GENESIS: Genotype Guided - Natriuretic Peptides - Cardiometabolic Health Study

NCT05216042 | Recruiting DMC

• 2 other identifiers: IRB-300008758R01HL163081
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Natriuretic Peptides (NP) are hormones produced by the heart, and they have a wide range of favorable metabolic benefits. Lower levels of these hormones are associated with an increased likelihood of the development of diabetes and poor cardiometabolic health. Obese and Black individuals have \~30% lower levels of NP and are at a greater risk of developing cardiovascular (CV) events as compared to lean and White counterparts. Some people have common genetic variations that cause them to have \~20% lower NP levels. Similar to other low NP populations, these individuals with low NP genotype (i.e., carrying a common genetic variation called rs5068) are at a greater risk of developing cardiometabolic diseases. By understanding the NP response following the exercise challenge and the glucose challenge in individuals with genetically lower NP levels will help us understand how to improve cardiometabolic health in them.

Conditions

Cardiometabolic Diseases; Energy Expenditure; Exercise; Obesity; Glucose Metabolism; Cardiovascular Diseases; Natriuretic Peptides

Keywords

Natriuretic Peptides; Cardiovascular Diseases; Glucose Metabolism; Energy Expenditure; Exercise; Obesity

Outcome Measures

Primary Outcomes (4)

• Change in MRproANP levels following a standardized oral glucose challenge between the high genotype group and low genotype group.

  From 1st hour to 8th hour on the main study visit day after consuming study meals for 5 days

• Change in Exercise Energy Expenditure between the high genotype and low genotype group.

  About 3 hours on the exercise challenge visit day after consuming study meals for 4 days

• Change in miR-425 levels following a standardized oral glucose challenge in those with low ANP genotype.

  From 1st hour to 8th hour on the main study visit day after consuming study meals for 5 days

• Change in miR-425 levels following a standardized exercise challenge in those with low ANP genotype.

  About 3 hours on the exercise challenge visit day after consuming study meals for 4 days

Secondary Outcomes (23)

• Change in the NPs (ANP, BNP, NTproBNP) following the glucose challenge between the high genotype group and low genotype group.

  From 1st hour to 8th hour on the main study visit day after consuming study meals for 5 days

• Change in the serum glucose following the glucose challenge between the high genotype group and low genotype group.

  From 1st hour to 8th hour on the main study visit day after consuming study meals for 5 days

• Change in the serum insulin following the glucose challenge between the high genotype group and low genotype group.

  From 1st hour to 8th hour on the main study visit day after consuming study meals for 5 days

• Change in Resting Energy Expenditure (REE) between the two genotype groups.

  About 3 hours on the exercise challenge visit day after consuming study meals for 4 days

• Change in the NPs (ANP, BNP, NTproBNP) with standardized exercise protocol between the two genotype groups.

  About 3 hours on the exercise challenge visit day after consuming study meals for 4 days

Study Arms (2)

Experimental: Low NP Genotype Group

EXPERIMENTAL

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.

Dietary Supplement: Study diet; Other: Exercise capacity VO2 max determination; Other: Exercise Challenge; Other: Glucose Challenge

Active Comparator: High NP Genotype Group

EXPERIMENTAL

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.

Dietary Supplement: Study diet; Other: Exercise capacity VO2 max determination; Other: Exercise Challenge; Other: Glucose Challenge

Interventions

Study diet DIETARY_SUPPLEMENT

Participants will consume the study diet for 5 days provided by the clinical research unit's metabolic kitchen (at UAB)

Active Comparator: High NP Genotype Group; Experimental: Low NP Genotype Group

Exercise capacity VO2 max determination OTHER

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.

Active Comparator: High NP Genotype Group; Experimental: Low NP Genotype Group

Exercise Challenge OTHER

Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill and will also undergo a resting energy expenditure test.

Active Comparator: High NP Genotype Group; Experimental: Low NP Genotype Group

Glucose Challenge OTHER

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; Experimental: Low NP Genotype Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults: Age more than or equal to 18; an equal number of Males and Females
• Consent to the collection of genetic material
• Willing to adhere to the study protocol

You may not qualify if:

• Age \<18, at screening.
• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

Related Publications (5)

• 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.

  PMID: 33958126 BACKGROUND

• 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.

  PMID: 26892417 BACKGROUND

• 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.

  PMID: 29167879 BACKGROUND

• 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.

  PMID: 25595796 BACKGROUND

• 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.

  PMID: 33624057 BACKGROUND

MeSH Terms

Conditions

Cardiovascular Diseases; Motor Activity; Obesity

Condition Hierarchy (Ancestors)

Behavior; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Pankaj Arora, MD, FAHA

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nehal Vekariya, MS

CONTACT

205-934-7173; nvekariya@uabmc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Division of Cardiovascular Disease, Department of Medicine

Model Details: Each participant will be enrolled into one of the two groups based on their genotype.

Study Record Dates

• First Submitted: January 12, 2022
• First Posted: January 31, 2022
• Study Start: April 1, 2022
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

US (1)