Treatment of Adynamic Bone Disorder With Parathyroid Hormone in Patients With Chronic Kidney Disease
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 48
- 试验地点
- 4
- 主要终点
- Changes in bone specific alkaline phosphatase (BSAP)
研究概览
简要总结
This study is a 1:1 randomized controlled trial with an intervention for 18 months and a follow up period of 12 months. The purpose of the study is to assess the safety and efficacy of recombinant human parathyroid hormone for treatment of adynamic bone disorder in patients with chronic kidney disease.
详细描述
This study is a 1:1 randomized controlled trial with an intervention for 18 months and a follow up period of 12 months.
The study will explore if treatment with recombinant human parathyroid hormone (PTH) improves bone turnover and bone mineral density (BMD), and thereby prevents the high risk of fracture in patients with chronic kidney disease (CKD).
Disturbed bone metabolism is related to increased risk of cardiovascular disease in patients with CKD. This study also wishes to examine of treatment with recombinant PTH improves cardiovascular parameters.
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
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •CKD stage 4-5D (eGFR ≤29 ml/min) according to Kidney Disease Improving Global Outcomes(KDIGO) definition
- •DXA scan with a T-score at the total hip, femoral neck or lumbar spine (L1-4) ≤-2 (or Z-score ≤-2) in a minimum of 2 vertebraes (for patients with active oral prednisolone treatment ≥ 5 mg/day for minimum 3 months the T-score or Z-score limit i < -1) and/or former fragility fracture (vertebral, hip, for- or upper arm, ankle) assessed with VFA or x-ray of the columna
- •Patients with expected adynamic bone disorder, based on BSAP≤21 µg/l or biopsy-verified low bone turnover
排除标准
- •Hypercalcemia defined as sustained ionized calcium >1.35 mmol/l
- •Previous fracture withon the last 6 months *Patients may be rescreened after the 6 months
- •Previous calciphylaxis
- •Thyroid disturbances not adequately treated based on the opinion by the clinician *Patients may be rescreened after treatment optimization
- •Treatment with digoxin
- •Paget's disease or other metabolic bone disorders
- •Antiresorptive or bone anabolic medication during the last 24 months (for bisphosphonates it is only during the last 12 months)
- •Former or present malignant disease (except skin basal or planocellular carcinoma)
- •Previous external beam or implant radiation therapy to the skeleton
- •Patients who have undergone a kidney transplantation within the last 12 months
- •25 hydroxyvitamin D2 and D3 <50 nmol/l *Patients may be rescreened after correction
- •Inability to administer teriparatide
- •Reduced liver function *Alanine Aminotransferase (ALAT) >3x upper limit of normal or bilirubin > 2x upper limit of normal
- •Pregnancy, lactation or fertile women (post-menopausal females are not considered fertile) not using safe anticonception (the following contraceptive methods are considered appropriate: Intrauterine device (IUD) or hormonal anticontraceptive (oral contraceptives, implant, transdermal patches, vaginal ring or depot injection)).
