Clinical trial NCT06062017: Potassium, Hydration, Cardiovascular, and Kidney Study (PHACKs)
Official title: The Effects of Water and Potassium Supplementation on Cardiovascular and Kidney Function in Young Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Blood Pressure
Hydration
Vascular Disease Risk
Keywords: Racial disparities
Hydration
Blood pressure
Vascular function
Potassium
Lead sponsor: Auburn University
Sponsor class: OTHER
Collaborators: name: Indiana University
First posted: 2023-10-02
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: After a two-week habitual consumption run-in participants will be assigned to two weeks of water and potassium supplementation.
Primary purpose: PREVENTION

Brief summary: Compared with White Adults, Non-Hispanic Black Adults are at an elevated risk of developing cardiovascular disease (CVD) and end stage chronic-kidney disease (CKD), two of the leading causes of death in the United States. Inadequate hydration status is associated with risk factors for both CVD and CKD. Prior data show that Black individuals are less likely to be adequately hydrated when compared with their White counterparts. Further, socioeconomic factors have been shown to influence hydration practices. Inadequate hydration influences certain hormones that regulate blood volume and impact blood pressure, but increasing potassium intake may provide some positive effects on normalizing these hormones and blood pressure. Black adults, in particular, are more likely to consume less potassium, have inadequate hydration, and tend to have higher blood pressure. As such, there is a critical need for effective strategies to address racial disparities in hydration and resultant health consequences; as well as establish the role of socioeconomic factors contributing to hydration. Therefore, the investigators are seeking to test the investigators' central hypothesis that water with a potassium supplement will improve hydration and cardiovascular health in young White adults (n = 20, 10 females, 10 males), and to a greater extent in young Black Adults (n = 20, 10 females, 10 males. The investigators will assess measures of blood pressure, arterial stiffness, and biomarkers in the urine and blood samples prior to and following a 14-day hydration intervention of 1) bottled water and 2) bottled water with potassium supplementation (2000mg potassium/day).

Detailed description: Compared with White adults, Non-Hispanic Black adults are at an elevated risk of developing cardiovascular disease (CVD) and end-stage chronic kidney disease (CKD) two of the leading causes of mortality in the United States (U.S.). Inadequate hydration status is associated with all-cause mortality and several risk factors for CVD and CKD including obesity, insulin resistance, hypertension, and metabolic syndrome. Prior data demonstrate Black American individuals are more likely to be hypohydrated (i.e., inadequately hydrated) when compared with White individuals. One study in emerging adults (18-25 years old) indicates that Black adults are more likely to be hypohydrated compared with White adults when assessed using gold-standard 24-hour urine collections. Socioeconomic factors influence hydration practices. For example, there are well-justified increased perceptions of unsafe tap water among racial and ethnic minorities. Indeed, the recent Flint, Michigan, and Jackson, Mississippi water crises have raised public awareness over these environmental injustices and ways to increase safe drinking water availability and access. However, there remains a critical need for empirical studies on 1) strategies to address racial disparities in hydration and resultant health consequences; and 2) the role socioeconomic factors in contributing to hydration.

Importantly, hypohydration is associated with increased production of arginine vasopressin (AVP), a peptide hormone produced in the hypothalamus that influences body water balance via anti-diuretic effects. Plasma copeptin is an established surrogate marker of circulating AVP concentration. Plasma copeptin is associated with incident type 2 diabetes, metabolic syndrome, the progression of CKD, and CVD. Some, but not all, studies have demonstrated racial differences in circulating AVP/copeptin. Further, prior studies that aimed at increasing water resulted in reductions in copeptin and improvements in cardiometabolic health. For example, in a cohort with high plasma copeptin, increased water intake also reduced fasting plasma glucose. In a cohort of adults with overweight and obesity, increased water or low-calorie beverage intake reduced fasting plasma glucose and contributed to modest weight loss. Lastly, over 90% of adults do not meet recommendations for potassium intake. Importantly, potassium improves blood pressure (BP), particularly in Black adults, who tend to consume less potassium and have higher BP. Yet, there remains a knowledge gap regarding whether hydration intervention(s) inclusive of water (with or without) potassium could attenuate racial disparities in hydration status and circulating AVP/copeptin. Therefore, the investigators are seeking to test the investigators' central hypothesis that water with a potassium supplement (2000mg/day) will improve hydration and cardiovascular health in White adults (n = 20, 10 females, 10 males), and to a greater extent in young Black Adults (n = 20, 10 females, 10 males). The investigators will utilize three complementary specific aims to address the investigators' hypotheses:

Aim 1: Determine whether water with potassium supplementation improves hydration status and reduces circulating copeptin. The investigators hypothesize that water and potassium supplementation will improve hydration and renal biomarkers, including increased urine volume, and reduced urine specific gravity, urine osmolality, and plasma copeptin.

Aim 2: Determine whether water with potassium supplementation improves BP and vascular health. The investigators hypothesize that water and potassium supplementation will reduce resting laboratory BP and ambulatory BP (awake, asleep, and nocturnal BP dipping), and reduce arterial stiffness assessed via pulse wave velocity.

Aim 3: Determine whether socioeconomic factors are associated with hydration perceptions, knowledge, and practices. The investigators hypothesize that area deprivation index (ADI, i.e., more deprivation) will be associated with hydration perceptions (e.g., greater distrust of tap water) and inadequate hydration assessed by self-reported fluid intake and urine-specific gravity.

