Hyperparathyroidism, PrimaryPARABONENCT05556499
The Bone-parathyroid Crosstalk in Primary Hyperparathyroidism
An observational study of Hyperparathyroidism, Primary and Osteoporosis, run by I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio at 1 site in Italy.
Trial summary
The PARABONE study aims to investigate the interaction between bone and parathyroid glands in patients with primary hyperparathyroidism (HPT). The study consists of a clinical part aimed at evaluating a series of circulating molecules of bone derivation (osteocalcin, molecules of the WNT pathway, RANKL… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyperparathyroidism, Primary, Osteoporosis, Parathyroid Neoplasms
- What is being tested?
- Biomarker assays
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- Oct 2022to 24 Jun 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Male and female patients aged ≥ 18 years with a diagnosis of HPT according to the most recent guidelines will be enrolled in the study [Marcocci et al. 2015] with and without indication for surgical treatment. Serum and plasma samples will be collected from all patients with HPT and parathyroid tumor samples from patients diagnosed with HPT with indication for surgical treatment according to the guidelines [Bilezikian et al. 2014, Marcocci et al. 2015].
Who may be able to join
- diagnosis of primary hyperparathyroidism according to the most recent guidelines [Marcocci et al. 2015];
- adult patients (age ≥ 18 years);
- signature of the informed consent.
- diagnosis of primary hyperparathyroidism with indication of surgical removal of the parathyroid tumor according to the most recent guidelines [Marcocci et al. 2015];
- adult patients (age ≥18 years);
- signature of the informed consent.
Who cannot join
- Criteria for exclusion from the study are:
- age <18 years
- diagnosis of hyperparathyroidism secondary to chronic renal failure or to vitamin D or calcium deficiency;
- pregnancy or breastfeeding (self-declaration)
- lack of informed consent
Trial locations and contacts
1 site in 1 country.
Italy1 site
IRCCS Istituto Ortopedico Galeazzi
Milan, 20157
Sabrina Corbetta, PhD, MD, sabrina.corbetta@unimi.it
Sara Zacchetti, sara.zacchetti@grupposandonato.it
About this study
Official title: Interactions Between Bone and Parathyroid Tumors in Patiens With Primary Hyperparathyroidism (The PARABONE Study)
The PARABONE study aims to investigate the interaction between bone and parathyroid glands in patients with primary hyperparathyroidism (HPT). The study consists of a clinical part aimed at evaluating a series of circulating molecules of bone derivation (osteocalcin, molecules of the WNT pathway, RANKL, osteoprotegerin, Scelrostin, FGF23) in patients with HPT. In particular, the study has as its primary objective to identify the correlation between circulating levels of PTH and levels of GlaOC and GluOC in patients with HPT.
Read the detailed description
The parathyroid glands are responsible for controlling mineral homeostasis in order to keep circulating calcium levels constant by acting on the target organs, where they induce mobilization of calcium from the bone matrix, and they promote the reabsorption of calcium from the ultra-filtrate at renal level. In turn, kidney and bone can affect the functioning of the parathyroid glands, for example through the action of FGF23 secreted by osteocytes. Primary hyperparathyroidism (HPT) is an endocrine disorder that causes bone demineralization, osteoporosis and fragility fractures, representing a frequent cause of secondary osteoporosis. It is prevalent in postmenopausal women, where it is the third most frequent endocrine pathology after diabetes and thyroid disease. In postmenopausal women, the pattern of demineralization induced by estrogen deficiency may overlap with that secondary to HPT. HPT is sustained by tumors of the parathyroid glands, mainly of a benign nature, associated with inappropriate secretion of parathyroid hormone (PTH), which causes hypercalcemia and bone, kidney and cardiovascular complications. It is known that persistent secondary hyperparathyroidism, such as that induced by idiopathic hypercalciuria or malabsorption related to vitamin D deficiency, can stimulate the proliferation of parathyroid cells and the autonomous hypersecretion of PTH. Therefore, it is conceivable that also alterations in bone metabolism, such as a persistently increased release of osteocalcin (OC), can promote the proliferation of parathyroid cells and/or hypersecretion of PTH. Interestingly, the circulating levels of carboxylated and decarboxylated osteocalcin (GlaOC and GluOC) were found to be increased in patients with HPT. Furthermore, elevated circulating OC levels appear to be predictive of multiglandular disease in HPT patients. Osteoblasts are one of the main targets of PTH action and release biologically active molecules with paracrine and endocrine action, including osteocalcin (GlaOC and GluOC), the molecules of the intracellular signaling pathway WNT and the RANK ligand (Receptor Activator for Nuclear Factor-κB, RANKL). Therefore, it is conceivable that these biologically active molecules released by osteoblasts can induce biological effects of modulating the functioning of parathyroid cells, in a sort of bone-parathyroid regulatory loop, and thus modulate the presentation phenotype and clinical severity of HPT. RANKL and sclerostin are the specific targets of monoclonal anti-osteoporotic treatments currently available; therefore understanding their potential effect on parathyroid function in HPT can provide the rationale for new therapeutic approaches for patients with HPT. The expected results will allow to improve the diagnosis of HPT, in particular to better define the extent of bone compromise related to it, evaluating circulating bone markers so far not explored. The investigators therefore intend to clarify the effect of hormones released by osteoblasts on parathyroid function, taking into account that these hormones are the target of currently available anti-osteoporotic therapies. The translational study will therefore allow to identify new pathogenetic mechanisms in parathyroid tumorigenesis promoted by endocrine factors released by osteoblasts, which will be able to provide potential targets for targeted medical treatments.
