Trial Title:
Water and Electrolytes Content in HYpertension (WHYSKI) in the SKIn
NCT ID:
NCT06090617
Condition:
Hyperaldosteronism
Hypertension
Aldosterone-producing Adenoma
Aldosteronism
Aldosterone Disorder
Essential Hypertension
Bilateral Adrenal Hyperplasia
Conn Adenoma
Conditions: Official terms:
Adenoma
Adrenocortical Adenoma
Adrenal Hyperplasia, Congenital
Adrenogenital Syndrome
Hypertension
Essential Hypertension
Hyperaldosteronism
Hyperplasia
Conditions: Keywords:
Salt-dependent Hypertension
Primary Aldosteronism
Salt-sensitive
Blood Pressure
TonEBP
Tonicity Enhancing Binding Protein
RAAS
Renin Angiotensin Aldosterone System
BP
GAGs
Glycosaminoglycans
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Procedure
Intervention name:
Skin Biopsy
Description:
Skin biopsies were obtained in all recruited patients.
Arm group label:
Non Hypertensive Control Group
Arm group label:
PA group 1
Arm group label:
PA group 2
Arm group label:
PH Group
Intervention type:
Procedure
Intervention name:
Video-laparoscopic adrenalectomy
Description:
Video-laparoscopic adrenalectomy in those with unilateral PA. (PA group 1)
Arm group label:
PA group 1
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.
Detailed description:
Background. Given the key role of Na+ in the pathophysiology of HT, this study will test
the hypothesis that in PA, which is the paradigm of salt-dependent hypertension, the
skin, Na+, K+ and water content is altered and these alterations are corrected by
surgical cure of PA with video-laparoscopic adrenalectomy. The investigators will use
skin biopsies to directly examine the content of Na+, K+, water, and the
lympho-angiogenetic transcription factor Tonicity Enhancing Binding Protein (TonEBP) mRNA
in the skin, an important reservoir of body Na+, in primary aldosteronism (PA), the
prototype of salt-dependent hypertension.
Methods. The investigators will measure Na+, K+, and water content (by chemical-physical
methods) and TonEBP mRNA copy number (by droplet digital PCR) in skin biopsies from a
sex-mixed cohort of consecutive consenting patients with unilateral PA treated with a
mineralocorticoid receptor antagonist (MRA), before surgery, at doses that correct
hypokalemia and HT in order to refer them for surgery with normokalemia and controlled
high blood pressure, as per protocol at our institution. The participants will be
reassessed in an identical way again after surgical cure.
The investigators expect the dry weight (DW) of the skin specimen obtained at surgery to
be significantly higher than at follow-up and to correlate positively with skin Na+, K+,
and water content. Hence, if these predictions will be verified, the skin cations and
water content will need to be DW-adjusted in order to provide meaningful comparisons
across specimen obtained at different time points. The investigators expect the TonEBP
mRNA copy number to be markedly overexpressed compared to healthy subjects.
The WHYSKI study will provide solid knowledge of the skin Na+, K+ and water content in
patients with arterial salt-dependent hypertension due to PA, PH, and on the effect of
cure of the hyperaldosteronism on these variables. The investigators also expect to
gather novel knowledge on the molecular and cellular mechanisms involved in the
regulation of the content on Na+, K+ and water in a compartment as the skin interstitium
that has been largely neglected thus far.
Criteria for eligibility:
Study pop:
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.
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
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.
- Exclusion of secondary hypertension by hormonal biochemical screening
(aldosterone, renin, ARR<2.06 ng/dL:mIU/L, ACTH, 24h urine cortisol, morning
plasma cortisol level, 24h urine metanephrines and catecholamines).
Control Group
- Age: from 18 to 75 years old
- Signed and dated informed consent form
- Normal arterial blood pressure defined either as:
- None anti-hypertensive drug (s)
- Normal arterial hypertension confirmed by daytime ambulatory blood pressure
monitoring (ABPM), or home blood pressure monitoring, with blood pressure lower
or equal to 135 mmHg for systolic blood pressure and/or lower or equal to 85
mmHg for diastolic blood pressure.
- Exclusion of secondary hypertension by hormonal biochemical screening
(aldosterone, renin, ACTH, 24h urine cortisol, morning plasma cortisol level,
24h urine metanephrines and catecholamines).
Exclusion Criteria:
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.
- Other conditions characterized by possible lymphatic disruption such as lipedema,
cyclic idiopathic edema, lymphedema, and malignancies were also exclusion criteria.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
Azienda Ospedale Università di Padova
Address:
City:
Padova
Zip:
35128
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Gian Paolo Rossi, Prof.
Phone:
0039 0498212279
Email:
segreteria.ipertensioneaopd@aopd.veneto.it
Start date:
January 1, 2021
Completion date:
January 1, 2025
Lead sponsor:
Agency:
University Hospital Padova
Agency class:
Other
Source:
University Hospital Padova
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06090617
