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

Treatment of Adynamic Bone Disorder With Parathyroid Hormone 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 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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases; Cardiac Disease; Chronic Kidney Disease-Mineral and Bone Disorder; Adynamic Bone Disease
• Intervention / Treatment: Drug: Teriparatide; Diagnostic test: Cardiac tests; Other: Blood and urine samples and physical examination; Diagnostic test: DXA,VFA, X-ray, HR-pQCT, 18-F NAF PET/CT; Procedure: Bone biopsy

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.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sabina C Hauge, MD; Phone Number: +4528965887; Email: sabina.chaudhary.hauge@regionh.dk
• Study Contact Backup: Name: Ditte Hansen, MD, PhD; Phone Number: +4538682056; Email: ditte.hansen.04@regionh.dk

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Not yet recruiting
    • Aalborg University Hospital
    • Contact: Charlotte Strandhave, MD, PhD; Phone Number: +4597665500; Email: charlotte.strandhave@rn.dk
    • Contact: My HS Svensson, MD, PhD; Phone Number: +4597665500; Email: my.svensson@rn.dk
    • Principal Investigator: Charlotte Strandhave, MD, PhD
    • Sub-Investigator: Peter Vestergaard, MD, PhD
    • Sub-Investigator: My HS Svensson, MD, PhD
  • Gentofte, Denmark, 2820
    • Not yet recruiting
    • Steno Diabetes Center Copenhagen
    • Contact: Frederik Persson, MD, DMSc; Phone Number: +4539680800; Email: frederik.persson@regionh.dk
    • Principal Investigator: Frederik Persson, MD, DMSc.
  • Herlev, Denmark, 2730
    • Recruiting
    • Herlev and Gentofte Hospital, Herlev Hospital
    • Principal Investigator: Ditte Hansen, MD, PhD
    • Sub-Investigator: Sabina C Hauge, MD
    • Contact: Sabina C Hauge, MD; Phone Number: +4528965887; Email: sabina.chaudhary.hauge@regionh.dk
    • Contact: Ditte Hansen, MD, PhD; Phone Number: +4538682056; Email: ditte.hansen.04@regionh.dk
    • Sub-Investigator: Jakob P Holm, MD, PhD
  • Odense, Denmark, 5000
    • Not yet recruiting
    • Odense University Hospital
    • Contact: Morten F Nielsen, MD, PhD; Phone Number: +4522877448; Email: mmfnielsen@health.sdu.dk
    • Contact: Subagini Nagarajah, MD; Phone Number: +4528598621; Email: subagininagarajah3@rsyd.dk
    • Principal Investigator: Morten F Nielsen, MD, PhD
    • Sub-Investigator: Subagini Nagarajah, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Teriparatide; Patients receive teriparatide 20 micrograms once daily for 18 months	Drug: Teriparatide; 20 micrograms; Other Names: Terrosa; 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.; 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.
Other: Controls; Controls receive no treatment with teriparatide	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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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.
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.
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.
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.
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
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
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
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
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
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
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
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
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
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
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
Adverse reactions	The incidence of adverse reactions in treated patients. This is examined during the entire study.	From baseline to 18 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	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.	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.	Baseline and 12 months
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
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
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
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
Bone microstructure	Bone mictrostructure by micro-compyter tomography of the bone biopsy	12 months
Bone histology	Detailed histology of underlying cellular mechanisms using a combination of immunostainings and advanced in situ hybridizations on the bone biopsy	12 months

Collaborators and Investigators

• Sponsor: Ditte Hansen
• Collaborators: Odense University Hospital; Rigshospitalet, Denmark; Steno Diabetes Center Copenhagen; Aalborg University Hospital
• Investigators: Principal Investigator: Ditte Hansen, MD, PhD, Department of Nephrology, Herlev and Gentofte Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: August 13, 2020
• First Submitted That Met QC Criteria: August 19, 2020
• First Posted (Actual): August 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Teriparatide; Fracture risk
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Disease Attributes; Renal Insufficiency; Nutrition Disorders; Musculoskeletal Diseases; Parathyroid Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Bone Diseases, Metabolic; Calcium Metabolism Disorders; Rickets; Vitamin D Deficiency; Hyperparathyroidism, Secondary; Hyperparathyroidism; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Heart Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Bone Diseases; Chronic Kidney Disease-Mineral and Bone Disorder; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Teriparatide
• Other Study ID Numbers: DANDYNAMIC BONE; 2018-003888-56 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: As of now we have no plan to share Individual Participant Data (IPD) with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No