- Being tested
- Biomarker assays
- Medical subject headings
- Hyperparathyroidism, Primary, Osteoporosis, Parathyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biomarker assaysDiagnostic test
Circulating bone biomarkers assays
| Study group | Role | What they receive |
|---|---|---|
| HPT patients | Patients with primary hyperparathyroidism at diagnosis (HPT) treated with parathyroidectomy (HPT-PTX) Receives: Diagnostic Test: Biomarker assays |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between circulating GlaOC and PTH levels in HPT patients
The study aims to investigate the effect of the circulating carboxylated osteocalcin isoform (GlaOC) on the biochemical phenotype in patients with HPT
Measured: 42 months
Secondary outcomes (1)
Effects of bone derived molecules on the biochemical phenotypes and parathyroid tumor cells function in HPT patients
Correlation between the clinical and biochemical characteristics of HPT patients with circulating levels of the two isoforms of osteocalcin and other hormones produced by bone (molecules of the WNT pathway, RANKL, Osteoprotegerin, Sclerostin, FGF23, IL-17). Analysis of the expression of circulating lncRNAs and microRNAs in patients with HPT in relation to the osteo-metabolic state. Analysis of the expression pattern of genes involved in parathyroid tumorigenesis and in bone-parathyroid crosstalk, lncRNAs and microRNAs in parathyroid cancer cells in order to further define the heterogeneity of the adenoma histotype in relation to the osteo-metabolic state.Define the biological effect of the hormones released from bone on parathyroid cancer cells. Define the biological effect and the interaction with the parathyroid function of the hormones released from bone in HEK293A models transfected with the CASR and / or transfected with the receptors of the molecules released by bone.
Measured: 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2022
- Study startOct 2022 (estimated)
- Primary completion24 May 2026 (estimated)
- Study completion24 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Hyperparathyroidism, PrimaryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sabrina Corbetta, PhD, MD, Principal investigator, IRCCS Istituto Ortopedico Galeazzi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05556499
- Sponsor's protocol ID
- PARABONE (L4126)
- Acronym
- PARABONE
- Status last verified
- Sep 2022
- First submitted
- 23 Sep 2022
- Last updated
- 30 Sep 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gianotti L, Piovesan A, Croce CG, Pellegrino M, Baffoni C, Cesario F, Visconti G, Borretta G, Tassone F. Interplay between serum osteocalcin and insulin sensitivity in primary hyperparathyroidism. Calcif Tissue Int. 2011 Mar;88(3):231-7. doi: 10.1007/s00223-010-9453-1. Epub 2011 Jan 5.
PubMed 21207016Marcocci C, Brandi ML, Scillitani A, Corbetta S, Faggiano A, Gianotti L, Migliaccio S, Minisola S. Italian Society of Endocrinology Consensus Statement: definition, evaluation and management of patients with mild primary hyperparathyroidism. J Endocrinol Invest. 2015 May;38(5):577-93. doi: 10.1007/s40618-015-0261-3. Epub 2015 Mar 28. No abstract available.
PubMed 25820553Maser RE, Lenhard MJ, Pohlig RT, Balagopal PB, Abdel-Misih R. Effect of parathyroidectomy on osteopontin and undercarboxylated osteocalcin in patients with primary hyperparathyroidism. Endocr Res. 2018 Feb;43(1):21-28. doi: 10.1080/07435800.2017.1369432. Epub 2017 Sep 22.
PubMed 28937873Mendonca ML, Batista SL, Nogueira-Barbosa MH, Salmon CE, Paula FJ. Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance. Clinics (Sao Paulo). 2016 Aug;71(8):464-9. doi: 10.6061/clinics/2016(08)09.
