Natriuretic Peptide-Renin-Angiotensin-Aldosterone System Rhythm Axis and Nocturnal Blood Pressure

• Status: Not yet recruiting
• Trial end date: 2027-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Obese individuals have a higher prevalence of nocturnal hypertension and non-dipping blood pressure (BP) and are associated with an increased risk of cardiovascular (CV) events and death as compared with lean individuals. The Natriuretic Peptides (NPs) are hormones produced by the heart which directly regulate BP by causing dilation of blood vessels and by removing sodium and water from the body. NPs have a 24-hour day-night rhythm and controls the day-night rhythm of BP as well. The NP-BP rhythm relationship is broken down in obese individuals. Lower circulating levels of NPs, elevated renin hormone (a part of the Renin-Angiotensin-Aldosterone System [RAAS]) at nighttime may also contribute to the high nocturnal blood pressure in obese individuals and put them at a higher risk of developing CV events. This current study seeks to determine the biological implications of chronopharmacology for synchronizing NP-RAAS-based blood pressure therapy with the physiological diurnal rhythms to restore the normal diurnal rhythm of blood pressure in obese individuals.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Alabama at Birmingham
• Treatments: LCZ 696; Sacubitril and valsartan sodium hydrate drug combination; Valsartan

Criteria

Inclusion Criteria:

• Age more than or equal to 18 years of age

• Body Mass Index between 30 to 45 kg/m^2

• Blood pressure: Systolic BP more than or equal to 140mmHg and less than or equal to 160 mmHg and diastolic blood pressure more than or equal to 80mmHg and less than or equal to 100mmHg.

Exclusion Criteria:

• Age less than 18, at screening.

• Systolic BP <140 or >160 mm Hg at baseline, or diastolic BP <80 or >100 mm Hg at baseline.

• BMI <30 kg/m^2 or >45 kg/m^2;

• History of pulmonary hypertension.

• Have any past or present illness of cardiovascular disease including myocardial infarction, angina, cardiac arrhythmia, diabetes, stroke, TIA, or seizure.

• Participants who are taking more than 2 hypertension medications.

• History of angioedema;

• Estimated glomerular filtration rate (GFR) < 60 ml/min/1.73 m2 (CKD-EPI equation); urine albumin creatinine ratio ≥30 mg/g.

• Hepatic Transaminase (AST and ALT) levels >3x the upper limit of normal;

• Significant psychiatric illness (assessed using validated MINI International Neuropsychiatry Interview questionnaires);

• Anemia (men, Hct < 38%; women, Hct <36%);

• Participants working night shifts or swing shifts.

• Have any past or present illness of sleeping disorders including sleep apnea.

• Women who are pregnant or breastfeeding or who can become pregnant and not practicing an acceptable method of birth control during the study (including abstinence).