Effects of aLdosterone Inhibition by baXdrostat on Molecular Imaging of cytoReduction in Primary Aldosteronism and Hypertension
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Change in total lesion uptake of [18F]-CETO in adrenal lesions
研究概览
简要总结
The goal of this clinical trial is to find out whether treatment with baxdrostat changes aldosterone-producing activity in the adrenal glands of people with primary aldosteronism. The study will use specialised imaging to measure changes in the adrenal glands before and after treatment.
Participants will receive baxdrostat for 24 weeks and will be followed for changes in their adrenal imaging, blood pressure and hormone levels. The study will also investigate whether changes caused by treatment continue after baxdrostat is stopped.
This is a single-group study, meaning that all participants receive baxdrostat and there is no placebo or comparison group.
详细描述
Primary aldosteronism (PA) is a common cause of hypertension in which the adrenal glands produce excess aldosterone. In some participants, the source of excess aldosterone can be associated with a small adrenal nodule. Aldosterone synthase, encoded by the CYP11B2 gene, is the enzyme responsible for the final steps of aldosterone production.
Molecular imaging using [18F]-CETO PET-CT can be used to visualise aldosterone-producing tissue in the adrenal glands. This study will investigate whether treatment with the aldosterone synthase inhibitor baxdrostat produces a measurable reduction in aldosterone-producing activity on molecular imaging.
This is an open-label, single-arm experimental medicine study. All participants will receive baxdrostat and there is no placebo or control group. Participants will receive baxdrostat 2 mg once daily for 24 weeks. Molecular imaging will be performed before treatment and following the treatment period, allowing the adrenal imaging signal to be compared within the same participant before and after treatment.
The study is designed to investigate whether pharmacological inhibition of aldosterone synthase is associated with a quantitative reduction in the molecular imaging signal from aldosterone-producing adrenal tissue. It will also investigate whether changes in imaging are associated with changes in biochemical measures of aldosterone production and clinical measures such as blood pressure, and how long suppression of aldosterone production persists after treatment has ended.
[18F]-CETO PET-CT is performed following dexamethasone pretreatment to suppress background uptake and improve visualisation of aldosterone-producing adrenal tissue. The radioligand is administered intravenously and PET imaging is performed together with a low-dose anatomical CT scan. Imaging will be undertaken at St Bartholomew's Hospital or Cambridge University Hospitals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female
- •Age > 18 years at time of signing informed consent.
- •Diagnosed with Primary Aldosteronism (PA) according to Endocrine Society guidelines
- •Presence of one or more adrenal nodules, (diameter 0.5-2.5 cm) on CT, PET-CT, or MRI, with characteristics (e.g. washout) of adenomas
- •Suppressed cortisol after overnight dexamethasone
- •Willing to take baxdrostat for 6 months and attend follow-up visits
- •Willing to undergo PET-CT imaging
- •Estimated glomerular filtration rate ≥ 45 mL/min/1.73m2 at Screening.
- •Serum potassium (K+) level ≥ 3.5 and < 5.0 mmol/L
- •Negative pregnancy test for female participants of childbearing potential
- •Able and willing to provide written consent
排除标准
- •<18 years of age
- •Current or prior treatment (within 1 month before screening) with angiotensin-receptor blockers in combination with ACEIs.
- •Serum sodium level < 135 mmol/L at screening, determined as per central laboratory.
- •The following known secondary causes of hypertension: renal artery stenosis, uncontrolled or untreated hyperthyroidism, uncontrolled or untreated hypothyroidism, pheochromocytoma, Cushing's syndrome, aortic coarctation.
- •New York Heart Association functional Heart Failure class IV at Screening.
- •Known current severe left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy and/or severe aortic valvular disease.
- •Known severe hepatic impairment.
- •Uncontrolled diabetes with HbA1c > 10.0% (86 mmol/mol) at screening.
- •Participants suspected to have severe cardiac hypertrophy.
- •Treatment with any MRAs or potassium-sparing diuretics within 1 month prior to screening.
- •Treatment with potassium binders within 1 month prior to screening.
- •Is expected to receive or is receiving any of the exclusionary drugs such as strong inducers of cytochrome P450 (CYP) 3A, chronic (taken more than 3 times a week for more than 3 months) use of NSAIDs, MRAs or chronic use of systemic steroids.
- •Treatment with K+ supplements is not prohibited but the use should be continuously assessed throughout the trial.
- •Inability or unwillingness to undergo PET-CT imaging
- •Significant comorbidities that would interfere with participation
- •Pregnancy or breastfeeding
- •Unable to give informed consent
研究组 & 干预措施
Baxdrostat
Participants will receive baxdrostat 2 mg once daily for 24 weeks. All participants will receive the same intervention; there is no placebo or control group. Participants will undergo study assessments before, during and after treatment, including molecular imaging and biochemical assessments.
干预措施: baxdrostat (Drug)
结局指标
主要结局
Change in total lesion uptake of [18F]-CETO in adrenal lesions
时间窗: Baseline to approximately 8 months
Change, between pre- and post-baxdrostat PET-CT images, in total \[18F\]-CETO-positive lesion uptake, calculated by multiplying the volume (ml) of each lesion by its mean standardised uptake value (SUVmean) (unitless) and summing these values across all lesions. SUVmean is a dimensionless ratio of measured to injected radioactivity. This calculation generates a single reported value, expressed in SUV·ml, the conventional unit for this measurement. \[Each lesion will be defined according to the 2025 European Association of Nuclear Medicine guideline.\]
次要结局
- Change in SUVmax between pre- and post-baxdrostat PET-CT images(Baseline to approximately 8 months)
- Voxel level change between pre- and post-baxdrostat PET-CT images(Baseline to approximately 8 months)
- Change in the individual components of the primary endpoint: 1. Volume(Baseline to approximately 8 months)
- Change in the individual components of the primary endpoint - 2. mean SUV(Baseline to approximately 8 months)
- Change in whole-adrenal [18F]-CETO uptake(Baseline to approximately 8 months)
- Change in serum aldosterone 12 months after completion of baxdrostat treatment(End of baxdrostat treatment (24 weeks) to 12 months after treatment.)
- Change in plasma renin activity 12 months after completion of baxdrostat treatment(End of baxdrostat treatment (24 weeks) to 12 months after treatment)
- Change in 24-hour urinary tetrahydroaldosterone 12 months after completion of baxdrostat treatment(End of baxdrostat treatment (24 weeks) to 12 months after treatment)
- Change in systolic blood pressure 12 months after completion of baxdrostat treatment(End of baxdrostat treatment (24 weeks) to 12 months after treatment)
- Change in aldosterone-to-renin ratio 12 months after completion of baxdrostat treatment(End of baxdrostat treatment (24 weeks) to 12 months after treatment)
- Change in serum 11-deoxycorticosterone after 12 weeks of baxdrostat treatment(Baseline to 12 weeks)
- Change in serum 11-deoxycorticosterone after 24 weeks of baxdrostat treatment(Baseline to 24 weeks)
- Change in serum 11-deoxycorticosterone 2 months after completion of baxdrostat treatment(Baseline to 2 months after completion of baxdrostat treatment)
- Change in serum 11-deoxycorticosterone 6 months after completion of baxdrostat treatment(Baseline to 6 months after completion of baxdrostat treatment)
- Change in serum 11-deoxycorticosterone 12 months after completion of baxdrostat treatment(Baseline to 12 months after completion of baxdrostat treatment)