Obesity Clinical Trial
— PRECISION-BPOfficial title:
Natriuretic Peptide-Renin-Angiotensin-Aldosterone System Rhythm Axis and Nocturnal Blood Pressure
Obese individuals have a higher prevalence of nocturnal hypertension and non-dipping blood pressure (BP). These conditions are associated with an increased risk of cardiovascular (CV) events and death. 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 this controls the day-night rhythm of BP as well. The NP-BP rhythm relationship is broken down in obese individuals. Obese individuals also have lower circulating NP levels. Lower circulating levels of NPs and elevated renin hormone (a part of the Renin-Angiotensin-Aldosterone System [RAAS]) at nighttime may contribute to the high nocturnal blood pressure in obese individuals which puts 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.
Status | Recruiting |
Enrollment | 160 |
Est. completion date | January 1, 2027 |
Est. primary completion date | January 1, 2027 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 130mmHg and less than or equal to 160mmHg and diastolic blood pressure more than or equal to 80mmHg and less than or equal to 100mmHg. Individuals with hypertension as per the 2017 ACC/AHA Guidelines will be eligible for enrollment Exclusion Criteria: - Age less than 18, at screening. - Systolic BP <130 or >160mmHg at baseline, or diastolic BP <80 or >100 mmHg 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 3 or more classes of hypertension medications on the maximum dose or with resistant hypertension - 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 - Anemia (men, Hct < 38%; women, Hct <36%) - Participants working night shifts or swing shifts - 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) |
Country | Name | City | State |
---|---|---|---|
United States | University of Alabama at Birmingham | Birmingham | Alabama |
Lead Sponsor | Collaborator |
---|---|
University of Alabama at Birmingham | National Heart, Lung, and Blood Institute (NHLBI) |
United States,
Arora P, Reingold J, Baggish A, Guanaga DP, Wu C, Ghorbani A, Song Y, Chen-Tournaux A, Khan AM, Tainsh LT, Buys ES, Williams JS, Heublein DM, Burnett JC, Semigran MJ, Bloch KD, Scherrer-Crosbie M, Newton-Cheh C, Kaplan LM, Wang TJ. Weight loss, saline loading, and the natriuretic peptide system. J Am Heart Assoc. 2015 Jan 16;4(1):e001265. doi: 10.1161/JAHA.114.001265. — View Citation
Arora P, Wu C, Hamid T, Arora G, Agha O, Allen K, Tainsh RET, Hu D, Ryan RA, Domian IJ, Buys ES, Bloch DB, Prabhu SD, Bloch KD, Newton-Cheh C, Wang TJ. Acute Metabolic Influences on the Natriuretic Peptide System in Humans. J Am Coll Cardiol. 2016 Feb 23;67(7):804-812. doi: 10.1016/j.jacc.2015.11.049. — View Citation
Bajaj NS, Gutierrez OM, Arora G, Judd SE, Patel N, Bennett A, Prabhu SD, Howard G, Howard VJ, Cushman M, Arora P. Racial Differences in Plasma Levels of N-Terminal Pro-B-Type Natriuretic Peptide and Outcomes: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. JAMA Cardiol. 2018 Jan 1;3(1):11-17. doi: 10.1001/jamacardio.2017.4207. — View Citation
Parcha V, Kalra R, Li P, Oparil S, Arora G, Arora P. Nocturnal blood pressure dipping in treated hypertensives: insights from the SPRINT trial. Eur J Prev Cardiol. 2022 Feb 19;29(1):e25-e28. doi: 10.1093/eurjpc/zwaa125. No abstract available. — View Citation
Parcha V, Patel N, Gutierrez OM, Li P, Gamble KL, Musunuru K, Margulies KB, Cappola TP, Wang TJ, Arora G, Arora P. Chronobiology of Natriuretic Peptides and Blood Pressure in Lean and Obese Individuals. J Am Coll Cardiol. 2021 May 11;77(18):2291-2303. doi: 10.1016/j.jacc.2021.03.291. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in mean nocturnal systolic blood pressure | Change in mean nocturnal systolic blood pressure will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention. | |
Secondary | Change in percent nocturnal dipping blood pressure | Change in percent nocturnal dipping blood pressure will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention. | |
Secondary | Change in 24-hour mean systolic blood pressure | Change in 24-hour mean systolic blood pressure will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention. | |
Secondary | Change in 24-hour mean diastolic blood pressure | Change in 24-hour mean diastolic blood pressure will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention. | |
Secondary | Change in mean daytime systolic blood pressure | Change in mean daytime systolic blood pressure will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention | |
Secondary | Change in mean daytime diastolic blood pressure | Change in mean daytime diastolic blood pressure will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention | |
