Cardiovascular Effects of Parathyroid Hormone Analogues in Chronic Hypoparathyroidism
PaTH CV
Effect of Long-acting PTH Analogues on Markers of Subclinical Arterial and Myocardial Injury in Chronic Hypoparathyroidism..
1 other identifier
observational
210
1 country
2
Brief Summary
The goal of this study is to evaluate cardiovascular effects of long-acting parathyroid hormone (PTH) analogues in adults with chronic hypoparathyroidism. The main questions it aims to answer are:
- Do patients with hypoparathyroidism have increased arterial stiffness and markers of subclinical cardiovascular injury compared to healthy individuals?
- Does treatment with a long-acting PTH analogue improve vascular and cardiac function over time compared to conventional therapy? This is a multi-center study with two parts: a cross-sectional comparison and a 12-month prospective follow-up. Adults with chronic hypoparathyroidism and matched healthy controls will undergo clinical evaluation, vascular measurements, cardiac imaging, and blood tests. In the prospective part, patients that just started long-acting PTH analogue therapy based on their treating physicians choice will be followed for 12 months, with repeat assessments at baseline, 3 months, and 12 months to evaluate changes in cardiovascular markers.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Apr 2026
Typical duration for all trials
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2026
CompletedFirst Submitted
Initial submission to the registry
April 19, 2026
CompletedFirst Posted
Study publicly available on registry
July 16, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2028
July 16, 2026
July 1, 2026
1 year
April 19, 2026
July 15, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Differences between PTH-treated group, disease control group, and healthy controls in carotid-femoral pulse wave velocity (cfPWV)
Differences in carotid-femoral pulse wave velocity (cfPWV) between patients with hypoparathyroidism receiving conventional therapy, patients treated with long-acting PTH analogue (palopegteriparatide/TransCon PTH), and healthy controls. Two different pulse waves are obtained at the same time transcutaneously with the patient in a supine position at 2 sites, at the right common carotid artery and the right femoral artery (i.e. 'carotid-femoral' PWV) by using pressure-sensitive transducers. The distance traveled by the pulse wave is measured over the body surface and calculated by subtracting the carotid (sternal notch from the carotid)-femoral distance as distance/time (m/s) .
For the cross-sectional (baseline comparison):At baseline For the prospective (interventional) endpoint: From baseline, to 3 and 12 months
Secondary Outcomes (22)
Differences between PTH-treated group, disease control group, and healthy controls in central blood pressure
For the cross-sectional (baseline comparison):At baseline For the prospective (interventional) endpoint: From baseline, to 3 and 12 months
Differences between PTH-treated group, disease control group, and healthy controls in peripheral blood pressure
For the cross-sectional (baseline comparison):At baseline For the prospective (interventional) endpoint: From baseline, to 3 and 12 months
Differences between PTH-treated group, disease control group, and healthy controls in carotid intima-media thickness (IMT)
For the cross-sectional (baseline comparison):At baseline For the prospective (interventional) endpoint: From baseline to 12 months
Differences between PTH-treated group, disease control group, and healthy controls in sublingual microcirculation parameters (vascular density)
For the cross-sectional (baseline comparison):At baseline For the prospective (interventional) endpoint: From baseline to 12 months
Differences between PTH-treated group, disease control group, and healthy controls in fundoscopic vascular findings.