- •Hypersensitivity to the active substance in teriparatide or to any of the excipients or content
- •Inability to provide informed consent
- •Medical conditions or treatments that may interfere with assessments of the outcomes of the trial
- •Drug or alcohol abuse
- •Unable to participate in a clinical study based on the judgement by the local investigator
- •For those participating in the bone biopsy procedure: 1) Hypersensitivity to any of the tetracyclines or to any of the excipients or content, 2) Treatment with anticoagulants (vitamin K antagonists, Non-vitamin K Antagonist Oral Anticoagulants (NOAC), unfractionated or low-molecular heparin or antiplatelet agents that, due to clinical indication can't be paused, 3) Disturbances in thrombosis and/or haemostasis
- •For those participating in pulse wave measurements: 1) Atrial fibrillation, 2) Aorta stenosis
研究组 & 干预措施
Teriparatide
Patients receive teriparatide 20 micrograms once daily for 18 months
干预措施: Bone biopsy (Procedure)
Teriparatide
Patients receive teriparatide 20 micrograms once daily for 18 months
干预措施: Teriparatide (Drug)
Teriparatide
Patients receive teriparatide 20 micrograms once daily for 18 months
干预措施: DXA,VFA, X-ray, HR-pQCT, 18-F NAF PET/CT (Diagnostic Test)
Teriparatide
Patients receive teriparatide 20 micrograms once daily for 18 months
干预措施: Cardiac tests (Diagnostic Test)
Teriparatide
Patients receive teriparatide 20 micrograms once daily for 18 months
干预措施: Blood and urine samples and physical examination (Other)
Controls
Controls receive no treatment with teriparatide
干预措施: DXA,VFA, X-ray, HR-pQCT, 18-F NAF PET/CT (Diagnostic Test)
Controls
Controls receive no treatment with teriparatide
干预措施: Bone biopsy (Procedure)
Controls
Controls receive no treatment with teriparatide
干预措施: Cardiac tests (Diagnostic Test)
Controls
Controls receive no treatment with teriparatide
干预措施: Blood and urine samples and physical examination (Other)
结局指标
主要结局
Changes in bone specific alkaline phosphatase (BSAP)
时间窗: Baseline and 18 months
The difference between treated and controls in changes from baseline to 18 months in bone specific alkaline phosphatase
次要结局
- Number of patients who no longer has adynamic bone disorder based on a BSAP >21 µg/l(Baseline and 18 months. It is also measured through study completion, an average of 30 months)
- BMD at the lumbar spine, antebrachium, femoral neck and total hip(Baseline and 18 months. The scan is also performed at 30 months)
- Incidence of fragility fractures and vertebral fractures assessed using x-ray of columna or vertebral fracture assessment (VFA)(Baseline and 18 months. The scan is also performed at 30 months)
- 24-hour blood pressure(Baseline and 18 months)
- Pulse wave measurements including velocity(Baseline and 18 months)
- Bone microarchitecture assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT)(Baseline and 12 months)
- Bone geometry assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT)(Baseline and 12 months)
- Regional bone formation using 18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography (18F-NAF PET/CT)(Baseline and 12 months)
- Changes in p-magnesium(Baseline and 18 months. Some of them are also measured during follow up.)
- Changes in calcium(Baseline and 18 months. Some of them are also measured during follow up.)
- Volumetric BMD assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT)(Baseline and 12 months)
- Changes in p-phosphate(Baseline and 18 months. Some of them are also measured during follow up.)
- Bone histomorphometry(12 months)
- Changes in sclerostin(Baseline and 18 months. They are also measured during follow up)
- Changes in Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL)(Baseline and 18 months. They are also measured during follow up)
- Changes in Osteoprotegerin (OPG)(Baseline and 18 months. They are also measured during follow up)
- Changes in cardiovascular marker N-Terminal pro B-type Natriuretic Peptide (NT-proBNP)(Baseline and 18 months)
- Bone strength assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT)(Baseline and 12 months)
- Changes in p-PTH(Baseline and 18 months. Some of them are also measured during follow up.)
- Changes in Intact Procollagen type 1 N-terminal Propeptide (P1NP)(Baseline and 18 months. They are also measured during follow up)
- Changes in total P1NP(Baseline and 18 months. They are also measured during follow up)
- Changes in Fibroblast Growth Factor 23 (FGF-23)(Baseline and 18 months. They are also measured during follow up)
- Changes in cardiovascular marker Calciprotein Particles (CPP)/T50(Baseline and 18 months)
- Adverse reactions(From baseline to 18 months)
- Changes in Tartrate-Resistant Acid Phosphatase 5b (TRAP5b)(Baseline and 18 months. They are also measured during follow up)
- Bone histology(12 months)
- Bone microstructure(12 months)
研究者
Ditte Hansen
MD, PhD
Herlev Hospital