Racial Differences in the Natriuretic Peptide Response to Glucose Challenge

Healthy Clinical Trial

Official title:

A Study of Racial Differences in Natriuretic Peptides Response to Glucose Challenge

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03072602
• Other study ID #: X16081002
• Status: Completed
• Phase: N/A
• Start date: March 1, 2017
• Est. completion date: October 1, 2018

Study information

• Verified date: June 2023
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to discover any racial dissimilarity in the response of Natriuretic peptide (NP) system to acute metabolic influences such as a high carbohydrate challenge

Description:

Previous studies have shown an association between reduced levels of circulating natriuretic peptides (NPs) and obesity in humans. This association is especially pronounced in those with metabolic syndrome traits and elevated plasma insulin. As previously conducted study has shown that an increase in NPs with weight loss in obese individuals is "primary" and not secondary to alteration in cardiac structure or function.

Previous experimental data suggests that Atrial NP (ANP) has a wide range of favorable metabolic effects including that activation of brown fat and improvement in skeletal muscle oxidative capacity and glucose utilization. New evidence suggests that ANP activation directly modulates insulin sensitivity and energy homeostasis, suggesting that ANP suppression could promote more obesity/insulin resistance. Moreover, ANP exerts potent lipolytic effects in vitro and in vivo. The previous study has shown that a high-carbohydrate challenge in healthy volunteers is associated with a reduction in N-terminal-proANP (NTproANP) but not N-terminal-proB-type NP (NTproBNP) levels. Nonetheless our outcomes were predominantly in Caucasians and warrants replication in other racial groups.

There is no data on the ANP response to high-carbohydrate challenge in African Americans, a racial group with disproportionately greater rates of obesity, insulin resistance, and diabetes as compared to Caucasians. So the investigators have proposed to conduct a pilot study in otherwise healthy, normotensive subjects to examine NP system, especially the effects on MRproANP in response of high-carbohydrate challenge.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: October 1, 2018
• Est. primary completion date: October 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Age 18-40 years

• Blood pressure less than 140/90

• Estimated creatinine clearance >60cc/min

• Willingness to comply with the study diet

Exclusion Criteria:

• History of hypertension

• History of cardiovascular, renal, or liver disease

• Diabetes or use of glucose-lowering medications

• Use of vasoactive or diuretic medications

• Atrial fibrillation

• Anemia (Hematocrit < 41% in men and <35% in women

• Abnormal serum sodium or potassium

• Urine ß-HCG consistent with pregnancy

• Abnormal liver function tests (>3x upper limit of normal)

• Women taking hormonal birth control

• Current smokers

• Regular users of non-steroid anti-inflammatory medications

Related Conditions & MeSH terms

• Healthy
• Metabolic Syndrome
• Natriuretic Peptides

Intervention

Dietary Supplement:
• Study diet
Participants will consume the study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB).

Other:
• Glucose Challenge
Participants will come in fasting state on the main study visit day and will be given 75 gm oral glucose solution to drink, followed by blood collection every hour for next 8 hours.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

References & Publications (4)

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

Patel N, Russell GK, Musunuru K, Gutierrez OM, Halade G, Kain V, Lv W, Prabhu SD, Margulies KB, Cappola TP, Arora G, Wang TJ, Arora P. Race, Natriuretic Peptides, and High-Carbohydrate Challenge: A Clinical Trial. Circ Res. 2019 Nov 8;125(11):957-968. doi — View Citation

Wu C, Arora P, Agha O, Hurst LA, Allen K, Nathan DI, Hu D, Jiramongkolchai P, Smith JG, Melander O, Trenson S, Janssens SP, Domian I, Wang TJ, Bloch KD, Buys ES, Bloch DB, Newton-Cheh C. Novel MicroRNA Regulators of Atrial Natriuretic Peptide Production. Mol Cell Biol. 2016 Jun 29;36(14):1977-87. doi: 10.1128/MCB.01114-15. Print 2016 Jul 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma MRproANP	Change in circulating MRproANP levels in response to glucose challenge in African-Americans (Linear mixed models using MRproANP as the dependent variable and time as the independent variable were used. Values are predicted log MRproANP with 95% CI)	From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days
Secondary	The Difference in Circulating Plasma MRproANP	Change in circulating MRproANP levels in response to glucose challenge between African-Americans and whites (Linear mixed models using MRproANP as the dependent variable and time as the independent variable were used. Values are predicted log MRproANP with 95% CI)	From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days
Secondary	Serum Insulin	The difference in serum insulin levels at 1 hour in response to glucose challenge between African-Americans and whites	At 1 hour after glucose challenge
Secondary	Serum Glucose	The difference in serum glucose levels at 1 hour in response to glucose challenge between African-Americans and whites	At 1 hour after glucose challenge
Secondary	Plasma NTproBNP	Change in circulating NTproBNP levels in response to glucose challenge in African-Americans and Whites (Linear mixed models using MRproANP as the dependent variable and time as the independent variable were used. Values are predicted log NTproBNP with 95% CI)	From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days
Secondary	Change in Neprilysin (Membrane Metalloendopeptidase) mRNA Expression Levels Between African-Americans and Whites	The relative circulating Neprilysin (Membrane Metalloendopeptidase) mRNA quantification (fold change) at baseline between African-Americans and Whites	At baseline