Value of Potassium Magnesium Citrate in Preventing and Treating Hypertension in African Americans
Phase: PHASE2
Conditions: Hypertension
Sponsor: University of Texas Southwestern Medical Center

 
 
IND 116,208 Amendment 2, new protocol 
 
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IND 116,208 Amendment 2, new protocol 
September 15, 2021 
Title of Project: Value of Potassium Magnesium Citrate in Preventing and 
Treating Hypertension in African Americans 
 
Investigators  
 
Principal Investigator: Wanpen Vongpatanasin, M.D., Division of 
Cardiology, Department of Medicine, University of Texas Southwestern Medical 
Center 
 
Co-Investigator: Orson W. Moe, M.D., Charles and Jane Pak Center for 
Mineral Metabolism and Clinical Research, University of Texas Southwestern 
Medical Center 
Associate Investigator: Danielle Pittman, R.N., Division of Cardiology, 
University of Texas Southwestern Medical Center 
 
Specific Aims 
   
In the DASH (Dietary Approaches to Stop Hypertension) trials, a diet rich 
in fruits, vegetables, nuts and dairy products, and limited in fat content, was 
shown to be useful in controlling hypertension, particularly in African 
Americans (AA)(Svetkey, 1999). Key components of such a diet are potassium, 
magnesium, and alkali, each of which has been implicated in lowering blood 
pressure. In the original IND 116,208 (STU072012-001), we explored whether 
potassium-magnesium 
citrate 
(KMgCit) 
as 
a 
powder 
pharmaceutical 
formulation (dissolved in water before ingestion) could serve as a surrogate for 
the DASH diet and would lower blood pressure among patients with pre- or 
Stage I hypertension. Unfortunately, the completed study in 30 patients with 
pre- and Stage I hypertension revealed no overall effect of KMgCit on blood 
pressure (Vongpatanasin, 2016). 
    
However, a recent subgroup analysis based on ethnicity of the completed 
study showed that KMgCit significantly reduced 24-h blood pressure compared 
to placebo among African Americans (AA) (n=12), but not in non-AA (n=18). 
Vascular studies in 12 AA revealed that KMgCit produced a marginal reduction 
in central systolic blood pressure. Accordingly, we propose an amendment to 
IND study 116,208 to address the following: 
   
Aim 1. To conduct a double-blinded 2-phase crossover trial, comparing 
the effect on blood pressure of KMgCit vs. Placebo given over 4 weeks each in 
36 new AA patients with pre- or untreated Stage I hypertension. The study will 
seek to confirm the finding of subgroup analysis of an earlier study 
(STU072012-001) in 12 AA patients by showing that KMgCit produces a 
significant reduction in blood pressure in a larger number of AA patients.       

 
 
IND 116,208 Amendment 2, new protocol 
 
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Aim 2. As a secondary goal, to determine the effect of KMgCit on arterial 
stiffness in the same groups of individuals. It is hoped that vascular studies in 
a larger number of AA (n = 36) would reveal a more robust change in central 
systolic blood pressure and indices of arterial stiffness.   
 
Background 
  
DASH Diet  
Hypertension is a major cause of morbidity and mortality. Various drugs 
are available to manage hypertension, such as beta blockers, angiotensin 
converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARB), 
and diuretics. To avoid potential complications of such drugs, lifestyle changes 
– including dietary modifications – have been sought to manage hypertension 
in early stages.  
 
Accordingly, the National Institutes of Health sponsored the DASH trial, 
assessing the value of a diet rich in fruits, vegetables, nuts, and dairy 
products, and limited in fat. At an intermediate sodium intake, this diet 
produced a significant decline in systolic blood pressure of 5 mm and diastolic 
of 2.5 mm (Sacks, 2001).  
The DASH diet is rich in potassium and magnesium. It is also high in 
alkali content since the anions are provided mostly by citrate rather than 
chloride. Considerable data are already available in the literature invoking a 
protective role on hypertension of potassium, magnesium, and alkali 
(extensively reviewed in the original IND 116,208 (STU072012-001)).   
Despite many publications citing efficacy in the control of hypertension, 
the DASH diet never gained wide-spread popularity because of cost and 
demands of long-term dietary adherence. 
  