For the cross-sectional (baseline comparison):At baseline For the prospective (interventional) endpoint: From baseline to 12 months
- +17 more secondary outcomes
Study Arms (4)
Patients with chronic hypoparathyroidism under conventional treatment (disease control)
20-30 Hypo-PT patients aged ≥18 on conventional HypoPT therapy with any dose of activated vitamin D and calcium and native vitamin D supplements for at least 12 months
Patients with chronic hypoparathyroidism under treatment with palopegteriparatide
40-50 Hypo-PT patients aged ≥18 treated with Palopegteriparatide (TransCon PTH) for at least 12 months
Healthy controls
Healthy controls: 170 Healthy controls matched with group 1 and group 2 for age, sex, CVD presence, propensity score, DM2, renal function, BMI and SBP, retrospectively recruited from the Athens Angiometabolic Cohort
Patients with chronic hypoparathyroidism switching from conventional therapy to palopegteriparatide
20 patients starting treatment with palopegteriparatide, previously on conventional treatment
Interventions
Participants will undergo a baseline echocardiographic examination. Standard protocol will be used and standard measurements from 2-D and Doppler echocardiography will be made. LV end-diastolic and end-systolic volumes, as well as ejection fraction, will be derived from the apical 4- and 2-chamber views using the biplane Simpson's rule. Left ventricular mass will be calculated according to Devereux's formula. Doppler examination will include interrogation of mitral inflow, and early (E) and late (A) peak diastolic velocities and deceleration time will be measured. Tissue Doppler analysis will include pulse wave interrogation of the medial and lateral mitral annulus, peak diastolic early E΄ annular velocities will be obtained and the mean value and E/E' will be calculated. In addition, Speckle-tracking analysis will be applied to estimate LV rotational mechanics, and longitudinal strain parameters. Parasternal short-axis views at the level of the mitral valve and apex, and standard apic
Carotid-femoral pulse wave velocity (c-f PWV) is an established index of aortic stiffness and an independent predictor of worse cardiovascular prognosisIt is considered as the gold standard for assessing aortic stiffness non-invasively and is calculated from measurements of pulse transit time and the distance travelled between 2 recording sites with a validated non-invasive device (Complior, Artech Medical, France). Two different pulse waves are obtained at the same time transcutaneously with the patient in a supine position at 2 sites, at the right common carotid artery and the right femoral artery (i.e. 'carotid-femoral' PWV) by using pressure-sensitive transducers.
Non-invasive estimation of aortic pressure waveforms and reflected waves by pulse wave analysis (PWA) will be performed in the Angiology laboratory by the SphygmoCor System (AtCor Medical Pty Ltd, Sydney, Australia). The radial artery is gently and steadily compressed against the underlying bone, thus flattening it and equalizing circumferential pressures, allowing radial pressure waves to be recorded by a high fidelity micromanometer placed on the tip of a hand - held tonometer the size of a pen (Millar). Optimal recording is obtained if the wrist is bent outward and supported by using a small cushion or the operator's hand. The following indices are measured: 1. augmentation index (AI, percentage) normalized for the heart rate of 75 bpm, expressed as a percentage of the aortic pulse pressure, 2. central systolic and diastolic pressures (cBP), 3. time to the beginning of the reflected wave (in milliseconds) and 4. blood pressure amplification calculated as the ratio of peripheral
B-mode ultrasound examination will also be performed, using a 14.0 MHz multi-frequency linear array probe attached to a high-resolution ultrasound machine (Vivid 7 Pro, GE Healthcare, USA). All scans are going to be performed by the same operator. Carotid intima-media thickness (ccIMT) will be measured at the distal 1.0 cm of the common carotid proximal to the bifurcation as previously described (23) . In each segment 3 measurements of the maximal IMT in the far wall will be averaged, after excluding plaque thickness. The average of the maximal IMT will be used in the analyses. Femoral IMT (fIMT) will be measured on each side, scanning a 1cm-long arterial segment proximal to the femoral bifurcation, defined as the common femoral artery segment and the average value of IMT of the far wall will be estimated. A cutoff value of \>0.9 mm for mean ccIMT or fIMT will be considered increased. Plaques to carotid and femoral arteries are defined as a focal structure that protrudes into the arteri
The measurement procedure and the calculation of the sublingual microvascular parameters is performed as follows: the probe of a hand-held side-stream darkfield (SDF) videomicroscope (CapiScope HVCS, KK Technology, Honiton, UK) is placed on the sublingual mucosa of the subject, to obtain video recordings of the sublingual microvasculature. Subsequently, an analysis software (the GlycoCheck Measurement System Software Version 5.3.3) selects and analyses SDF images that are of sufficient quality (adequate focus, adequate contrast and limited movement) and automatically calculates the sublingual microcirculation parameters, such as vascular density (VD), red blood cell filling (RBCF), and perfused boundary region (PBR).