PubMed 27626477Thier M, Daudi S, Bergenfelz A, Almquist M. Predictors of multiglandular disease in primary hyperparathyroidism. Langenbecks Arch Surg. 2018 Feb;403(1):103-109. doi: 10.1007/s00423-017-1647-9. Epub 2018 Jan 2.
PubMed 29294178Parveen B, Parveen A, Vohora D. Biomarkers of Osteoporosis: An Update. Endocr Metab Immune Disord Drug Targets. 2019;19(7):895-912. doi: 10.2174/1871530319666190204165207.
PubMed 30727928Bilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C, Potts JT Jr. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014 Oct;99(10):3561-9. doi: 10.1210/jc.2014-1413. Epub 2014 Aug 27.
PubMed 25162665
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interactions Between Bone and Parathyroid Tumors in Patiens With Primary Hyperparathyroidism (The PARABONE Study)
- ClinicalTrials.gov ID
- NCT05556499
- Acronym / sponsor ID
- PARABONE / PARABONE (L4126)
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- I.R.C.C.S Ospedale Galeazzi-Sant'AmbrogioUniversity, hospital or other
- Study start
- Oct 2022 (estimated)
- Primary completion
- 24 May 2026 (estimated)
- Study completion
- 24 Jun 2026 (estimated)
- First posted
- 27 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The PARABONE study aims to investigate the interaction between bone and parathyroid glands in patients with primary hyperparathyroidism (HPT). The study consists of a clinical part aimed at evaluating a series of circulating molecules of bone derivation (osteocalcin, molecules of the WNT pathway, RANKL, osteoprotegerin, Scelrostin, FGF23) in patients with HPT. In particular, the study has as its primary objective to identify the correlation between circulating levels of PTH and levels of GlaOC and GluOC in patients with HPT.
Detailed description
The parathyroid glands are responsible for controlling mineral homeostasis in order to keep circulating calcium levels constant by acting on the target organs, where they induce mobilization of calcium from the bone matrix, and they promote the reabsorption of calcium from the ultra-filtrate at renal level. In turn, kidney and bone can affect the functioning of the parathyroid glands, for example through the action of FGF23 secreted by osteocytes. Primary hyperparathyroidism (HPT) is an endocrine disorder that causes bone demineralization, osteoporosis and fragility fractures, representing a frequent cause of secondary osteoporosis. It is prevalent in postmenopausal women, where it is the third most frequent endocrine pathology after diabetes and thyroid disease. In postmenopausal women, the pattern of demineralization induced by estrogen deficiency may overlap with that secondary to HPT. HPT is sustained by tumors of the parathyroid glands, mainly of a benign nature, associated with inappropriate secretion of parathyroid hormone (PTH), which causes hypercalcemia and bone, kidney and cardiovascular complications. It is known that persistent secondary hyperparathyroidism, such as that induced by idiopathic hypercalciuria or malabsorption related to vitamin D deficiency, can stimulate the proliferation of parathyroid cells and the autonomous hypersecretion of PTH. Therefore, it is conceivable that also alterations in bone metabolism, such as a persistently increased release of osteocalcin (OC), can promote the proliferation of parathyroid cells and/or hypersecretion of PTH. Interestingly, the circulating levels of carboxylated and decarboxylated osteocalcin (GlaOC and GluOC) were found to be increased in patients with HPT. Furthermore, elevated circulating OC levels appear to be predictive of multiglandular disease in HPT patients. Osteoblasts are one of the main targets of PTH action and release biologically active molecules with paracrine and endocrine action, including osteocalcin (GlaOC and GluOC), the molecules of the intracellular signaling pathway WNT and the RANK ligand (Receptor Activator for Nuclear Factor-κB, RANKL). Therefore, it is conceivable that these biologically active molecules released by osteoblasts can induce biological effects of modulating the functioning of parathyroid cells, in a sort of bone-parathyroid regulatory loop, and thus modulate the presentation phenotype and clinical severity of HPT. RANKL and sclerostin are the specific targets of monoclonal anti-osteoporotic treatments currently available; therefore understanding their potential effect on parathyroid function in HPT can provide the rationale for new therapeutic approaches for patients with HPT. The expected results will allow to improve the diagnosis of HPT, in particular to better define the extent of bone compromise related to it, evaluating circulating bone markers so far not explored. The investigators therefore intend to clarify the effect of hormones released by osteoblasts on parathyroid function, taking into account that these hormones are the target of currently available anti-osteoporotic therapies. The translational study will therefore allow to identify new pathogenetic mechanisms in parathyroid tumorigenesis promoted by endocrine factors released by osteoblasts, which will be able to provide potential targets for targeted medical treatments.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HPT patients | – | Diagnostic Test: Biomarker assaysPatients with primary hyperparathyroidism at diagnosis (HPT) treated with parathyroidectomy (HPT-PTX) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Male and female patients aged ≥ 18 years with a diagnosis of HPT according to the most recent guidelines will be enrolled in the study [Marcocci et al. 2015] with and without indication for surgical treatment. Serum and plasma samples will be collected from all patients with HPT and parathyroid tumor samples from patients diagnosed with HPT with indication for surgical treatment according to the guidelines [Bilezikian et al. 2014, Marcocci et al. 2015].