Secondary | Change in mean nocturnal diastolic blood pressure | Change in mean nocturnal diastolic blood pressure will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention. | |
Secondary | Change in the daytime, nocturnal, and total urinary excretion parameters (Urine Sodium, Urine Potassium, Urine Creatinine, Urine Albumin). | Change in the daytime, nocturnal, and total urinary excretion parameters (Urine Sodium, Urine Potassium, Urine Creatinine, Urine Albumin) will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention | |
Secondary | Change in 24-hour, daytime, and nocturnal ANP, BNP, NTproBNP, and renin levels | Change in 24-hour, daytime, and nocturnal ANP, BNP, NTproBNP, and renin levels will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention | |
Secondary | Change in 24-hour, daytime, and nocturnal MRproANP levels | Change in 24-hour, daytime, and nocturnal MRproANP levels will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention | |
Secondary | Change in 24-hour, daytime, and nocturnal Aldosterone levels | Change in 24-hour, daytime, and nocturnal Aldosterone levels will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention | |
Secondary | Change in rhythm parameters (mesor, amplitude, and phase) for ANP, BNP, NTproBNP, renin, and melatonin rhythms. | Change in rhythm parameters (mesor, amplitude, and phase) for ANP, BNP, NTproBNP, renin, and melatonin rhythms will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention | |
Secondary | Change in rhythm parameters (mesor, amplitude, and phase) for MRproANP. | Change in rhythm parameters (mesor, amplitude, and phase) for MRproANP will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention | |
Secondary | Change in rhythm parameters (mesor, amplitude, and phase) for aldosterone rhythms. | Change in rhythm parameters (mesor, amplitude, and phase) for aldosterone rhythms will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention | |
Secondary | Change in rhythm parameters (mesor, amplitude, and phase) for cortisol rhythms. | Change in rhythm parameters (mesor, amplitude, and phase) for cortisol rhythms will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention | |
Secondary | Change in rhythm parameters (mesor, amplitude, and phase) for systolic BP, and diastolic BP rhythms. | Change in rhythm parameters (mesor, amplitude, and phase) for systolic BP, and diastolic BP rhythms will be analyzed in the two study arms (morning vs. evening dose of sacubitril/valsartan or valsartan) from baseline and after 28 days of intervention. | At Baseline and after 28 days of intervention |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04243317 -
Feasibility of a Sleep Improvement Intervention for Weight Loss and Its Maintenance in Sleep Impaired Obese Adults
|
N/A | |
Recruiting |
NCT04101669 -
EndoBarrier System Pivotal Trial(Rev E v2)
|
N/A | |
Terminated |
NCT03772886 -
Reducing Cesarean Delivery Rate in Obese Patients Using the Peanut Ball
|
N/A | |
Completed |
NCT03640442 -
Modified Ramped Position for Intubation of Obese Females.
|
N/A | |
Completed |
NCT04506996 -
Monday-Focused Tailored Rapid Interactive Mobile Messaging for Weight Management 2
|
N/A | |
Recruiting |
NCT06019832 -
Analysis of Stem and Non-Stem Tibial Component
|
N/A | |
Active, not recruiting |
NCT05891834 -
Study of INV-202 in Patients With Obesity and Metabolic Syndrome
|
Phase 2 | |
Active, not recruiting |
NCT05275959 -
Beijing (Peking)---Myopia and Obesity Comorbidity Intervention (BMOCI)
|
N/A | |
Recruiting |
NCT04575194 -
Study of the Cardiometabolic Effects of Obesity Pharmacotherapy
|
Phase 4 | |
Completed |
NCT04513769 -
Nutritious Eating With Soul at Rare Variety Cafe
|
N/A | |
Withdrawn |
NCT03042897 -
Exercise and Diet Intervention in Promoting Weight Loss in Obese Patients With Stage I Endometrial Cancer
|
N/A | |
Completed |
NCT03644524 -
Heat Therapy and Cardiometabolic Health in Obese Women
|
N/A | |
Recruiting |
NCT05917873 -
Metabolic Effects of Four-week Lactate-ketone Ester Supplementation
|
N/A | |
Active, not recruiting |
NCT04353258 -
Research Intervention to Support Healthy Eating and Exercise
|
N/A | |
Completed |
NCT04507867 -
Effect of a NSS to Reduce Complications in Patients With Covid-19 and Comorbidities in Stage III
|
N/A | |
Recruiting |
NCT03227575 -
Effects of Brisk Walking and Regular Intensity Exercise Interventions on Glycemic Control
|
N/A | |
Completed |
NCT01870947 -
Assisted Exercise in Obese Endometrial Cancer Patients
|
N/A | |
Recruiting |
NCT06007404 -
Understanding Metabolism and Inflammation Risks for Diabetes in Adolescents
|
||
Recruiting |
NCT05972564 -
The Effect of SGLT2 Inhibition on Adipose Inflammation and Endothelial Function
|
Phase 1/Phase 2 | |
Recruiting |
NCT05371496 -
Cardiac and Metabolic Effects of Semaglutide in Heart Failure With Preserved Ejection Fraction
|
Phase 2 |