KMgCit as a Surrogate for the DASH Diet 
Our group has conducted extensive studies with potassium magnesium 
citrate in a tablet form for the prevention of kidney stones (Koenig, 1991, Ruml, 
1999). This preparation was shown to confer equivalent potassium 
bioavailability as potassium chloride, similar magnesium bioavailability as 
magnesium citrate, and slightly greater alkali load than potassium citrate. The 
mineral composition of KMgCit at the recommended daily dose approximated 
the amounts of extra potassium, magnesium and alkali conferred by the DASH 
diet.  
Thus, our original IND 116,208 (STU072012-001) submitted on August 
15, 2012, was designed to explore whether KMgCit might serve as a surrogate 
of the DASH diet and would be useful in the control of hypertension. The tablet 

 
 
IND 116,208 Amendment 2, new protocol 
 
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form previously used in renal stone prevention was impractical due to need for 
daily ingestion of many tablets and difficulty in manufacturing. Accordingly, a 
powder formulation was developed in a sachet form to be dissolved in water 
before ingestion. Designed to be taken twice daily, each sachet contained 20 
meq K, 10 meq Mg and 37 meq citrate.  
In the original IND study, KMgCit was compared with placebo, KCl, and 
KCitrate in 30 patients with pre- or Stage I hypertension treated for 4 weeks 
each in a crossover design (Vongpatanasin, 2016). No significant reduction in 
24-h blood pressure was disclosed between KMgCit and placebo (Fig. 1). 
 
 
Fig. 1. 24-h systolic (top) and diastolic (bottom) blood pressure among 30 patients 
taking placebo, KCl, KCit or KMgCit for 4 weeks each. Bars indicate mean ± SD. The 
potassium preparations delivered 20 meq K bid.  
 
 
  
Subgroup Analysis of Data from the Completed Study  
 
Recently, there has been increased interest regarding the health of 
underserved 
populations, 
including 
AA. 
Hypertension 
and 
related 
cardiovascular-renal complications are more common in African Americans 
than in other ethnicities (Muntner, 2017; Aviv, 2004). In the DASH trial, the 
reduction in blood pressure from the DASH diet was more pronounced among 
AA than in white Americans (Svetkey, 1999). 
Mean Blood Pressure
Placebo
KCl
KCit
KMgCit
mm Hg
50
75
100
125
150

 
 
IND 116,208 Amendment 2, new protocol 
 
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The above circumstance prompted us to conduct a subgroup analysis 
based on ethnicity of blood pressure data from the completed trial 
(Vongpatanasin, 2016) conducted under the original IND 116,208 (STU072012-
001). The subgroup analysis showed that KMgCit induced a significant 
reduction in 24-h systolic blood pressure only in African American subjects. 
Moreover, central systolic blood pressure (SBP) derived from vascular studies 
was reduced marginally by KMgCit in AA but not by other preparations or in 
non-AA.  
     
 
Objective of the Current Proposal 
 
In this IND amendment 2, we wish to confirm the findings from 
retrospective subgroup analysis of the completed study, by enrolling additional 
36 AA untreated patients with pre- or Stage I hypertension to participate in a 
new randomized crossover trial. (This amendment 2, STU2021-0912, differs 
from another amendment to IND to be referred to as amendment 1, 
STU092015-058, that examined the effect of KMgCit in averting complications 
of chlorthalidone therapy in patients with hypertension. This trial is ongoing 
and is expected to be completed by Spring 2022.)  
  
Table 1 compares key features of studies under IND 116,208 
(STU072012-001) – original and the current amendment (STU2021-0912) 2. 
The current amendment proposes to evaluate 36 AA, while the original 
examined 12 AA. Amendment 2 proposes to evaluate only 2 phases (KMgCit vs. 
Placebo) out of 4 from the original. Other features are the same between the 
original and proposed IND.  
 
Table 1. Comparison of Trials under IND 116,208  
 
 
 
 
Original  
 
 
Amendment 2 
Ethnicity  
 
 
AA and non-AA 
 
AA 
No. subjects  
 
AA n=12, 30 total 
 
36 
Phases 
 
 
KMgCit, KCl,  
 
KMgCit, Placebo 
 
 
 
 
KCit, Placebo  
Diagnosis 
 
 
pre- and Stage I 
 
pre- and Stage I 
KMgCit dose, meq/d 
40 K,  20 Mg, 74 citrate 
same 
Placebo 
 
 
microcrystalline cellulose same 
Design 
 
 
crossover 
 
 
crossover 
Treatment duration  
4 weeks 
 
 
4 weeks 
24-h bp monitoring  
yes 
 
 
 
yes 
Vascular studies 
 
yes 
 
 
 
yes 
Other tests  
 
same  
 
 
same  
 
 
 
