Effect of Long-acting PTH Analogues on Markers of Subclinical Arterial and Myocardial Injury in Chronic Hypoparathyroidism..
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 210
- 试验地点
- 2
- 主要终点
- Differences between PTH-treated group, disease control group, and healthy controls in carotid-femoral pulse wave velocity (cfPWV)
研究概览
简要总结
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.
详细描述
The goal of this study is to better understand how chronic hypoparathyroidism affects heart and blood vessel health, and whether treatment with a long-acting parathyroid hormone (PTH) analogue can improve cardiovascular function. Hypoparathyroidism is a rare condition in which the body does not produce enough PTH, leading to low calcium levels and possible long-term complications, including an increased risk of cardiovascular disease.
This study aims to answer the following main questions:
Do people with chronic hypoparathyroidism have early (subclinical) signs of damage to the heart and blood vessels compared to people without the condition? Does treatment with a long-acting PTH analogue improve vascular health and reduce early markers of cardiovascular disease over time?
The study includes two parts. In the first part, researchers will compare adults with hypoparathyroidism-either receiving standard treatment (calcium and vitamin D) or long-acting PTH therapy-with healthy individuals of similar age and health characteristics. Participants that will undergo the non-invasive tests to assess blood vessel stiffness, blood pressure, microcirculation, and heart function, along with blood tests to measure calcium balance and cardiovascular biomarkers, as part of routine clinical practice will be eligible for the study.
In the second part, participants with hypoparathyroidism who are starting treatment with a long-acting PTH analogue will be followed for 12 months. They will be evaluated at the beginning of the study, at 3 months and again at 12 months. Researchers will track changes in blood vessel function, heart performance, and biochemical markers to determine whether restoring normal PTH levels improves cardiovascular health.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •- 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.
排除标准
- •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
结局指标
主要结局
Differences between PTH-treated group, disease control group, and healthy controls in carotid-femoral pulse wave velocity (cfPWV)
时间窗: For the cross-sectional (baseline comparison):At baseline For the prospective (interventional) endpoint: From baseline, to 3 and 12 months
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) .
次要结局
- 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)
- Differences between PTH-treated group, disease control group, and healthy controls in local shear stress in brachial artery.(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 N-terminal pro-B-type natriuretic peptide (NT-proBNP)(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 high-sensitivity cardiac troponin (hs-cTn).(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 serum phosphate(For the cross-sectional arm (baseline comparison): At baseline. For the prospective (interventional) endpoint: At baseline and 12 months.)
- Differences between PTH-treated group, disease control group, and healthy controls in albumin-adjusted serum calcium(For the cross-sectional arm (baseline comparison): At baseline. For the prospective (interventional) endpoint: At baseline and 12 months.)
- Differences between PTH-treated group, disease control group, and healthy controls in Time to Reflected Wave(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 serum magnesium(For the cross-sectional arm (baseline comparison): At baseline. For the prospective (interventional) endpoint: At baseline and 12 months.)
- Differences between PTH-treated group, disease control group, and healthy controls in serum intact parathyroid hormone (PTH)(For the cross-sectional arm (baseline comparison): At baseline. For the prospective (interventional) endpoint: At baseline and 12 months.)
- Differences between PTH-treated group, disease control group, and healthy controls in serum 25-hydroxyvitamin D(For the cross-sectional arm (baseline comparison): At baseline. For the prospective (interventional) endpoint: At baseline and 12 months.)
- Differences between PTH-treated group, disease control group, and healthy controls in left ventricular global longitudinal strain (GLS)(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 Blood Pressure Amplification(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 left ventricular ejection fraction (LVEF)(For the cross-sectional arm (baseline comparison): At baseline. For the prospective (interventional) endpoint: At baseline, 12 months.)
- Differences between PTH-treated group, disease control group, and healthy controls in left ventricular diastolic function (E/E')(For the cross-sectional arm (baseline comparison): At baseline. For the prospective (interventional) endpoint: At baseline, 12 months.)
- Differences between PTH-treated group, disease control group, and healthy controls in Augmentation Index (AIx)(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 Central Systolic Blood Pressure(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 Central Diastolic Blood Pressure(For the cross-sectional (baseline comparison):At baseline For the prospective (interventional) endpoint: From baseline to 12 months)
- Differences in the Ankle-brachial index (ABI), between PTH-treated group, disease control group, and healthy controls(For the cross-sectional (baseline comparison):At baseline For the prospective (interventional) endpoint: From baseline, to 3 and 12 months)
研究者
Maria Yavropoulou
Senior Endocrinology Consultant
National and Kapodistrian University of Athens