Treatment of Adynamic Bone Disorder With Parathyroid Hormone in Chronic Kidney Disease

Official title

Treatment of Adynamic Bone Disorder With Parathyroid Hormone in Patients With Chronic Kidney Disease

Overview

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.

Interventions

• Drug Teriparatide
  20 micrograms
• Diagnostic test DXA,VFA, X-ray, HR-pQCT, 18-F NAF PET/CT
  All participants undergo DXA and VFA or X-ray scans 3 times during the study. Some participants (those connected to Herlev) are offered 18F NAF PET/CT scans at baseline and after 12 months and some participants (those connected to Odense University Hospital and Aalborg University Hospital) are offered HR-pQCT scans at baseline and after 12 months. The 18F-NAF PET/CT and HR-pQCT are optional, so it is not a must to have these procedures done to participate in the study.
• Procedure Bone biopsy
  All participants are invited to undergo a bone biopsy after 12 months, but it is not a must to have the procedure done to participate in the study.
• Diagnostic test Cardiac tests
  All participants are invited to undergo 24-hour blood pressure measurements and pulse wave measurements at baseline and after 18 months, but it is not a must to have these procedures done to participate in the study.
• Other Blood and urine samples and physical examination
  All participants must undergo a physical examination and deliver blood and urine samples in order to participate in the study.

Primary outcome measures

• Changes in bone specific alkaline phosphatase (BSAP) [Time frame: Baseline and 18 months]

Secondary outcome measures (12)

• Number of patients who no longer has adynamic bone disorder based on a BSAP >21 µg/l [Time frame: 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 [Time frame: 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) [Time frame: Baseline and 18 months. The scan is also performed at 30 months]
• Bone microarchitecture assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) [Time frame: Baseline and 12 months]
• Volumetric BMD assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) [Time frame: Baseline and 12 months]
• Bone geometry assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) [Time frame: Baseline and 12 months]
• Bone strength assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) [Time frame: Baseline and 12 months]
• Regional bone formation using 18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography (18F-NAF PET/CT) [Time frame: Baseline and 12 months]
• Changes in p-PTH [Time frame: Baseline and 18 months. Some of them are also measured during follow up.]
• Changes in p-phosphate [Time frame: Baseline and 18 months. Some of them are also measured during follow up.]
• Changes in p-magnesium [Time frame: Baseline and 18 months. Some of them are also measured during follow up.]
• Changes in calcium [Time frame: Baseline and 18 months. Some of them are also measured during follow up.]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Denmark · 4 centers

• Aalborg University Hospital — Aalborg
• Steno Diabetes Center Copenhagen — Gentofte Municipality
• Herlev and Gentofte Hospital, Herlev Hospital — Herlev
• Odense University Hospital — Odense

Identifiers

NCT: NCT04522622 · DANDYNAMIC BONE · 2018-003888-56

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