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

Phase 4RecruitingNCT04522622

Ditte Hansen48 enrolled

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Adynamic Bone Disease Chronic Kidney Diseases Cardiac Disease Chronic Kidney Disease-Mineral and Bone Disorder

Interventions

TeriparatideDRUG

20 micrograms

DXA,VFA, X-ray, HR-pQCT, 18-F NAF PET/CTDIAGNOSTIC_TEST

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.

Bone biopsyPROCEDURE

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 120 Years

Medical Language ↔ Plain English

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

Locations (4)

Aalborg University Hospital

Aalborg, Denmark

NOT_YET_RECRUITING

Steno Diabetes Center Copenhagen

Gentofte Municipality, Denmark

NOT_YET_RECRUITING

Herlev and Gentofte Hospital, Herlev Hospital

Herlev, Denmark

RECRUITING

Outcomes

Primary Outcomes

Changes in bone specific alkaline phosphatase (BSAP)

The difference between treated and controls in changes from baseline to 18 months in bone specific alkaline phosphatase

Time frame: Baseline and 18 months

Secondary Outcomes

Number of patients who no longer has adynamic bone disorder based on a BSAP >21 µg/l

Changes between baseline and 18 months as well as differences between treated and controls.

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

Changes between baseline and 18 months as well as differences between treated and controls

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)

Changes between baseline and 18 months as well as differences between treated and controls

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)

Changes between baseline and 12 months as well as differences between treated and controls. The HR-pQCT scan is a voluntary procedure.

Time frame: Baseline and 12 months

Volumetric BMD assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT)

Changes between baseline and 12 months as well as differences between treated and controls. The HR-pQCT scan is a voluntary procedure.

Central Contacts

Sabina C Hauge, MD

CONTACT

+4528965887 sabina.chaudhary.hauge@regionh.dk

Ditte Hansen, MD, PhD

CONTACT

+4538682056 ditte.hansen.04@regionh.dk

Data from ClinicalTrials.gov

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