In summary, a knowledge gap remains in determining the underlying reasons for the consistently reported racial differences in hydration. To restate, the purpose of this study is to determine 1) whether prescribing water with potassium supplementation is efficacious at improving hydration and reducing plasma copeptin in Black and White adults; 2) whether improving hydration with supplemental potassium improves BP and vascular function in young Black and White adults; 3) Another area of innovation in the investigators' proposal is determining whether area deprivation index (ADI, i.e., more deprivation) is associated with and 3a) beliefs and practices around hydration and 3b) hydration status. 4) We also seek to determine whether the intervention leads to greater improvements in Black adults who are more likely to be underhydrated.

Eligibility criteria: Inclusion Criteria:

* Between the ages of 18-30 years
* Resting blood pressure no higher than 150/90 mmHg
* BMI below 35 kg/m2
* Free of any metabolic disease (e.g., diabetes) kidney disease, pulmonary disorders (e.g., COPD), cardiovascular disease (peripheral vascular, cardiac, or cerebrovascular), no autoimmune diseases, and no history of cancer.

Exclusion Criteria:

* Have any precluding medical conditions (i.e. hemophilia) or medication (Pradaxa, Eliquis, etc.) that prevent participants from giving blood.
* Are currently pregnant or trying to become pregnant.
* take any of the following medications that are contraindicated with potassium supplementation:
* Renin-angiotensin-aldosterone system (RAAS) blockers: Candesartan , Eprosartan, Irbesartan, Losartan, Olmesartan, Telmisartan
* Non -steroidal anti-inflammatory medications: Aspirin, Ibuprofen, Naproxen
* Non-selective beta-blockers: Pindolol, Penbutolol, Oxprenolol, Propranolol, Nadolol, Sotalol, Timolol, Tertatolol
* Calcineurin inhibitors: Cyclosporine
* Heparin (or other blood thinning medications)

Primary outcomes:
measure: Urine specific gravity
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Urine osmolality
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Urine flow rate
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Plasma copeptin
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: 24-hour ambulatory blood pressure
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Pulse wave velocity
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Pulse wave analysis
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Brachial blood pressure
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
Secondary outcomes:
measure: Kidney blood velocity
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Plasma Osmolality
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Plasma electrolytes
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Blood glucose
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Objective sleep duration
timeFrame: Pre-intervention (14 days)
measure: Objective sleep efficiency
timeFrame: Pre-intervention (14 days)
measure: Subjective sleep duration
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Subjective sleep quality
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Urine electrolytes
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Inflammatory cytokine responses
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Dietary intake
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
Other outcomes:
measure: Hemoglobin
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Hematocrit
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
measure: Physical activity
timeFrame: Pre-intervention (intake visit)
measure: Area deprivation index
timeFrame: Pre-intervention (intake visit)
measure: Blood pressure reactivity responses
timeFrame: Change score from habitual consumption to after the hydration interventions (2 weeks)
Locations:
city: Auburn
country: United States
facility: Kinesiology Building
state: Alabama
Study officials:
affiliation: Indiana University
name: Austin T Robinson, Ph.D.
role: STUDY_DIRECTOR
affiliation: Auburn University
name: L. Bruce Gladden, Ph.D.
role: STUDY_DIRECTOR
References:
citation: Robinson AT, Linder BA, Barnett AM, Jeong S, Sanchez SO, Nichols OI, McIntosh MC, Hutchison ZJ, Tharpe MA, Watso JC, Gutierrez OM, Fuller-Rowell TE. Cross-sectional analysis of racial differences in hydration and neighborhood deprivation in young adults. Am J Clin Nutr. 2023 Oct;118(4):822-833. doi: 10.1016/j.ajcnut.2023.08.005. Epub 2023 Aug 22.
citation: Fuller-Rowell TE, Nichols OI, Robinson AT, Boylan JM, Chae DH, El-Sheikh M. Racial disparities in sleep health between Black and White young adults: The role of neighborhood safety in childhood. Sleep Med. 2021 May;81:341-349. doi: 10.1016/j.sleep.2021.03.007. Epub 2021 Mar 12.
citation: Brooks CJ, Gortmaker SL, Long MW, Cradock AL, Kenney EL. Racial/Ethnic and Socioeconomic Disparities in Hydration Status Among US Adults and the Role of Tap Water and Other Beverage Intake. Am J Public Health. 2017 Sep;107(9):1387-1394. doi: 10.2105/AJPH.2017.303923. Epub 2017 Jul 20.
citation: Onufrak SJ, Park S, Sharkey JR, Sherry B. The relationship of perceptions of tap water safety with intake of sugar-sweetened beverages and plain water among US adults. Public Health Nutr. 2014 Jan;17(1):179-85. doi: 10.1017/S1368980012004600. Epub 2012 Oct 26.
citation: Onufrak SJ, Park S, Sharkey JR, Merlo C, Dean WR, Sherry B. Perceptions of tap water and school water fountains and association with intake of plain water and sugar-sweetened beverages. J Sch Health. 2014 Mar;84(3):195-204. doi: 10.1111/josh.12138.
citation: Park S, Onufrak SJ, Cradock AL, Patel A, Hecht C, Blanck HM. Perceptions of Water Safety and Tap Water Taste and Their Associations With Beverage Intake Among U.S. Adults. Am J Health Promot. 2023 Jun;37(5):625-637. doi: 10.1177/08901171221150093. Epub 2023 Jan 6.