Cardiovascular DiseasesNCT05216042
GENESIS: Genotype Guided - Natriuretic Peptides - Cardiometabolic Health Study
A study testing Study diet, Exercise capacity VO2 max determination and Exercise Challenge in people with Cardiovascular Diseases and Natriuretic Peptides, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Diseases, Natriuretic Peptides, Cardiometabolic Diseases
- What is being tested?
- Study diet, Exercise capacity VO2 max determination and Exercise Challenge
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2022to 30 Apr 2027
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Nehal Vekariya, MS, 205-934-7173, nvekariya@uabmc.edu
Pankaj Arora, MD
About this study
Official title: Atrial Natriuretic Peptide and Regulation of Cardiometabolic Health: A Genotype-Guided Human Physiological Study
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.
Read the detailed description
The heart plays an endocrine role by secreting hormones called Natriuretic Peptides (NPs). NPs directly regulates blood pressure (BP) by causing dilation of blood vessels and removing sodium and water from the body. Apart from blood pressure regulation, previous experimental data suggest that NPs has a wide range of favorable metabolic effects and regulates energy homeostasis, fatty acid oxidation, lipid metabolism, glucose intolerance, insulin sensitivity, and obesity. Investigators have demonstrated that low levels of NPs can increase the risk of developing cardiovascular (CV) events (such as heart failure [HF], stroke, myocardial infarction [MI], or heart attack).
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
- Cardiovascular Diseases, Natriuretic Peptides, Cardiometabolic Diseases, Energy Expenditure, Glucose Metabolism, Exercise
- Being tested
- Study diet, Exercise capacity VO2 max determination, Exercise Challenge, Glucose Challenge
- Keywords
- Natriuretic Peptides, Cardiovascular Diseases, Glucose Metabolism, Energy Expenditure, Exercise, Obesity
- Medical subject headings
- Cardiovascular Diseases, Motor Activity, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Study dietDietary supplement
Participants will consume the study diet for 5 days provided by the clinical research unit's metabolic kitchen (at UAB)
Exercise capacity VO2 max determinationOther
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 ChallengeOther
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 ChallengeOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Dietary Supplement: Study diet; Other: Exercise capacity VO2 max determination; Other: Exercise Challenge; Other: Glucose Challenge |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in MRproANP levels following a standardized oral glucose challenge between the high genotype group and low genotype group.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: About 3 hours on the exercise challenge visit day after consuming study meals for 4 days
Change in the serum glucose levels with standardized exercise protocol between the two genotype groups.
Measured: About 3 hours on the exercise challenge visit day after consuming study meals for 4 days
Change in the serum insulin levels with standardized exercise protocol between the two genotype groups.
Measured: About 3 hours on the exercise challenge visit day after consuming study meals for 4 days
Change in the free fatty acid levels with standardized exercise protocol between the two genotype groups.
Measured: About 3 hours on the exercise challenge visit day after consuming study meals for 4 days
Change in the glycerol levels with standardized exercise protocol between the two genotype groups.
Measured: About 3 hours on the exercise challenge visit day after consuming study meals for 4 days
Change in miR-425 levels with change in NP levels (ANP, MRproANP, BNP, and NTproBNP) following glucose challenge.
Measured: From 1st hour to 8th hour on the main study visit day after consuming study meals for 5 days
Change in miR-425 levels with change in NP levels (ANP, MRproANP, BNP, and NTproBNP) following exercise challenge.
Measured: About 3 hours on the exercise challenge visit day after consuming study meals for 4 days
Change in miR-425 levels with change in serum glucose levels following glucose challenge.
Measured: From 1st hour to 8th hour on the main study visit day after consuming study meals for 5 days
Change in miR-425 levels with change in serum insulin levels following glucose challenge.
Measured: From 1st hour to 8th hour on the main study visit day after consuming study meals for 5 days
Change in miR-425 levels with change in serum glucose levels following exercise challenge.
Measured: About 3 hours on the exercise challenge visit day after consuming study meals for 4 days
Change in miR-425 levels with change in serum insulin levels following exercise challenge.
Measured: About 3 hours on the exercise challenge visit day after consuming study meals for 4 days
Correlation of resting miR-425 levels with REE
Levels of miR-425 measured in 2-ΔΔCT will be assessed and will be related to REE measured in kcal/min
Measured: About 3 hours on the exercise challenge visit day after consuming study meals for 4 days
Change in miR-425 levels with change in NP levels (ANP, MRproANP, BNP, and NTproBNP) following glucose challenge between the two genotype groups.
Measured: From 1st hour to 8th hour on the main study visit day after consuming study meals for 5 days
Change in miR-425 levels with change in NP levels (ANP, MRproANP, BNP, and NTproBNP) following exercise challenge between the two genotype groups.
Measured: About 3 hours on the exercise challenge visit day after consuming study meals for 4 days
Change in miR-425 levels with change in serum glucose levels following glucose challenge between the two genotype groups.
Measured: From 1st hour to 8th hour on the main study visit day after consuming study meals for 5 days
Change in miR-425 levels with change in serum insulin levels following glucose challenge between the two genotype groups.
Measured: From 1st hour to 8th hour on the main study visit day after consuming study meals for 5 days
Change in miR-425 levels with change in serum glucose levels following exercise challenge between the two genotype groups.
Measured: About 3 hours on the exercise challenge visit day after consuming study meals for 4 days
Change in miR-425 levels with change in serum insulin levels following exercise challenge between the two genotype groups.
Measured: About 3 hours on the exercise challenge visit day after consuming study meals for 4 days
Correlation of resting miR-425 levels with REE between the genotype groups.
Levels of miR-425 levels measured in 2-ΔΔCT will be related to the REE measured in kcal/min and will be compared between the genotype groups
Measured: About 3 hours on the exercise challenge visit day after consuming study meals for 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2022
- Study start1 Apr 2022
- Primary completion1 Apr 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Each participant will be enrolled into one of the two groups based on their genotype.
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Pankaj Arora, MD, University of Alabama at Birmingham
- Investigators
- Pankaj Arora, MD, FAHA, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05216042
- Sponsor's protocol ID
- IRB-300008758
- Other IDs
- R01HL163081
- Status last verified
- Oct 2026
- First submitted
- 12 Jan 2022
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 33958126Arora 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.
PubMed 26892417Bajaj 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.
PubMed 29167879Arora 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.
PubMed 25595796Parcha 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.
PubMed 33624057