 
 
  
Significance 

 
 
IND 116,208 Amendment 2, new protocol 
 
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In this protocol (IND 116,208 amendment 2), we want to explore whether 
KMgCit taken during a customary dietary setting, might serve as a “surrogate” 
for the DASH diet to lower blood pressure in African Americans, a group who 
are at increased risk of developing hypertension. Although the original IND 
revealed that KMgCit was ineffective in lowering blood pressure in a combined 
group of hypertensive patients of diverse ethnicities, a retrospective subgroup 
analysis indicated that this drug was effective in AA patients (n=12) though not 
in non-AA (n=18). If KMgCit were to prove effective in a larger number of AA 
patients, it would potentially promise a safe and convenient alternative to the 
DASH diet in population at risk.  
 
Methods of Procedure 
 
Patients to be Studied 
  
Forty-five African American patients with pre- or Stage I hypertension, 
with systolic blood pressure of 120-139 mm or diastolic of < 90 mmHg 
according the 2017 ACC/AHA high BP guideline (Welton, 2018), will be 
recruited into the trial, with the expectation that 36 patients would complete 
both phases of the trial (assuming 20% dropout). They may be AA adult men or 
women (≥ 18 years of age). They may be on ACE inhibitor or ARB, but not on 
spironolactone or diuretic.  
  
Excluded will be patients with  
1. Diabetes mellitus,  
2. Renal impairment (serum creatinine > 1.4 mg/dL), 
3. Any heart diseases such as congestive heart failure or sustained 
arrhythmia, 
4. Chronic NSAID use,  
5. Treatment with diuretics,  
6. Gastroesophageal reflux disease (GERD) requiring treatment with acid 
reducing agent or antacid more than once a week,  
7. Esophageal-gastric ulcer,  
8. Chronic diarrhea, 
9. Hyperkalemia (serum K > 5.0 mmol/L,  
10. Abnormal liver function test (AST or ALT above upper limit of normal 
range),  
11. Subjects who require any potassium supplement on a regular basis for 
any reason, 
12. Pregnancy,  
13. History of major depression, bipolar disorder, or schizophrenia, and  
14. History of substance abuse. 

 
 
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With these exclusions, severe hyperkalemia is unlikely to develop even 
among patients taking ACE inhibitors or ARB. A careful history will be 
taken for symptoms of hyperkalemia at each clinic visit. Patients will be 
asked to contact the principal or associate investigator should they 
experience these symptoms. Serum potassium will be measured at 0, 2 
and 4 weeks of each phase. If serum potassium is > 5.7 meq/L is 
disclosed and found to be clinically relevant by the principal investigator, 
the patient will be withdrawn from the study.  
 
 
Study Design 
 
The patients will participate in a randomized crossover trial comprising 
two phases:   
 
Placebo Phase (microcrystalline cellulose in water)  
 
KMgCit Phase (KMgCit powder in water) 
 
Eligible patients will be block randomized by our research coordinators 
to two equal groups using a computer-generated random number list prior to 
the start of the study. One group will undergo Placebo phase first, followed by 
KMgCit phase. The other group will start with KMgCit phase first followed by 
Placebo.  
 
During each phase, subjects will receive one of the test drugs for 4 
weeks, following by at least 1 week of withdrawal; the other drugs will then be 
given for 4 weeks. Both drugs will be prepared in a similar powder sachet form, 
to make the study double blinded.   
 
 
  
Test Drugs 
  
Placebo will comprise microcrystalline cellulose, equivalent in volume in 
each sachet as other test products (made by Sterling Pharmaceutical Services, 
Dupo, IL, formerly Meta Pharma). During the Placebo Phase, subjects will 
suspend/dissolve the entire content of a sachet in 250 ml water and drink it 
with breakfast and again with dinner.   
  
Potassium 
magnesium 
citrate 
will 
be 
prepared 
by 
Sterling 
Pharmaceutical Services. The content of each sachet will be dissolved in 250 ml 
water and will be drunk with breakfast and again with dinner during the 
KMgCit Phase, to deliver 40 meq K, 20 meq Mg and 74 meq citrate per day.  
 
