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

Chronic Kidney Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04522622
• Other study ID #: DANDYNAMIC BONE
• Secondary ID: 2018-003888-56
• Status: Recruiting
• Phase: Phase 4
• Start date: December 15, 2021
• Est. completion date: September 1, 2027

Study information

• Verified date: April 2024
• Source: Herlev Hospital
• Contact: Sabina C Hauge, MD
• Phone: +4528965887
• Email: sabina.chaudhary.hauge[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: September 1, 2027
• Est. primary completion date: September 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Adynamic Bone Disease
• Bone Diseases
• Cardiac Disease
• Chronic Kidney Disease-Mineral and Bone Disorder
• Chronic Kidney Diseases
• Heart Diseases
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

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.

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg
Denmark	Steno Diabetes Center Copenhagen	Gentofte
Denmark	Herlev and Gentofte Hospital, Herlev Hospital	Herlev
Denmark	Odense University Hospital	Odense

Sponsors (5)

Lead Sponsor	Collaborator
Ditte Hansen	Aalborg University Hospital, Odense University Hospital, Rigshospitalet, Denmark, Steno Diabetes Center Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Baseline and 18 months
Secondary	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.	Baseline and 18 months. It is also measured through study completion, an average of 30 months
Secondary	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	Baseline and 18 months. The scan is also performed at 30 months
Secondary	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	Baseline and 18 months. The scan is also performed at 30 months
Secondary	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.	Baseline and 12 months
Secondary	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.	Baseline and 12 months
Secondary	Bone geometry 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.	Baseline and 12 months
Secondary	Bone strength 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.	Baseline and 12 months
Secondary	Regional bone formation using 18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography (18F-NAF PET/CT)	Changes between baseline and 12 months as well as differences between treated and controls. The 18F-NAF PET/CT is a voluntary procedure.	Baseline and 12 months
Secondary	Changes in p-PTH	Changes between baseline and 18 months as well as differences between treated and controls.	Baseline and 18 months. Some of them are also measured during follow up.
Secondary	Changes in p-phosphate	Changes between baseline and 18 months as well as differences between treated and controls.	Baseline and 18 months. Some of them are also measured during follow up.
Secondary	Changes in p-magnesium	Changes between baseline and 18 months as well as differences between treated and controls.	Baseline and 18 months. Some of them are also measured during follow up.
Secondary	Changes in calcium	P-ionised calcium. Changes between baseline and 18 months as well as differences between treated and controls.	Baseline and 18 months. Some of them are also measured during follow up.
Secondary	Bone histomorphometry	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.	12 months
Secondary	Changes in Intact Procollagen type 1 N-terminal Propeptide (P1NP)	Changes between baseline and 18 months as well as differences between treated and controls.	Baseline and 18 months. They are also measured during follow up
Secondary	Changes in total P1NP	Changes between baseline and 18 months as well as differences between treated and controls.	Baseline and 18 months. They are also measured during follow up
Secondary	Changes in Tartrate-Resistant Acid Phosphatase 5b (TRAP5b)	Changes between baseline and 18 months as well as differences between treated and controls.	Baseline and 18 months. They are also measured during follow up
Secondary	Changes in sclerostin	Changes between baseline and 18 months as well as differences between treated and controls.	Baseline and 18 months. They are also measured during follow up
Secondary	Changes in Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL)	Changes between baseline and 18 months as well as differences between treated and controls.	Baseline and 18 months. They are also measured during follow up
Secondary	Changes in Osteoprotegerin (OPG)	Changes between baseline and 18 months as well as differences between treated and controls.	Baseline and 18 months. They are also measured during follow up
Secondary	Changes in Fibroblast Growth Factor 23 (FGF-23)	Changes between baseline and 18 months as well as differences between treated and controls.	Baseline and 18 months. They are also measured during follow up
Secondary	24-hour blood pressure	Changes between baseline and 18 months as well as differences between treated and controls. These are voluntary procedures.	Baseline and 18 months
Secondary	Pulse wave measurements including velocity	Changes between baseline and 18 months as well as differences between treated and controls. These are voluntary procedures.	Baseline and 18 months
Secondary	Changes in cardiovascular marker Calciprotein Particles (CPP)/T50	Changes between baseline and 18 months as well as differences between treated and controls.	Baseline and 18 months
Secondary	Changes in cardiovascular marker N-Terminal pro B-type Natriuretic Peptide (NT-proBNP)	Changes between baseline and 18 months as well as differences between treated and controls.	Baseline and 18 months
Secondary	Adverse reactions	The incidence of adverse reactions in treated patients. This is examined during the entire study.	From baseline to 18 months
Secondary	Bone microstructure	Bone mictrostructure by micro-compyter tomography of the bone biopsy	12 months
Secondary	Bone histology	Detailed histology of underlying cellular mechanisms using a combination of immunostainings and advanced in situ hybridizations on the bone biopsy	12 months