Changes in cardiovascular calcification after denosumab in dialysis patients with secondary hyperparathyroidism and low bone mass

ISRCTN ISRCTN92563400
DOI https://doi.org/10.1186/ISRCTN92563400
Secondary identifying numbers KSC104-051
Submission date
02/10/2018
Registration date
01/11/2018
Last edited
09/08/2022
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Urological and Genital Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
In a previous study of the drug denosumab for the treatment of severe hyperparathyroidism (too much parathyroid hormone) in patients with low bone mass undergoing dialysis, patients could benefit from bone mass gain and bone pain relief. In dialysis patients, this drug is relatively safe because each dialysis session delivers calcium into the circulation. However, reportedly, calcium and active vitamin D given to prevent hypocalcemia (low blood calcium) can lead to ectopic calcification (calcium build up). Using appropriate calcium dialysate (dialysis fluid) to make total body calcium as balanced as possible, denosumab could cause bone mass gain and reduce soft tissue and vessel calcification. This study aims to recruit patients with end stage renal (kidney) disease with hyperparathyroidism and low bone mass. The goal is to find whether denosumab could slow coronary artery calcification in patients with hyperparathyroidism undergoing regular dialysis.

Who can participate?
Patients aged 18 and over with end stage renal disease with hyperparathyroidism and low bone mass

What does the study involve?
Participants are allocated to one of two groups by their wishes, to receive either denosumab or not. All participants attend for a CT scan of the heart to measure blood vessel calcification. Participants attend for a review at 6 months.

What are the possible benefits and risks of participating?
The participants could benefit from free CT scans to monitor their heart. The participants who receive denosumab are closely monitored during the dialysis process. However, there could still be a risk of hypocalcemia.

Where is the study run from?
Kaohsiung Veterans General Hospital (Taiwan)

When is the study starting and how long is it expected to run for?
September 2013 to August 2018

Who is funding the study?
Kaohsiung Veterans General Hospital (Taiwan)

Who is the main contact?
Dr Chien-Liang Chen
cclchen@seed.net.tw

Contact information

Dr Chien-Liang Chen
Scientific

386-Ta-Chung First section road
Kaohsiung City
81410
Taiwan

ORCiD logoORCID ID 0000-0002-9508-8396
Phone +886 (0)7 3422121 ext 2109
Email cclchen@seed.net.tw

Study information

Study designNon-randomised study
Primary study designInterventional
Secondary study designNon randomised study
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format
Scientific titleChanges in cardiovascular calcification after denosumab in dialysis patients with secondary hyperparathyroidism and low bone mass
Study objectivesThe effect of denosumab on vascular calcification in patients with chronic renal failure patients with low bone mass has been a subject of interest. The purpose of this investigation is to determine changes in vascular calcification after the administration of denosumab by using fast-gated helical computed axial tomographic imaging to measure coronary and abdomen aorta calcification.
Ethics approval(s)Kaohsiung V.G.H. Institutional Review Board, 17/09/2013, ref: VGHKS-CT18-CT8-19
Health condition(s) or problem(s) studiedPatients with ESRD undergoing dialysis with severe hyperparathyroidism and low bone mass
InterventionThe effect of denosumab on vascular calcification in patients with chronic renal failure patients with low bone mass has been a subject of interest. The purpose of this investigation is to determine changes in vascular calcification after the administration of denosumab by using fast-gated helical computed axial tomographic imaging to measure coronary and abdomen aorta calcification.

Participants are allocated to one of two groups by their wishes, to receive either 60 mg denosumab (denosumab group) or conventional treatment (control group). All participants have a screening visit combined with a baseline visit, and if happy to participate and they will attend for a CT scan of the heart at baseline and at the 6-month follow-up examination to determine bone mineral density and blood vessel calcification.
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase I
Drug / device / biological / vaccine name(s)Denosumab
Primary outcome measureCoronary and abdomen aorta calcification measured using fast-gated helical computed axial tomographic imaging at baseline and 6 months
Secondary outcome measuresOsteopenia measured using dual-energy X-ray absorptiometry (DEXA) at baseline and 6 months
Overall study start date17/09/2013
Completion date08/08/2018

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants21
Total final enrolment42
Key inclusion criteriaIn accordance with the regulatory guidelines, the patients were enrolled in the peritoneal dialysis or hemodialysis patient groups. Key inclusion criteria were age >18 years, normal laboratory tests at screening and baseline, and clinically acceptable physical examination and electrocardiograph results at screening. The study protocol was therefore amended to include requirements for daily supplementation of calcium and calcitriol according to standard dialysis guideline in all subjects with ESRD with low bone mass and a history of iPTH>800 pg/mL. All of the patients had been receiving renal replacement therapy, had various degrees of osteopenia with bone mineral densities, which were measured by dual-energy X-ray absorptiometry (DEXA); furthermore, all patients had a forearm, femoral neck or lumbar spine T score lower than -2.5 SD, indicative of low bone mass.
Key exclusion criteriaKey exclusion criteria were known sensitivity to any study treatment, unstable medical condition, history of malignancy, active infection, pregnancy, lactation, nursing, parathyroidectomy with parathyromatosis, drug abuse at screening, and aluminum levels >20 µg/L
Date of first enrolment08/10/2013
Date of final enrolment16/09/2016

Locations

Countries of recruitment

  • Taiwan

Study participating centre

Kaohsiung Veterans General Hospital
386 Ta-chung first section road
Kaohsiung City
81410
Taiwan

Sponsor information

Kaohsiung Veterans General Hospital
Hospital/treatment centre

386 Ta-chung First Road
Kaohsiung City
81410
Taiwan

Phone +886 (0)7 3422121 ext 2109 or +886 (0)975581961
Email cclchen@seed.net.tw
Website https://www.vghks.gov.tw/
ROR logo "ROR" https://ror.org/04jedda80

Funders

Funder type

Hospital/treatment centre

Kaohsiung Veterans General Hospital, VGHKS 104-051 and VGHKS105-080

No information available

Results and Publications

Intention to publish date31/12/2018
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planSubmission to journal
IPD sharing planThe datasets generated during and/or analysed during the current study are/will be available upon request from Dr Chien-Liang Chen (cclchen1@vghks.gov.tw).

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol file 09/08/2022 No No
Results article 01/08/2020 09/08/2022 Yes No

Additional files

35808 Protocol.pdf

Editorial Notes

09/08/2022: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
3. Uploaded protocol (not peer-reviewed) as an additional file.