Potassium, Hydration, Cardiovascular, and Kidney Study

Study Overview
=================
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 both water, and to a greater extent, water with a potassium supplement will improve hydration and cardiovascular health in young Black adults (n = 40, 20 females, 20 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 either a) bottled water or b) 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 both water and water along with a potassium supplement (2000mg/day) will improve hydration and cardiovascular health in young Black adults (n = 40, 20 females, 20 males). The investigators will utilize three complementary specific aims to address the investigators' hypotheses: Aim 1: Determine whether water alone, or water with potassium supplementation improve hydration status and reduce circulating copeptin. The investigators hypothesize that two weeks of consuming water, and to a greater extent, 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 and to a greater extent, water and potassium supplementation improve BP and vascular health. The investigators hypothesize that two weeks of consuming water or 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 and/or water with potassium supplementation are efficacious at improving hydration and reducing plasma copeptin in Black adults; 2) the comparative effectiveness of water and potassium supplementation vs. water alone in improving fluid intake and hydration status; 3) whether improving hydration alone or in combination with supplemental potassium improves BP and vascular function in young Black adults; 4) Another area of innovation in the investigators' proposal is determining whether area deprivation index (ADI, i.e., more deprivation) is associated with and 4a) beliefs and practices around hydration and 4a) hydration status.

Official Title
-----------------
The Effects of Water and Potassium Supplementation on Cardiovascular and Kidney Function in Young Black Adults

Conditions
-----------------
Blood Pressure, Hydration

Intervention / Treatment
-----------------
* Dietary Supplement: Water and Potassium supplementation
* Other: Water alone


Participation Criteria
=================
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: After a two-week habitual consumption run-in participants will be randomly assigned to one of two conditions: 1) placebo or 2) potassium supplementation.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Water and Potassium<br>N=20, 10 males, 10 females. Following the two-week habitual run-in period, this group will receive 2000mg potassium supplementation/day for 14 days. This will be achieved by taking capsules filled with potassium citrate powder. | Dietary Supplement: Water and Potassium supplementation<br>* 20 Participants will be given cases of water and instructed to drink at least an extra 1L per day. Additionally, participants will be given 2000 mg of potassium via potassium citrate powder.<br>|
| Active Comparator: Water alone<br>N=20, 10 males, 10 females. Following the two week habitual run-in period, this group will be subject to a placebo supplementation for 14 days. This will be achieved via  6000 mg of dextrose powder in vegan capsules broken out over 6 capsules/day. | Other: Water alone<br>* 20 Participants will be given cases of water and instructed to drink at least an extra 1L per day.<br>|
| No Intervention: Habitual consumption<br>N=40, 20 males, 20 females. All participants will be monitored after two weeks of habitual water and potassium consumption prior to being randomized into two weeks of water alone or water and potassium. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine specific gravity | 24 urine samples will be aliquoted and assessed for urine specific gravity (unitless) | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| Urine osmolality | 24 urine samples will be aliquoted and assessed for urine osmolality in mOsm/kg (AI Osmometer 3D3) | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| Urine flow rate | 24 urine samples will be assessed for urine flow rate based on urine volume and self-reported collection time (ml/min). | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| Plasma copeptin | Plasma copeptin concentration (picomoles per liter) from a resting blood draw | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| 24-hour ambulatory blood pressure | Participants will wear an Oscar2 (with SphygmoCor) ambulatory blood pressure monitor on their upper arm for up to 24-hours preceding their study visit to measure systolic and diastolic blood pressure. The purpose of the ambulatory blood pressure monitoring is to determine blood pressure regulation over an entire day. This blood pressure monitor will be set to automatically take blood pressure every 20 minutes. The monitor records and saves each blood pressure measurement automatically. | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| Pulse wave velocity | The investigators will use the SphygmoCor XCEL system to assess pulse wave velocity (PWV meters per second). A high-fidelity transducer is used to obtain the pressure waveform at the carotid pulse. Distances from the carotid artery sampling site to the femoral artery (upper leg instrumented with a thigh cuff for oscillometric sphygmomanometry), and from the carotid artery to the suprasternal notch will be recorded. PWV will be expressed as cm/s. | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| Pulse wave analysis | The investigators will use the SphygmoCor XCEL system to assess pulse wave analysis (PWA) The sampling site is the brachial artery (upper alarm instrumented with a cuff for oscillometric sphygmomanometer). PWA will be expressed as a percentage (calculated as augmentation pressure divided by the pulse pressure). | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| Brachial blood pressure | Seated rachial blood pressure will be measured triplicate after at least 5 minutes of rest using an oscillometric device (Suntech CT 40) | Change score from habitual consumption to after the hydration interventions (2 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kidney blood velocity | Renal and segmental artery blood velocity will be assessed in the decubitis position using a high-frequency ultrasound probe, typically in the range of 3-5 MHz.Using Spectral Doppler, the peak systolic velocity (PSV) in the renal and segmental arteries will be measured. | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| Plasma Osmolality | Researchers will analyze blood samples for osmolarity (AI Osmometer 3D3) | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| Plasma electrolytes | Researchers will analyze plasma samples for electrolytes (Na, K, Cl) concentration using the SmartLyte Electrolyte Analyzer. The unit of measure for Na, K, and Cl is millimoles per liter (mmol/L). | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| Blood glucose | Researchers will analyze whole blood samples for blood glucose concentration in milligrams per deciliter using Cholestech benchtop analyzer | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| Objective sleep duration | Philips actiwatch spectrum will be used to quantify sleep duration in hours. Participants will wear the watch units for 14 days. The investigators will assess sleep duration and cross-check actigraphy wear times with a sleep diary. | Pre-intervention (14 days) | 
| Objective sleep efficiency | Philips actiwatch spectrum will be used to quantify the percentage of time in bed actually spent sleeping to calculate sleep efficiency. | Pre-intervention (14 days) | 
| Subjective sleep duration | The investigators will use the Pittsburgh Sleep Quality Index (PSQI) to assess sleep duration reflective of the one-month period leading into the study. The global PSQI score can range from 0 to 21 points, however, this outcome specifically refers to self-reported sleep duration in hours. | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| Subjective sleep quality | The investigators will use the Pittsburgh Sleep Quality Index (PSQI) to assess perceived sleep quality reflective of the one-month period leading into the study. The global PSQI score can range from 0 to 21 points. | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| Urine electrolytes | Researchers will analyze 24-hour urine samples for electrolytes (Na, K, Cl) content using the SmartLyte Electrolyte Analyzer. The unit of measure for Na, K, and Cl is milliequivalents (mEq). | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| Inflammatory cytokine responses | Plasma will be used for a multiplex to measure inflammatory cytokines tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein-1, and interleukin-1. These biomarkers will be measured by enzyme-linked immunosorbent assays (ELISAs) from R&D. | Change score from habitual consumption to after the hydration interventions (2 weeks) | 
| Dietary intake | The investigators will instruct participants to complete a diet log for 3 days which will be operationalized with Nutrition Data System for Research (NDSR). | Change score from habitual consumption to after the hydration interventions (2 weeks) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Racial disparities, Hydration, Blood pressure, Vascular function, Potassium