Clinical trial NCT05368090: Endoscopic Ultrasound-guided Radiofrequency Ablation in Primary Aldosteronism
Official title: Endoscopic Ultrasound-guided Radiofrequency Ablation as a Novel Treatment Option Compared With Adrenalectomy in Left-sided Primary Aldosteronism
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Primary Aldosteronism
Aldosterone-Producing Adenoma
Hypercortisolism
Keywords: radio frequency ablation
postoperative hypoaldosteronism
postoperative hypocortisolism
metabolic comorbidity
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
First posted: 2022-05-10
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Four EUS-RFA intervention study groups Group 1: PA with lateralisation to left adrenal and left-sided tumour for EUS-RFA Group 2: PA with suspected left-sided overweight of aldosterone overproduction but not AVS-verified left-sided lateralisation for EUS-RFA as "debulking" procedure Group 3: MACS with unilateral tumour in the left adrenal and unilateral cortisol overproduction verified by AVS, for EUS-RFA Group 4: MACS with bilateral adrenal tumours and AVS-verified bilateral cortisol overproduction for EUS-RFA as "debulking" procedure
Primary purpose: TREATMENT

Brief summary: In this study, the investigators will perform endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) treatment of left-sided adrenal tumours in patients with primary aldosteronism (PA) and in patients with mild autonomous cortisol secretion (MACS). Four different study groups will all receive EUS-RFA of left-sided adrenal tumours. Clinical and biochemical outcome as well as procedural safety will be evaluated. In study patients with verified lateralised aldosterone or cortisol overproduction to the left adrenal, outcome will be compared with control groups performing conventional unilateral adrenalectomy.

Study group 1: PA patients with AVS-verified left sided lateralisation and a EUS-detectable tumour in the left adrenal for EUS-RFA treatment.

Study group 2: PA patient with suspected left-sided overweight of aldosterone production and a EUS-detectable tumour but without strict lateralisation of their aldosterone overproduction, for EUS-RFA treatment as an aldosterone "debulking" procedure.

Study group 3: patients with MACS with AVS-verified lateralisation of cortisol overproduction to the left adrenal and EUS-detectable tumour for EUS-RFA treatment Study group 4: patients with MACS with bilateral adrenal tumours and verified bilateral overproduction of cortisol for EUS-RFA treatment as a cortisol "debulking" procedure.

Detailed description: Primary aldosteronism (PA) is the most common cause of secondary hypertension, and is associated with worse cardiovascular outcome than primary hypertension. Early diagnosis and treatment is paramount to avoid excess morbidity and death. The two main forms of PA are unilateral PA, often caused by an aldosterone-producing adenoma (APA), and bilateral PA. Differentiation between unilateral and bilateral disease determines treatment options. Adrenal vein sampling (AVS) is the recommended procedure to determine PA subtype, unilateral or bilateral. For unilateral PA surgery with unilateral adrenalectomy is recommended treatment. For PA without fulfilling lateralisation criteria, life-long medical treatment is recommended.

Mild autonomous cortisol production (MACS) is present in 20-30% of all adrenal incidentalomas, and is associated with the metabolic syndrome (hypertension, diabetes, obesity and osteoporosis). Therefore these patients carry increased risk of developing cardiovascular disease. Optimal treatment is debated, and based on the degree of MACS, degree of metabolic complications, and the patient's own opinion. Unilateral adrenalectomy is an option if the overproduction is unilateral, but in 15 % of cases, the overproduction is bilateral, and treatment strategy even more troublesome.

The left adrenal is situated in near proximity to the stomach and is easily reached by endoscopic ultrasound (EUS), and may be targeted for RFA, treating an aldosterone- or cortisol-producing tumour only, and spearing the remaining adrenal. In this study we introduce EUS-RFA as a new treatment option in the following patient groups:

Study group 1: PA patients with AVS-verified left sided lateralisation and a EUS-detectable tumour in the left adrenal for EUS-RFA treatment.

Study group 2: PA patient with suspected left-sided overweight of aldosterone production and a EUS-detectable tumour but without strict lateralisation of their aldosterone overproduction, for EUS-RFA treatment as an aldosterone "debulking" procedure.

Study group 3: patients with MACS with AVS-verified lateralisation of cortisol overproduction to the left adrenal and EUS-detectable tumour for EUS-RFA treatment Study group 4: patients with MACS with bilateral adrenal tumours and verified bilateral overproduction of cortisol for EUS-RFA treatment, as a cortisol "debulking" procedure.

For all study groups, if CT scan shows an adrenal nodule to the left adrenal, nodule size must be \< 40 mm and enhancement value must fulfill criteria for a benign adenoma. Patients consenting to the EUS-RFA will have a EUS performed. If EUS of the left adrenal identifies an adrenal nodule, a fine needle tissue sampling will be performed. Thereafter EUS-guided RFA procedure of the tumour will be performed. After RFA treatment, the fine needle tissue sampling will undergo morphological and functional characterisation, including application of specific imaging mass cytometry for detection of aldosterone- or cortisol producing cells.

Clinical and biochemical outcome after EUS-RFA will be evaluated by the international PASO-criteria (PA) or ENSAT/ECE criteria (MACS). In patients with lateralised PA or lateralised MACS, clinical and biochemical outcome and postoperative hypoaldosteronism or hypocortisolism will be compared with conventional unilateral adrenalectomy. Inn all patients, procedural safety will be evaluated.

Eligibility criteria: Inclusion Criteria all groups

* Signed written informed consent
* If CT scan shows an adrenal nodule to the same adrenal as AVS lateralisation result: nodule size \< 4 cm and enhancement criteria for adrenal adenoma (native hounsfield units \< 10 or relative wash-out \> 40% or absolute wash-out \> 60%)

PA unilateral group inclusion criteria:

* Age 18 to 60 years
* PA diagnosis confirmed according to Endocrine Society PA Guideline criteria
* AVS lateralisation to left adrenal (lateralisation index ≥ 4,0)

PA "debulking" group inclusion criteria:

* Age 18 to 70 years
* PA diagnosis confirmed according to Endocrine Society PA Guideline criteria

MACS unilateral and debulking group inclusion criteria:

* Age 18 to 80 years
* MACS diagnosis confirmed according to ENSAT/ECE Guideline criteria
* AVS lateralisation to the left adrenal, and visible left adrenal tumor on CT scan OR bilateral overproduction of cortisol on AVS, and bilateral tumors/hyperplasia on CT scan (debulking)

Exclusion Criteria all groups:

* CT scan suspicion of adrenal malignancy
* Patient refusal to undergo either EUS-RFA or adrenalectomy

Primary outcomes:
measure: Biochemical outcome in PA after EUS-RFA
timeFrame: 1 year
measure: Clinical outcome in PA after EUS-RFA
timeFrame: 1 year
measure: Biochemical outcome in MACS after EUS-RFA
timeFrame: 1 year
measure: Clinical outcome in MACS after EUS-RFA
timeFrame: 1 year
Secondary outcomes:
measure: Number of participants with procedural complications of EUS-RFA compared with unilateral adrenalectomy
timeFrame: 3 months
measure: Length of hospital stay after EUS-RFA compared with after adrenalectomy
timeFrame: 3 months
measure: Number of participants with postoperative hypoaldosteronism
timeFrame: 3 months
measure: Number of participants with postoperative hypocortisolism
timeFrame: 6 weeks
measure: Change from baseline in health-related quality of life at 1 year
timeFrame: 1 year
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland University Hospital
Study officials:
affiliation: Haukeland University Hospital
name: Marianne Grytaas, MD phd
role: PRINCIPAL_INVESTIGATOR
References: