Clinical trial NCT04522622: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Adynamic Bone Disease
Chronic Kidney Diseases
Cardiac Disease
Chronic Kidney Disease-Mineral and Bone Disorder
Keywords: Fracture risk
Teriparatide
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
name: Steno Diabetes Center Copenhagen
name: Rigshospitalet, Denmark
name: Aalborg University Hospital
First posted: 2020-08-21
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Changes in bone specific alkaline phosphatase (BSAP)
timeFrame: Baseline and 18 months
Secondary outcomes:
measure: Number of patients who no longer has adynamic bone disorder based on a BSAP >21 µg/l
timeFrame: Baseline and 18 months. It is also measured through study completion, an average of 30 months
measure: BMD at the lumbar spine, antebrachium, femoral neck and total hip
timeFrame: Baseline and 18 months. The scan is also performed at 30 months
measure: Incidence of fragility fractures and vertebral fractures assessed using x-ray of columna or vertebral fracture assessment (VFA)
timeFrame: Baseline and 18 months. The scan is also performed at 30 months
measure: Bone microarchitecture assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT)
timeFrame: Baseline and 12 months
measure: Volumetric BMD assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT)
timeFrame: Baseline and 12 months
measure: Bone geometry assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT)
timeFrame: Baseline and 12 months
measure: Bone strength assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT)
timeFrame: Baseline and 12 months
measure: Regional bone formation using 18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography (18F-NAF PET/CT)
timeFrame: Baseline and 12 months
measure: Changes in p-PTH
timeFrame: Baseline and 18 months. Some of them are also measured during follow up.
measure: Changes in p-phosphate
timeFrame: Baseline and 18 months. Some of them are also measured during follow up.
measure: Changes in p-magnesium
timeFrame: Baseline and 18 months. Some of them are also measured during follow up.
measure: Changes in calcium
timeFrame: Baseline and 18 months. Some of them are also measured during follow up.
measure: Bone histomorphometry
timeFrame: 12 months
measure: Changes in Intact Procollagen type 1 N-terminal Propeptide (P1NP)
timeFrame: Baseline and 18 months. They are also measured during follow up
measure: Changes in total P1NP
timeFrame: Baseline and 18 months. They are also measured during follow up
measure: Changes in Tartrate-Resistant Acid Phosphatase 5b (TRAP5b)
timeFrame: Baseline and 18 months. They are also measured during follow up
measure: Changes in sclerostin
timeFrame: Baseline and 18 months. They are also measured during follow up
measure: Changes in Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL)
timeFrame: Baseline and 18 months. They are also measured during follow up
measure: Changes in Osteoprotegerin (OPG)
timeFrame: Baseline and 18 months. They are also measured during follow up
measure: Changes in Fibroblast Growth Factor 23 (FGF-23)
timeFrame: Baseline and 18 months. They are also measured during follow up
measure: 24-hour blood pressure
timeFrame: Baseline and 18 months
measure: Pulse wave measurements including velocity
timeFrame: Baseline and 18 months
measure: Changes in cardiovascular marker Calciprotein Particles (CPP)/T50
timeFrame: Baseline and 18 months
measure: Changes in cardiovascular marker N-Terminal pro B-type Natriuretic Peptide (NT-proBNP)
timeFrame: Baseline and 18 months
measure: Adverse reactions
timeFrame: From baseline to 18 months
measure: Bone microstructure
timeFrame: 12 months
measure: Bone histology
timeFrame: 12 months
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Gentofte
country: Denmark
facility: Steno Diabetes Center Copenhagen
city: Herlev
country: Denmark
facility: Herlev and Gentofte Hospital, Herlev Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Department of Nephrology, Herlev and Gentofte Hospital
name: Ditte Hansen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: