Water and Electrolytes Content in HYpertension (WHYSKI) in the SKIn

NCT06090617 | Recruiting

• 1 other identifier: AOP1615
• Study Type: observational
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

WHYSKI is a prospective within-patient observational clinical study designed to test the hypothesis that alterations of Na+, K+, water, and the lympho-angiogenetic transcription factor Tonicity Enhancing Binding Protein (TonEBP) mRNA take place in the interstitium of the skin compartment of patients with arterial hypertension due to primary aldosteronism in whom hypertension can be surgically cured.

Conditions

Hyperaldosteronism; Hypertension; Aldosterone-producing Adenoma; Aldosteronism; Aldosterone Disorder; Essential Hypertension; Bilateral Adrenal Hyperplasia; Conn Adenoma

Keywords

Salt-dependent Hypertension; Primary Aldosteronism; Salt-sensitive; Blood Pressure; TonEBP; Tonicity Enhancing Binding Protein; RAAS; Renin Angiotensin Aldosterone System; BP; GAGs; Glycosaminoglycans

Outcome Measures

Primary Outcomes (1)

• measure the Na+, K+ and water content in the skin of patients with primary aldosteronism (PA, PA Group), primary (essential) hypertension HT patients (PH Group) and in normotensive patients (Control Group).

  With validated chemical physical methods, we will measure the Na+, K+ and water content in the skin of patients with primary aldosteronism (PA, PA Group), primary (essential) hypertension HT patients (PH Group) and in normotensive patients (Control Group). The skin biopsy will be performed during adrenalectomy in consecutive patients with confirmed unilateral PA (PA Group) and in parallel in the same anatomical region in the PH group and in the Control Group, during surgery for benign diseases. To verify if the cure of PA improves Na+, K+ and water skin clearance in the PA Group the skin biopsy obtained during adrenalectomy will be within-patient compared to that obtained one month after adrenalectomy (PA Group 1). In PA patients found not to have unilateral PA (PA Group 2), the biopsy will be obtained after one month of target medical treatment with canrenone, a mineralocorticoid receptor antagonist.

  Baseline (Surgery), Month 1 after Surgery (for PA Group 1 only)

Secondary Outcomes (1)

• mRNA content of Tonicity-Enhancing Binding Protein TonEBP (also known as NFAT5)

  Baseline (Surgery), Month 1 after Surgery (for PA Group 1 only)

Study Arms (4)

PA group 1

conclusive diagnosis of unilateral PA by the "four corners" criteria: 1. Biochemical evidence of PA 2. Lateralization of aldosterone secretion at adrenal venous sampling. 3. Correction of biochemical values and fall of blood pressure after adrenalectomy. 4. Immunohistochemical demonstration of CYP11B2 positive nodule(s)

Procedure: Skin Biopsy; Procedure: Video-laparoscopic adrenalectomy

PA group 2

Presumed diagnosis of bilateral PA, defined as above but without evidence of lateralized aldosterone excess.

Procedure: Skin Biopsy

PH Group

Primary (essential) Hypertension (PH): conclusively ascertained high blood pressure and exclusion of secondary hypertension

Procedure: Skin Biopsy

Non Hypertensive Control Group

comprising patients submitted to surgery but free of hypertension

Procedure: Skin Biopsy

Interventions

Skin Biopsy PROCEDURE

Skin biopsies were obtained in all recruited patients.

Non Hypertensive Control Group; PA group 1; PA group 2; PH Group

Video-laparoscopic adrenalectomy PROCEDURE

Video-laparoscopic adrenalectomy in those with unilateral PA. (PA group 1)

PA group 1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients referred to either the Endocrine Surgery unit, the Specialized Center for Blood Pressure Disorders of Regione Veneto of the Azienda Ospedale-Università di Padova, or other surgery departments of the same institution were recruited.

You may qualify if:

• PA Group
• Age: 18-75-year-old.
• Signed informed consent form.
• A diagnosis of PA defined as
• o Plasma aldosterone concentration \> 15 ng/dL and aldosterone/renin ratio greater than 20.6 ng/mIU, measured after washout of interfering drugs or after changes of the drug treatment as previously detailed.
• Unilateral or bilateral evidence of PA at adrenal vein sampling
• PH Group
• Age: from 18 to 75 years old
• Signed and dated informed consent form
• Diagnosis of essential hypertension defined either as:
• Use of antihypertensive drug (s)
• Arterial hypertension: in untreated patients this must be confirmed by daytime ambulatory blood pressure monitoring (ABPM), or home blood pressure monitoring, with blood pressure higher or equal to 135 mmHg for systolic blood pressure and/or higher or equal to 85 mmHg for diastolic blood pressure.
• Control Group
• Age: from 18 to 75 years old
• Signed and dated informed consent form

You may not qualify if:

• PA Group
• history of allergy/intolerance to local anesthesia;
• refusal of the patient to undergo skin biopsy;
• refusal of the patient to undergo AVS, and/or contraindications to the general anesthesia that is required for laparoscopic adrenalectomy and/or to undergo adrenalectomy if indicated;
• cortisol-aldosterone co-secreting adenoma or pheochromocytoma. PH Group and Control Group
• Concurrent skin diseases, for example psoriasis, and any pathological conditions that, in the judgement of the investigators, could affect skin electrolyte and water content.
• Subjects with diabetes mellitus type 1 and 2, as drugs affecting the renin-angiotensin-aldosterone system and/or renal Na+ handling as, for example, SGLT-2 inhibitors (gliflozins) 16 were considered to potentially bias results.

Sponsors & Collaborators

• University Hospital Padova: lead

Study Sites (1)

Azienda Ospedale Università di Padova

Padua, 35128, Italy

RECRUITING

Related Publications (6)

• Wiig H, Luft FC, Titze JM. The interstitium conducts extrarenal storage of sodium and represents a third compartment essential for extracellular volume and blood pressure homeostasis. Acta Physiol (Oxf). 2018 Mar;222(3). doi: 10.1111/apha.13006. Epub 2017 Dec 20.

  PMID: 29193764 BACKGROUND

• Rossier BC, Bochud M, Devuyst O. The Hypertension Pandemic: An Evolutionary Perspective. Physiology (Bethesda). 2017 Mar;32(2):112-125. doi: 10.1152/physiol.00026.2016.

  PMID: 28202622 BACKGROUND

• Rossi GP, Bisogni V, Bacca AV, Belfiore A, Cesari M, Concistre A, Del Pinto R, Fabris B, Fallo F, Fava C, Ferri C, Giacchetti G, Grassi G, Letizia C, Maccario M, Mallamaci F, Maiolino G, Manfellotto D, Minuz P, Monticone S, Morganti A, Muiesan ML, Mulatero P, Negro A, Parati G, Pengo MF, Petramala L, Pizzolo F, Rizzoni D, Rossitto G, Veglio F, Seccia TM. The 2020 Italian Society of Arterial Hypertension (SIIA) practical guidelines for the management of primary aldosteronism. Int J Cardiol Hypertens. 2020 Apr 15;5:100029. doi: 10.1016/j.ijchy.2020.100029. eCollection 2020 Jun.

  PMID: 33447758 BACKGROUND

• Elijovich F, Weinberger MH, Anderson CA, Appel LJ, Bursztyn M, Cook NR, Dart RA, Newton-Cheh CH, Sacks FM, Laffer CL; American Heart Association Professional and Public Education Committee of the Council on Hypertension; Council on Functional Genomics and Translational Biology; and Stroke Council. Salt Sensitivity of Blood Pressure: A Scientific Statement From the American Heart Association. Hypertension. 2016 Sep;68(3):e7-e46. doi: 10.1161/HYP.0000000000000047. Epub 2016 Jul 21. No abstract available.

  PMID: 27443572 BACKGROUND

• Torresan F, Rossi FB, Caputo I, Zanin S, Caroccia B, Mattarei A, Paccagnella M, Kohlscheen E, Seccia TM, Iacobone M, Rossi GP. Water and Electrolyte Content in Hypertension in the Skin (WHYSKI) in Primary Aldosteronism. Hypertension. 2024 Dec;81(12):2468-2478. doi: 10.1161/HYPERTENSIONAHA.124.23700. Epub 2024 Oct 2.

  PMID: 39355924 DERIVED

• Torresan F, Rossi FB, Zanin S, Caputo I, Caroccia B, Iacobone M, Rossi GP. Water and Electrolyte Content in Salt-Dependent HYpertension in the SKIn (WHYSKI): Effect of Surgical Cure of Primary Aldosteronism. High Blood Press Cardiovasc Prev. 2024 Jan;31(1):15-21. doi: 10.1007/s40292-023-00614-0. Epub 2023 Dec 21.

  PMID: 38123759 DERIVED

MeSH Terms

Conditions

Hyperaldosteronism; Hypertension; Adrenocortical Adenoma; Essential Hypertension

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Adrenal Cortex Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor of Internal Medicine, MD, FAHA, FACC

Study Record Dates

• First Submitted: October 13, 2023
• First Posted: October 19, 2023
• Study Start: January 1, 2021
• Primary Completion: April 1, 2024
• Study Completion: January 1, 2025
• Last Updated: March 19, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share

Locations

IT (1)