Clinical trial NCT03072602: Racial Differences in the Natriuretic Peptide Response to Glucose Challenge
Official title: A Study of Racial Differences in Natriuretic Peptides Response to Glucose Challenge
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Natriuretic Peptides
Metabolic Syndrome
Keywords: Racial differences
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2017-03-07
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Each participant will be enrolled into one of the two groups by race.
Primary purpose: BASIC_SCIENCE

Brief 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

Detailed 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.

Eligibility criteria: 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 β-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

Primary outcomes:
measure: Plasma MRproANP
timeFrame: From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days
Secondary outcomes:
measure: The Difference in Circulating Plasma MRproANP
timeFrame: From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days
measure: Serum Insulin
timeFrame: At 1 hour after glucose challenge
measure: Serum Glucose
timeFrame: At 1 hour after glucose challenge
measure: Plasma NTproBNP
timeFrame: From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days
measure: Change in Neprilysin (Membrane Metalloendopeptidase) mRNA Expression Levels Between African-Americans and Whites
timeFrame: At baseline
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Pankaj Arora, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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: 10.1161/CIRCRESAHA.119.315026. Epub 2019 Oct 6.