Bisphosphonate Prior to Parathyroidectomy in Primary Hyperparathyroidism

NCT06859580 | Recruiting Phase 4 DMC

• 3 other identifiers: ZOLPHPT2024-520073-13-002023-000007-39
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, double-blinded, placebo-controlled trial investigating the effects of zoledronic acid (ZOL) versus placebo in patients with primary hyperparathyroidism (PHPT) undergoing parathyroidectomy (PTX). PHPT is a common endocrine disorder associated with hypercalcemia, reduced bone mineral density (BMD), increased fracture risk, renal calcifications, and cardiovascular complications. While PTX remains the definitive treatment, the potential role of bisphosphonates in optimizing post-surgical outcomes remains unclear. This trial aims to evaluate whether a single infusion of ZOL prior to PTX impacts bone health, cardiovascular parameters, and renal function one year post-surgery. The primary endpoint is the change in areal bone mineral density (aBMD) at the lumbar spine one year after PTX. Secondary endpoints include changes in aBMD at other skeletal sites, volumetric BMD, bone microarchitecture, bone turnover markers, coronary artery calcium score, arterial stiffness, and renal calcifications. A total of 140 postmenopausal women and men over 50 years with PHPT and low BMD will be enrolled and randomized to receive either ZOL or placebo 2-4 weeks before PTX. Participants will undergo extensive imaging, biochemical analysis, and cardiovascular assessments at baseline and one year post-surgery. This study seeks to clarify whether ZOL improves post-surgical bone recovery or interferes with the natural bone remodeling process following PTX. Additionally, it will provide insight into the cardiovascular and renal effects of bisphosphonate therapy in PHPT patients. Findings may help guide treatment strategies for optimizing long-term skeletal and systemic health in this patient population.

Conditions

Primary Hyperparathyroidism

Keywords

zoledronate; parathyroidectomy; placebo

Outcome Measures

Primary Outcomes (1)

• Effects of ZOL vs. placebo at time of parathyroidectomy based on change in aBMD at lumbar spine meased at baseline compared to one year after PTX.

  aBMD (g/cm\^3) will be measured by DXA-scans at baseline and one year after PTX.

  12 months (one year)

Secondary Outcomes (11)

• Effects of ZOL at aBMD at distal forearm

  12 months (one year)

• Effects of ZOL at aBMD at femoral neck

  12 months (one year)

• Effects of ZOL at aBMD at total hip

  12 months (one year)

• Effects on microarchitecture measured by high-resolution peripheral computed tomography (HRpQCT).

  12 months

• Effects on biochemical bone turnover markers (BTM).

  12 months

Study Arms (2)

Zoledronic acid

ACTIVE COMPARATOR

Patients referred to Aarhus University Hospital (AUH) for PTX due to PHPT will be included prospectively. We aim to include 140 patients with PHPT - 70 patients in each group. Patients will be enrolled consecutively until the required number of participants have been achieved. Enrolled participants will be randomized to intervention (active medicine) or placebo group and receive either zoledronate or placebo (saline water) 2-4 weeks prior to PTX.

Drug: Zoledronic acid 4 mg

Placebo

PLACEBO COMPARATOR

Patients referred to Aarhus University Hospital (AUH) for PTX due to PHPT will be included prospectively. We aim to include 140 patients with PHPT - 70 patients in each group. Patients will be enrolled consecutively until the required number of participants have been achieved. Enrolled participants will be randomized to intervention (active medicine) or placebo group and receive either zoledronate or placebo (saline water) 2-4 weeks prior to PTX.

Drug: Natriumklorid 9 mg/ml, Fresenius Kabi

Interventions

Zoledronic acid 4 mg DRUG

Product name/EU MP number: Zoledronic Acid Oresund Pharma 4 mg/100 ml infusionsvätska, lösning/PRD8924813 (Test) Substance (name/ code): ZOLEDRONIC ACID/SUB00176MIG Strength: Zoledronic Acid 0.04mg Pharmaceutical form: SOLUTION FOR INFUSION Route of administration: INFUSIÓN INTRAVENOSA Marketing authorisation status (MA number, MS where authorised etc): 52486 / SE Modified in relation to MA: No Max Dosage: mg milligram(s) Duration of use: Week

Also known as: ZOL, Zoledronate, Zoledronate acid

Zoledronic acid

Natriumklorid 9 mg/ml, Fresenius Kabi DRUG

Product name/EU MP number: Natriumklorid "Baxter" ClearFlex 9 mg/ml,infusionsvæske, opløsning/PRD456031 (Placebo) Substance (name/ code): SODIUM CHLORIDE/SUB12581MIG Strength: Sodium Chloride 0.9g / 100mL Pharmaceutical form: SOLUTION FOR INFUSION Route of administration: INFUSIÓN INTRAVENOSA Marketing authorisation status (MA number, MS where authorised etc): 32466 / DK Modified in relation to MA: No Max Dosage: ml millilitre(s) Duration of use: Week

Also known as: saline water

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal females or males \> 50 years
• A diagnosis of hyperparathyroid hypercalcemia due to sporadic PHPT referred to PTX
• aBMD T-score ≤ -1 at total hip, femoral neck, or lumbar spine
• hydroxyvitamin D ≥ 50 nmol/l prior to randomization
• Willingness to undergo PTX

You may not qualify if:

• Known or suspected familial ethology (e.g., MEN1 or 2)
• Estimated glomerular filtration rate \< 35 ml/min
• Known allergy to bisphosphonates
• Planned or recent (within the last 3 months) major dental procedures (e.g., jaw surgery or tooth extraction)
• Chronic or acute disorders (e.g., rheumatoid arthritis, inflammatory bowel disease, cancer) or prior medications (e.g., lithium, glucocorticoids within the last year, antiresorptive or bone anabolic treatment within the last 3 years) known to affect bone metabolism.

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Aarhus University Hospital

Aarhus N, Central Region of Denmark, 8200, Denmark

RECRUITING

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MeSH Terms

Conditions

Hyperparathyroidism, Primary

Interventions

Zoledronic Acid; Saline Waters

Condition Hierarchy (Ancestors)

Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Environment; Ecological and Environmental Phenomena; Biological Phenomena

Study Officials

• Lars Rejnmark, Professor

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne Louise Vandsø Svenningsen, MD

CONTACT

+45 60183895; ansvnn@rm.dk

Henriette Ejlsmark Svensson, MD, PhD

CONTACT

henrkn@rm.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2025
• First Posted: March 5, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: March 25, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Start date is time of publication. End date is 5 years after publication.
• Access Criteria: By contacting the leading author of the publication in order to make a data sharing agreement, which should be signed. Proposal for agreement must contain planned analyses. Statistical analyses have to be approved by independent review before published. Data sharing agreement needs to be approved by the Technology Transfer Office (TTO), Aarhus University Hospital, Denmark.

Locations

DK (1)