GENESIS: Genotype Guided - Natriuretic Peptides - Cardiometabolic Health Study
NCT ID: NCT05216042
Last Updated: 2025-07-03
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
NA
200 participants
INTERVENTIONAL
2022-04-01
2027-04-30
Brief Summary
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Detailed Description
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Former studies by the investigators have shown that the NP deficient states such as obese and black individuals contributes to lower energy expenditure, poor metabolic profile and promotes the onset of diabetes. Certain genetic factors contribute to the higher predisposition to cardiometabolic disease in individuals with relative atrial natriuretic peptide (ANP) deficiency. PI and others have identified a common genetic variant, rs5068 is associated with higher plasma ANP levels.
The lack of the rs5068 variant has a comparable effect on ANP levels as seen in obese and black individuals and plays a causal role in cardiometabolic health regulation. The rs5068 variant is only present in 10-12% of the population, thereby leaving nearly 90% of adults vulnerable to the potential adverse cardiometabolic impact of having a relative ANP deficiency. This indicates that a low ANP genotype is associated with a poor metabolic health profile.
Our earlier study, in normotensive healthy young adults, demonstrated that a high glucose meal results in reduce ANP levels by 20-30%, which indicates that ANP is a glucose-responsive hormone. The preliminary data from our ongoing clinical trial has shown increased ANP levels with response to the exercise. The impact of genetically determined low ANP levels on the differences in exercise-induced ANP (beneficial) increase and glucose load-induced suppression of ANP (detrimental) is not known in humans.
Micro-RNA-425 (miR-425) is a negative regulator of ANP and acts in a genotype-specific manner. In our previous study, the investigators have demonstrated that miR-425 levels decreased by 71% following one week on a high-salt diet compared with a low-salt diet in individuals with low ANP genotype, and no change was seen in high ANP genotype individuals. In vitro experiments in animals showed an increase in cardiac miR-425 levels by 22-30%. The negative regulator of ANP also independently negatively regulates the control of energy expenditure. The responsiveness of mir-425 to glucose challenge and exercise challenge (metabolic perturbations) has not been previously evaluated in humans.
Individuals with genetically reduced amounts of ANP will be the focus of our present genotype-guided physiological investigation. Following the glucose and exercise challenges, the investigators will additionally investigate the extent to which miR-425 mediated control of ANP suppression occurs. This study will help in understanding how ANP regulates cardiometabolic health in individuals with genetically lower ANP levels.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
BASIC_SCIENCE
NONE
Study Groups
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Experimental: Low NP Genotype Group
150 healthy adult participants with low NP genotype will be enrolled and each will undergo a physical exam and screening tests to determine participants' eligibility. Participants will consume the study diet for 5 days. On 5th day, the participants will come in for an exercise challenge test. On 6th day, participants will come in a fasting state and drink 75 gm of oral glucose, followed by blood collection every 8 hours.
Study diet
Participants will consume the study diet for 5 days provided by the clinical research unit's metabolic kitchen (at UAB)
Exercise capacity VO2 max determination
Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol and will also undergo a DEXA scan to determine the body mass.
Exercise Challenge
Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill and will also undergo a resting energy expenditure test.
Glucose Challenge
Participants will come in fasting state on day 6th and will be given 75 gm oral glucose solution to drink, followed by blood collection every hour for next 8 hours.
Active Comparator: High NP Genotype Group
50 healthy adult participants with high NP genotype will be enrolled and each will undergo a physical exam and screening tests to determine participants' eligibility. Participants will consume the study diet for 5 days. On 5th day, the participants will come in for an exercise challenge test. On 6th day, participants will come in a fasting state and drink 75 gm of oral glucose, followed by blood collection every 8 hours.
Study diet
Participants will consume the study diet for 5 days provided by the clinical research unit's metabolic kitchen (at UAB)
Exercise capacity VO2 max determination
Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol and will also undergo a DEXA scan to determine the body mass.
Exercise Challenge
Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill and will also undergo a resting energy expenditure test.
Glucose Challenge
Participants will come in fasting state on day 6th and will be given 75 gm oral glucose solution to drink, followed by blood collection every hour for next 8 hours.
Interventions
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Study diet
Participants will consume the study diet for 5 days provided by the clinical research unit's metabolic kitchen (at UAB)
Exercise capacity VO2 max determination
Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol and will also undergo a DEXA scan to determine the body mass.
Exercise Challenge
Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill and will also undergo a resting energy expenditure test.
Glucose Challenge
Participants will come in fasting state on day 6th and will be given 75 gm oral glucose solution to drink, followed by blood collection every hour for next 8 hours.
Eligibility Criteria
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Inclusion Criteria
* Consent to the collection of genetic material
* Willing to adhere to the study protocol
Exclusion Criteria
* BMI \>45 kg/m2.
* Blood pressure more than 140/90 mmHg.
* Participants who are taking more than 2 hypertension medications.
* History of diabetes or fasting plasma glucose \>126 mg/dl or HbA1C\>=6.5% or prior treatment with antidiabetic medication.
* Have any past or present history of cardiovascular diseases (stroke, seizure, myocardial infarction, heart failure, transient ischemic attack, angina, or cardiac arrhythmia)
* 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);
* Estimated GFR \< 60 ml/min/1.73 m2; albumin creatinine ratio ≥30 mg/g
* Hepatic Transaminase (AST and ALT) levels \>3x the upper limit of normal
* Anemia (men, Hct \< 38%; women, Hct \<36%)
* Inability to exercise on a treadmill
18 Years
ALL
Yes
Sponsors
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National Heart, Lung, and Blood Institute (NHLBI)
NIH
University of Alabama at Birmingham
OTHER
Responsible Party
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Pankaj Arora, MD
Assistant Professor, Division of Cardiovascular Disease, Department of Medicine
Principal Investigators
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Pankaj Arora, MD, FAHA
Role: PRINCIPAL_INVESTIGATOR
University of Alabama at Birmingham
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Countries
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Central Contacts
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Facility Contacts
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References
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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.
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.
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.
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.
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.
Other Identifiers
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IRB-300008758
Identifier Type: -
Identifier Source: org_study_id
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