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

Ditte Hansen

Status and phase: Enrolling; Phase 4

Conditions: Chronic Kidney Diseases; Cardiac Disease; Chronic Kidney Disease-Mineral and Bone Disorder; Adynamic Bone Disease

Treatments: Procedure: Bone biopsy; Diagnostic Test: Cardiac tests; Drug: Teriparatide; Diagnostic Test: DXA,VFA, X-ray, HR-pQCT, 18-F NAF PET/CT; Other: Blood and urine samples and physical examination

Study type: Interventional

Funder types: Other

Identifiers

NCT04522622

DANDYNAMIC BONE

2018-003888-56 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 48 estimated patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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48 participants in 2 patient groups

Teriparatide

Experimental group

Description:

Patients receive teriparatide 20 micrograms once daily for 18 months

Treatment:

Diagnostic Test: DXA,VFA, X-ray, HR-pQCT, 18-F NAF PET/CT

Procedure: Bone biopsy

Diagnostic Test: Cardiac tests

Drug: Teriparatide

Other: Blood and urine samples and physical examination

Controls

Other group

Description:

Controls receive no treatment with teriparatide

Treatment:

Diagnostic Test: DXA,VFA, X-ray, HR-pQCT, 18-F NAF PET/CT

Procedure: Bone biopsy

Diagnostic Test: Cardiac tests

Other: Blood and urine samples and physical examination