Key inclusion criteria (6 listed)
- diagnosis of primary hyperparathyroidism according to the most recent guidelines [Marcocci et al. 2015];
- adult patients (age ≥ 18 years);
- signature of the informed consent.
- diagnosis of primary hyperparathyroidism with indication of surgical removal of the parathyroid tumor according to the most recent guidelines [Marcocci et al. 2015];
- adult patients (age ≥18 years);
Key exclusion criteria (5 listed)
- Criteria for exclusion from the study are:
- age <18 years
- diagnosis of hyperparathyroidism secondary to chronic renal failure or to vitamin D or calcium deficiency;
- pregnancy or breastfeeding (self-declaration)
- lack of informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biomarker assaysCirculating bone biomarkers assays | Diagnostic test | HPT patients |
Primary outcome
Correlation between circulating GlaOC and PTH levels in HPT patients
Time frame: 42 months
The study aims to investigate the effect of the circulating carboxylated osteocalcin isoform (GlaOC) on the biochemical phenotype in patients with HPT
1 secondary outcome
Effects of bone derived molecules on the biochemical phenotypes and parathyroid tumor cells function in HPT patients
Time frame: 42 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2022.
- Results publication: PubMed 21207016Gianotti L, Piovesan A, Croce CG, Pellegrino M, Baffoni C, Cesario F, Visconti G, Borretta G, Tassone F. Interplay between serum osteocalcin and insulin sensitivity in primary hyperparathyroidism. Calcif Tissue Int. 2011 Mar;88(3):231-7. doi: 10.1007/s00223-010-9453-1. Epub 2011 Jan 5.
- Results publication: PubMed 25820553Marcocci C, Brandi ML, Scillitani A, Corbetta S, Faggiano A, Gianotti L, Migliaccio S, Minisola S. Italian Society of Endocrinology Consensus Statement: definition, evaluation and management of patients with mild primary hyperparathyroidism. J Endocrinol Invest. 2015 May;38(5):577-93. doi: 10.1007/s40618-015-0261-3. Epub 2015 Mar 28. No abstract available.
- Results publication: PubMed 28937873Maser RE, Lenhard MJ, Pohlig RT, Balagopal PB, Abdel-Misih R. Effect of parathyroidectomy on osteopontin and undercarboxylated osteocalcin in patients with primary hyperparathyroidism. Endocr Res. 2018 Feb;43(1):21-28. doi: 10.1080/07435800.2017.1369432. Epub 2017 Sep 22.
- Results publication: PubMed 27626477Mendonca ML, Batista SL, Nogueira-Barbosa MH, Salmon CE, Paula FJ. Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance. Clinics (Sao Paulo). 2016 Aug;71(8):464-9. doi: 10.6061/clinics/2016(08)09.
- Results publication: PubMed 29294178Thier M, Daudi S, Bergenfelz A, Almquist M. Predictors of multiglandular disease in primary hyperparathyroidism. Langenbecks Arch Surg. 2018 Feb;403(1):103-109. doi: 10.1007/s00423-017-1647-9. Epub 2018 Jan 2.
- Results publication: PubMed 30727928Parveen B, Parveen A, Vohora D. Biomarkers of Osteoporosis: An Update. Endocr Metab Immune Disord Drug Targets. 2019;19(7):895-912. doi: 10.2174/1871530319666190204165207.
- Results publication: PubMed 25162665Bilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C, Potts JT Jr. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014 Oct;99(10):3561-9. doi: 10.1210/jc.2014-1413. Epub 2014 Aug 27.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sabrina Corbetta, PhD, MD principal investigator
IRCCS Istituto Ortopedico Galeazzi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hyperparathyroidism, Primary and Osteoporosis, run by I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sabrina Corbetta, PhD, MD (+39 02 83506781, sabrina.corbetta@unimi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation between circulating GlaOC and PTH levels in HPT patients (time frame: 42 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05556499, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2022.