamin-D daily.
干预措施: Denosumab Inj 60 mg/ml (Drug)
Monotherapy
20 subjects will receive 60mg denosumab bi-annually, placebo and 50 micrograms vitamin-D daily.
干预措施: Denosumab Inj 60 mg/ml (Drug)
Monotherapy
20 subjects will receive 60mg denosumab bi-annually, placebo and 50 micrograms vitamin-D daily.
干预措施: Placebo tablets (Other)
Placebo
20 subjects will receive a saline injection bi-annually (blinded), placebo-tablets and 50 micrograms vitamin-D daily.
干预措施: Placebo tablets (Other)
Placebo
20 subjects will receive a saline injection bi-annually (blinded), placebo-tablets and 50 micrograms vitamin-D daily.
干预措施: Saline Injection (Placebo) (Other)
结局指标
主要结局
Percentage Change in 1/3 Forearm Bone Mineral Density
时间窗: Baseline,one year
Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
Change in Total Hip Bone Mineral Density
时间窗: Baseline,one year
Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
Change in Femoral Neck Bone Mineral Density
时间窗: Baseline,one year
Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
Percentage Change in Lumbar Spine Bone Mineral Density
时间窗: Baseline,one year
Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
Percentage Change in Total Hip Bone Mineral Density
时间窗: Baseline,one year
Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
Change in Lumbar Spine Bone Mineral Density
时间窗: Baseline,one year
Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
Change in 1/3 Forearm Bone Mineral Density
时间窗: Baseline,one year
Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
Percentage Change in Femoral Neck Bone Mineral Density
时间窗: Baseline,one year
Percentage change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
次要结局
- Percent Change From Baseline in P-carboxy-terminal Collagen Crosslinks (CTX)(Change from baseline at 48 weeks reported.)
- Change MDI-score(Baseline, 6 mths, one year.)
- Bone Mineral Content(Baseline, one year)
- Percentage Change in Volumetric BMD for the Lumbar Spine.(Baseline, one year)
- Change in Volumetric BMD for the Lumbar Spine.(Baseline, one year)
- Vertebral Fracture Assessment - Final Scan(Patients with vertebral fractures at one year reported.)
- Change in Cortical Width.(Baseline, one year.)
- Mean P-calcium During Treatment.(Monthly up to one year.)
- Patients With Nephrolithiasis Final Scan.(Patients with nephrolithiasis at one year reported.)
- Change in Volumetric BMD for the Distal Forearm.(Baseline, one year)
- Median Agatstons Score Final(Baseline, one year)
- Reset of the Calcium Sensing Receptor?(2 weeks after termination of medication.)
- Adverse Reactions.(Monthly up to one year.)
- Patients With Pancreas-calcifications Final Scan.(Patients with pancreas-calcifications at one year reported.)
- Mean p-PTH During Treatment.(Monthly up to one year.)
- Mean p-Phosphate During Treatment.(Monthly up to one year.)
- Percent Change From Baseline in p-N-terminal Propeptide of Type I Procollagen (p-P1NP).(Change from baseline at 48 weeks reported.)
- Percentage Change in Volumetric BMD for the Distal Forearm.(Baseline, one year)
- Percent Change From Baseline in P-osteocalcin.(Change from baseline at 48 weeks reported.)
- Percent Change From Baseline in S-bone-specific Alkaline Phosphatase (BAP).(Change from baseline at 48 weeks reported.)
- Percent Change From Baseline in p-Tartrate-resistant Acid Phosphatase 5b (Trap5b).(Change from baseline at 48 weeks reported.)
- Percent Change From Baseline in p-Sclerostin.(Change from baseline at 48 weeks reported.)
- Percent Change From Baseline in P-fibroblast Growth Factor 23 (FGF23).(Change from baseline at 48 weeks reported.)
- Changes in p-25-vitamin D(Change from baseline at 48 weeks reported.)
- Changes in s-1,25-vitamin D(Change from baseline at 48 weeks reported.)
- Patients With Nephrocalcinosis, Final Scan.(Baseline, one year)
研究者
Peter Vestergaard
Professor, DMSc, Consultant
Aalborg University Hospital