Clinical trial NCT04625569: Genetic of Response to Acute Saline Load Test in Hypertension (Naload)
Official title: Role of Genetic Determinants in the Response to Acute Saline Load Testing in Patients With Essential Hypertension (Naload)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hypertension,Essential
Salt; Excess
Genetic Hypertension
Genetic Predisposition to Disease
Keywords: hypertension
salt sensitivity
genetic
Lead sponsor: Ospedale San Raffaele
Sponsor class: OTHER
First posted: 2020-11-12
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: We enrolled newly discovered, never treated, mild hypertensive male patients in the 'Outpatient Clinic for Hypertension' of San Raffaele Hospital, Milan (Italy)

Brief summary: NHP referred to our outpatient clinic will be enrolled (150 newly recruited) in acute saline test for phenotype characterisation of PNat relationship(7). For each patient we will collect urine and blood samples for standard clinical biochemistry, including electrolytes, creatinine, EO, aldosterone, plasma renin activity, urinary uromodulin (ELISA), urinary and serum uric acid and blood samples for genetic test.

Detailed description: Acute salt load test: after the equilibration period and achievement of a steady state, a constant-rate i.v. infusion of 2 L of 0.9% NaCl was carried out in 2 hours. BP (mean of 3 measurements taken 3 minutes apart) was measured every 30 minutes during the 2 hours of loading and 3 times at 3-min intervals at the end of the infusion. These last 3 BP values were averaged and used in the analysis.

The results of these tests will be added to an already collected database of salt load test collected in the previous studies (already published)

Eligibility criteria: Inclusion Criteria:

* age 18 to 65years;
* body mass index (BMI) \<30 kg/m2;
* Na intake, evaluated as urinary Na excretion of \<300 mEq/24 hours; .office systolic BP (SBP) \>140 mm Hg and diastolic BP (DBP) \>90 mm Hg in 3 consecutive visits to their family doctors.

Exclusion criteria:

* Female patients
* history of myocardial infarction,
* stroke,
* congestive heart failure,
* liver disease, secondary cause of hypertension,
* diabetes,
* severe hypertension (\>160/110 mm Hg),
* abuse of drugs or alcohol, .creatinine clearance \< 80 mL/m.

Secondary forms of hypertension (e.g. primary aldosteronism) were ruled out with specific investigations when deemed appropriate

Primary outcomes:
measure: DMBP120
timeFrame: 120 min
Secondary outcomes:
Other outcomes:
Locations:
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
Study officials:
affiliation: Ospedale San Raffaele
name: Chiara Lanzani, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Trudu M, Janas S, Lanzani C, Debaix H, Schaeffer C, Ikehata M, Citterio L, Demaretz S, Trevisani F, Ristagno G, Glaudemans B, Laghmani K, Dell'Antonio G; SKIPOGH team; Loffing J, Rastaldi MP, Manunta P, Devuyst O, Rampoldi L. Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression. Nat Med. 2013 Dec;19(12):1655-60. doi: 10.1038/nm.3384. Epub 2013 Nov 3.
citation: Citterio L, Delli Carpini S, Lupoli S, Brioni E, Simonini M, Fontana S, Zagato L, Messaggio E, Barlassina C, Cusi D, Manunta P, Lanzani C. Klotho Gene in Human Salt-Sensitive Hypertension. Clin J Am Soc Nephrol. 2020 Mar 6;15(3):375-383. doi: 10.2215/CJN.08620719. Epub 2020 Jan 28.
citation: Lanzani C, Gatti G, Citterio L, Messaggio E, Delli Carpini S, Simonini M, Casamassima N, Zagato L, Brioni E, Hamlyn JM, Manunta P. Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to Low Sodium Intake. Hypertension. 2016 Feb;67(2):342-8. doi: 10.1161/HYPERTENSIONAHA.115.06415. Epub 2015 Dec 14.
citation: Citterio L, Ferrandi M, Delli Carpini S, Simonini M, Kuznetsova T, Molinari I, Dell' Antonio G, Lanzani C, Merlino L, Brioni E, Staessen JA, Bianchi G, Manunta P. cGMP-dependent protein kinase 1 polymorphisms underlie renal sodium handling impairment. Hypertension. 2013 Dec;62(6):1027-33. doi: 10.1161/HYPERTENSIONAHA.113.01628. Epub 2013 Sep 23.