A taste enhancer will be added to improve tolerance of the test 
medications. Each sachet will be marked by a code, the identity of which will 
be known only to an independent study monitor. Each sachet will be labeled: 
Study drug # --; Diet Study in Hypertension; Investigator: W. Vongpatanasin, 
M.D.  
 

 
 
IND 116,208 Amendment 2, new protocol 
 
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Outline of the Study 
 
During each phase, subjects will take one of the test medications for the 
first four weeks (Table 2). The test drugs will then be stopped for at least 1 
week. Subjects will then take the other test medication for 4 weeks.  
 
Table 2. Study Outline 
 
 
 
 
 
 
 
Week 
0 
 1 
2 
3 
4 
5 
 
Treatment 
         ---------------------------------------------       off 
24-h blood pressure monitoring*  
 
 
 
√ 
Vascular studies 
 
 
 
 
√ 
Urinary chemistry 
 
 
 
 
√ 
Office blood pressure 
√  
  
√ 
 
√ 
Serum electrolytes, chemistry 
√ 
 
√ 
 
√ 
Side effect questionnaire 
√ 
 
√ 
 
√ 
Diet history, body weight  
√ 
 
√ 
 
√ 
“Sachet” count 
 
 
√ 
 
√  
 
*To be also performed at baseline of the first phase, but not in the other phase. 
Subject will pick up 24-hour ambulatory monitor prior to visit 4 visit.  
   
Diet and Other Drugs 
Subjects will be maintained on their customary diet throughout the 
study.  
 
Tests 
24-hour blood pressure monitoring. At baseline of the first phase and on 
week 4 of both phases, 24-hour blood pressures will be recorded in an 
ambulatory setting by using the Spacelab 90217 ambulatory oscillometric 
blood pressure monitor (ABPM) (Spacelabs Medical, Issaquah, WA). Thus, each 
patient will undergo three 24-hour blood pressure monitoring. Recordings will 
be made every 20 minutes during the day and every 30 minutes at night; the 
data during the first hour will be discarded.  
 
 
Noninvasive measurement of central aortic pressure and arterial stiffness 
(vascular studies). During the fourth week of treatment in each phase, arterial 
tonometry and simultaneous ECG will be obtained from the brachial, radial, 
femoral and carotid arteries using a custom pulse transducer device 
manufactured by Cardiovascular Engineering, Inc. The body surface distances 
from the suprasternal notch to the brachial (SSN-B), radial (SSN-R), femoral 
(SSN-F) and carotid (SSN-C) recording sites will be obtained with a tape 

 
 
IND 116,208 Amendment 2, new protocol 
 
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measure. All data will be digitized during the primary acquisition (ECG and 
tonometry pressures at 1000 Hz, audio at 12 kHz) and analyzed in a blinded 
fashion. This technique has been implemented with a high degree of 
reproducibility in several large multicenter clinical trials. The principal 
investigator of this proposal (W. Vongpatanasin) has an extensive experience in 
this procedure (Inrig, 2011).  
 
 
Office blood pressure. During clinic visits at baseline, 2 weeks and 4 
weeks of treatment, the research nurse will obtain blood pressure by using the 
clinic’s oscillometric device (Welch Allyn, Vital Signs, WA). At each visit, three 
blood pressure measurements will be made after subjects sit quietly for at least 
10 minutes. The first reading will be discarded. The 2nd and 3rd measurements 
will be averaged.  
 
 
Urinary chemistry. A 24-hour urine sample will be collected during the 
last week of treatment for “stone risk factors” by the Mineral Metabolism 
Laboratory (Pak, 1985). The tests will include: potassium, ammonium, pH, 
citrate, magnesium, sodium, potassium, calcium, phosphorus, sulfate, 
creatinine, and total volume.  
  
On week 4 of each phase, a fresh spot urine sample will be collected for 
calciprotein particles (CPP, to be measured by A. Pasch) and Klotho 3 (to be 
measured in the laboratory of Moe), and for FGF23 and WNK1 protein and 
mRNA (in Moe’s laboratory) and creatinine. Klotho and FGF23 are emerging as 
major calciophosphoregulatory hormones and are implicated in vascular 
diseases. Urinary CPP might be involved in renal-cardiac injury. Increased 
renal excretion of citrate and magnesium (from potassium magnesium citrate 
treatment) might alter formation of CPP in urine. WNK1 might be a mediator of 
changes in renal (sodium handling) and vascular (resistance) determinants of 
blood pressure that might ensue from potassium and magnesium.  
   