The primary non-invasive test for the diagnosis of lower extremity artery disease (LEAD) is the ABI. A cut-off value of \<0.9 will be used for the diagnosis of LEAD and as predictive index of atherosclerosis, associated with increased risk of cardiovascular morbidity and mortality. Also, a cut-off value of \>1.40 will be used as an index of stiffened arteries, also associated with increased mortality. For its measurement, a 10-12 cm sphygmomanometer cuff will be placed just above the ankle and a (handheld) Doppler instrument (5-10 MHz) will measure the pressure of the posterior and anterior tibial arteries of each foot. The highest ankle systolic pressure will be divided by the highest brachial systolic pressure, resulting in an ABI per leg.
A set of colour and black-and-white fundus images photograph per eye will be taken by well-trained ophthalmic photographers: macula-centered images using the handheld Optomed Aurora fundus cameras without pupil dilation. The images obtained with the handheld fundus camera had a field of view of 50° and 5 mega-pixel resolution
In order to calculate local shear stress in brachial and carotid artery, measurements of mean flow velocity in the lumen of these arteries will be needed. These measurements will be obtained, while performing carotid ultrasonography and FMD in brachial artery, as previously described. In detail, the form to calculate shear stress is: shear stress (in dyn/cm2 ) = 8×μ× mean flow velocity/resting diameter, where μ is the viscosity of blood which was assumed to be 0.035 dyne s/cm2
The peripheral and aortic office blood pressure will be assessed using specialized equipment (certified blood pressure monitor). 24-hour Ambulatory Blood pressure monitoring for measurement of 24 hour peripheral and aortic
Fasting venous blood samples will be collected for evaluation of myocardial biomarkers (hs-troponin I, NT-proBNP). Additional samples will be obtained for isolation of PBMCs.
Fasting venous blood samples will be collected for evaluation of calcium metabolism (PTH, calcium, albumin, magnesium, phosphate, 25-hydroxyvitamin D) .
Eligibility Criteria
Adults (≥18y) with chronic HypoPT (≥12 months) currently treated with conventional therapy or palopegteriparatide for more than one year and comparable healthy individuals, matched to patients based on key characteristics such as age, sex, and cardiovascular risk factors
You may qualify if:
- \- Cross sectional arm: Baseline State: Adults (≥18y) with chronic HypoPT (≥12 months) currently treated with conventional therapy or palopegteriparatide for more than one year
- Prospective Follow-up: Adults (≥18y) with chronic HypoPT (≥12 months) currently treated with conventional therapy and about to start treatment with palopegteriparatide willing to undergo baseline measurements (prior to the first dose) and repeat measurements at 3 and 12 months.
You may not qualify if:
- Renal Function: CKD Stage 3 or higher (eGFR \< 60 mL/min/1.73 m²)
- Uncontrolled Risk Factors:
- SBP \> 180/100 mmHg
- Uncontrolled endocrine diseases (e.g., hyper- or hypothyroidism, diabetes mellitus type 2 with HbA1c\>7.5%).
- Bone Health: Any metabolic bone disease other than hypoparathyroidism (excluding osteoporosis)
- Documented Atrial Fibrillation (ECG)
- Contraindication to long acting PTH analogue as per product labeling
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National and Kapodistrian University of Athenslead
- 251 Hellenic Air Force & VA General Hospitalcollaborator
- Alexandra Hospital, Athens, Greececollaborator
- G.Gennimatas General Hospitalcollaborator
- Laikο General Hospital, Athenscollaborator
- Korgialenio-Benakio Red Cross Hospitalcollaborator
- AHEPA University Hospitalcollaborator
- 424 General Military Hospitalcollaborator
- Hippocration General Hospitalcollaborator
- KAT Hospital of Athenscollaborator
- Evaggelismos Hospital, Greececollaborator
Study Sites (2)
Alexandra General Hospital of Athens
Athens, 11527, Greece
Medical School, National and Kapodistrian University of Athens, LAIKO General Hospital of Athens
Athens, 11527, Greece
Biospecimen
Serum and plasma samples will be retained
MeSH Terms
Conditions
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Kimon Stamatelopoulos, MD
Medical School, National and Kapodistrian University of Athens
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Senior Endocrinology Consultant
Study Record Dates
First Submitted
April 19, 2026
First Posted
July 16, 2026
Study Start
April 1, 2026
Primary Completion (Estimated)
April 1, 2027
Study Completion (Estimated)
December 31, 2028
Last Updated
July 16, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- 31/12/2027 for 5 years
Only IPD used in the results publication