Treatment of Adynamic Bone Disorder With Parathyroid Hormone in Chronic Kidney Disease
- Conditions
- Cardiac DiseaseAdynamic Bone DiseaseChronic Kidney Disease-Mineral and Bone DisorderChronic Kidney Diseases
- Interventions
- Diagnostic Test: DXA,VFA, X-ray, HR-pQCT, 18-F NAF PET/CTProcedure: Bone biopsyDiagnostic Test: Cardiac testsOther: Blood and urine samples and physical examination
- Registration Number
- NCT04522622
- Lead Sponsor
- Ditte Hansen
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 48
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Teriparatide Bone biopsy Patients receive teriparatide 20 micrograms once daily for 18 months Teriparatide Blood and urine samples and physical examination Patients receive teriparatide 20 micrograms once daily for 18 months Controls DXA,VFA, X-ray, HR-pQCT, 18-F NAF PET/CT Controls receive no treatment with teriparatide Controls Bone biopsy Controls receive no treatment with teriparatide Teriparatide DXA,VFA, X-ray, HR-pQCT, 18-F NAF PET/CT Patients receive teriparatide 20 micrograms once daily for 18 months Teriparatide Cardiac tests Patients receive teriparatide 20 micrograms once daily for 18 months Controls Cardiac tests Controls receive no treatment with teriparatide Controls Blood and urine samples and physical examination Controls receive no treatment with teriparatide Teriparatide Teriparatide Patients receive teriparatide 20 micrograms once daily for 18 months
- Primary Outcome Measures
Name Time Method Changes in bone specific alkaline phosphatase (BSAP) Baseline and 18 months The difference between treated and controls in changes from baseline to 18 months in bone specific alkaline phosphatase
- Secondary Outcome Measures
Name Time Method 24-hour blood pressure Baseline and 18 months Changes between baseline and 18 months as well as differences between treated and controls. These are voluntary procedures.
Pulse wave measurements including velocity Baseline and 18 months Changes between baseline and 18 months as well as differences between treated and controls. These are voluntary procedures.
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 Changes between baseline and 18 months as well as differences between treated and controls.
BMD at the lumbar spine, antebrachium, femoral neck and total hip Baseline and 18 months. The scan is also performed at 30 months Changes between baseline and 18 months as well as differences between treated and controls
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 Changes between baseline and 18 months as well as differences between treated and controls
Bone microarchitecture assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) Baseline and 12 months Changes between baseline and 12 months as well as differences between treated and controls. The HR-pQCT scan is a voluntary procedure.
Bone geometry assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) Baseline and 12 months Changes between baseline and 12 months as well as differences between treated and controls. The HR-pQCT scan is a voluntary procedure.
Regional bone formation using 18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography (18F-NAF PET/CT) Baseline and 12 months Changes between baseline and 12 months as well as differences between treated and controls. The 18F-NAF PET/CT is a voluntary procedure.
Changes in p-magnesium Baseline and 18 months. Some of them are also measured during follow up. Changes between baseline and 18 months as well as differences between treated and controls.
Changes in calcium Baseline and 18 months. Some of them are also measured during follow up. P-ionised calcium. Changes between baseline and 18 months as well as differences between treated and controls.
Volumetric BMD assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) Baseline and 12 months Changes between baseline and 12 months as well as differences between treated and controls. The HR-pQCT scan is a voluntary procedure.
Changes in p-phosphate Baseline and 18 months. Some of them are also measured during follow up. Changes between baseline and 18 months as well as differences between treated and controls.
Bone histomorphometry 12 months Static and dynamic bone histomorphometry classified by the bone Turnover Mineralization Volume (TMV) classification assessed by bone biopsy. Performed after 12 months. This is a voluntary procedure.
Changes in sclerostin Baseline and 18 months. They are also measured during follow up Changes between baseline and 18 months as well as differences between treated and controls.
Changes in Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL) Baseline and 18 months. They are also measured during follow up Changes between baseline and 18 months as well as differences between treated and controls.
Changes in Osteoprotegerin (OPG) Baseline and 18 months. They are also measured during follow up Changes between baseline and 18 months as well as differences between treated and controls.
Changes in cardiovascular marker N-Terminal pro B-type Natriuretic Peptide (NT-proBNP) Baseline and 18 months Changes between baseline and 18 months as well as differences between treated and controls.
Bone strength assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) Baseline and 12 months Changes between baseline and 12 months as well as differences between treated and controls. The HR-pQCT scan is a voluntary procedure.
Changes in p-PTH Baseline and 18 months. Some of them are also measured during follow up. Changes between baseline and 18 months as well as differences between treated and controls.
Changes in Intact Procollagen type 1 N-terminal Propeptide (P1NP) Baseline and 18 months. They are also measured during follow up Changes between baseline and 18 months as well as differences between treated and controls.
Changes in total P1NP Baseline and 18 months. They are also measured during follow up Changes between baseline and 18 months as well as differences between treated and controls.
Changes in Fibroblast Growth Factor 23 (FGF-23) Baseline and 18 months. They are also measured during follow up Changes between baseline and 18 months as well as differences between treated and controls.
Changes in cardiovascular marker Calciprotein Particles (CPP)/T50 Baseline and 18 months Changes between baseline and 18 months as well as differences between treated and controls.
Adverse reactions From baseline to 18 months The incidence of adverse reactions in treated patients. This is examined during the entire study.
Changes in Tartrate-Resistant Acid Phosphatase 5b (TRAP5b) Baseline and 18 months. They are also measured during follow up Changes between baseline and 18 months as well as differences between treated and controls.
Bone histology 12 months Detailed histology of underlying cellular mechanisms using a combination of immunostainings and advanced in situ hybridizations on the bone biopsy
Bone microstructure 12 months Bone mictrostructure by micro-compyter tomography of the bone biopsy
Trial Locations
- Locations (4)
Aalborg University Hospital
🇩🇰Aalborg, Denmark
Steno Diabetes Center Copenhagen
🇩🇰Gentofte, Denmark
Herlev and Gentofte Hospital, Herlev Hospital
🇩🇰Herlev, Denmark
Odense University Hospital
🇩🇰Odense, Denmark