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

NCT04522622 | Recruiting Phase 4 DMC

• 2 other identifiers: DANDYNAMIC BONE2018-003888-56
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

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.

Conditions

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

Keywords

Fracture risk; Teriparatide

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (27)

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

  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

  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)

  Baseline and 18 months. The scan is also performed at 30 months

• Bone microarchitecture assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT)

  Baseline and 12 months

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

  Baseline and 12 months

Study Arms (2)

Teriparatide

EXPERIMENTAL

Patients receive teriparatide 20 micrograms once daily for 18 months

Drug: Teriparatide; 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

Controls

OTHER

Controls receive no treatment with teriparatide

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

Interventions

Teriparatide DRUG

20 micrograms

Also known as: Terrosa

Teriparatide

DXA,VFA, X-ray, HR-pQCT, 18-F NAF PET/CT DIAGNOSTIC_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.

Controls; Teriparatide

Bone biopsy PROCEDURE

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.

Controls; Teriparatide

Cardiac tests DIAGNOSTIC_TEST

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.

Controls; Teriparatide

Blood and urine samples and physical examination OTHER

All participants must undergo a physical examination and deliver blood and urine samples in order to participate in the study.

Controls; Teriparatide

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Ditte Hansen: lead
• Odense University Hospital: collaborator
• Steno Diabetes Center Copenhagen: collaborator
• Rigshospitalet, Denmark: collaborator
• Aalborg University Hospital: collaborator

Study Sites (4)

Aalborg University Hospital

Aalborg, 9000, Denmark

NOT YET RECRUITING

Steno Diabetes Center Copenhagen

Gentofte Municipality, 2820, Denmark

NOT YET RECRUITING

Herlev and Gentofte Hospital, Herlev Hospital

Herlev, 2730, Denmark

RECRUITING

Odense University Hospital

Odense, 5000, Denmark

NOT YET RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Heart Diseases; Chronic Kidney Disease-Mineral and Bone Disorder

Interventions

Teriparatide; X-Rays; Heart Function Tests; Blood Specimen Collection; Restraint, Physical

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cardiovascular Diseases; Rickets; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Hyperparathyroidism, Secondary; Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Parathyroid Hormone; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Investigative Techniques; Behavior Control; Therapeutics; Immobilization

Study Officials

• Ditte Hansen, MD, PhD

  Department of Nephrology, Herlev and Gentofte Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sabina C Hauge, MD

CONTACT

+4528965887; sabina.chaudhary.hauge@regionh.dk

Ditte Hansen, MD, PhD

CONTACT

+4538682056; ditte.hansen.04@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: August 13, 2020
• First Posted: August 21, 2020
• Study Start: December 15, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (4)