On week 4, a sample from spot urine will be frozen for urinary exosomes 
and aldosterone. Exosomes are shed membranes enclosing cytoplasm from the 
kidney. The measurement will allow us to assess levels of proteins and 
signaling molecules involved in the renal mineral transport. The analysis will 
be performed later in the laboratory of co-investigator (O. Moe), when 
warranted by the results.  
 
 
Serum electrolytes and chemistry. At baseline, 2 weeks and 4 weeks of 
treatment, a venous blood sample will be obtained for electrolytes (potassium, 
sodium, chloride and carbon dioxide), magnesium, creatinine, calcium, 
phosphorus, and albumin. Serum electrolytes will be sent to Quest Diagnostic 

 
 
IND 116,208 Amendment 2, new protocol 
 
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Laboratories for analysis. Serum PTH, 1,25-dihydroxyvitamin D, C-terminal-
telopeptide (CTX) will be measured by the Mineral Metabolism Laboratory. On 
week 4, a sample will be frozen for renin and aldosterone (to be determined 
later when warranted by the results).   
  
On week 4 of each phase, a serum sample will be obtained for Klotho, 
FGF23, and CPP (to be measured by A. Pasch).. Serum CPP might be a marker 
and/or pathogenetic factor for cardiovascular injury. It might also affect 
vascular function.  
 
 
Side effect questionnaire. At baseline, 2 weeks and 4 weeks of treatment, 
the research nurse will complete the side effect questionnaire by interviewing 
the patients (Table 3). This history permits computation of “gastrointestinal 
symptom score”, a quantitative estimate of frequency and severity of 
gastrointestinal side effects (Ruml, 1999). 
 
 
Table 3. Side Effect Assessment 
 
Gastrointestinal Symptoms: 
(Indicate frequencies of none, < 2/wk, 2-7/wk or > 7/wk. 
Indicate severities of none, mild, moderate or severe.) 
 
Frequency 
Severity 
Notes 
 
None 
<2/wk 
2-
7/wk 
>7/wk 
None 
Mild 
Moderate 
Severe 
 
Vomiting 
 
 
 
 
 
 
 
 
 
Nausea 
 
 
 
 
 
 
 
 
 
Belching 
 
 
 
 
 
 
 
 
 
Diarrhea 
 
 
 
 
 
 
 
 
 
Loose BM 
 
 
 
 
 
 
 
 
 
Pain/Cramps 
 
 
 
 
 
 
 
 
 
Melena 
 
 
 
 
 
 
 
 
 
Dyspepsia 
 
 
 
 
 
 
 
 
 
Anorexia 
 
 
 
 
 
 
 
 
 
Dysphagia 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
Other tests. At 2 weeks and 4 weeks of treatment, the research nurse (D. 
Pittman) will collect the test medications and count the number of unused 
packets, to estimate compliance of patients in taking medications. At each visit, 

 
 
IND 116,208 Amendment 2, new protocol 
 
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the research nurse will obtain history of unusual dietary intakes and complete 
side effect questionnaire. Body weight will be measured.  
 
Subject Payment for Participation 
 
At study completion, subject will be paid $500. If subjects stop taking 
part in the study or is withdrawn by the research team, the subject will be paid 
$55 per week of participation. Payment will be issued with UT Southwestern 
Greenphire ClinCard.  
 
Recruitment Methods 
 
Recruitment methods will include database searches (UTSW research 
registry and i2b2), referrals, study flyers, and advertisements in UTSW campus 
newsletter. 
 
Statistical Analysis 
Expectations 
a. 24-hour blood pressure at 4 weeks would reveal a lower BP with 
KMgCit than Placebo. The trend toward a decline would be greater for systolic 
blood pressure than diastolic blood pressure.  
b. Blood pressure at office visits would be lower on KMgCit compared 
with Placebo.  
c. From vascular studies at 4 weeks, carotid to femoral pulse wave 
velocity (PWV) and central aortic blood pressure would be lower on KMgCit 
than on Placebo, while carotid to radial PWV would not be different between 
the phases, indicating specific improvement in aortic elastic function.   
d. On treatment, gastrointestinal symptom score of KMgCit would be 
equivalent to Placebo.  
g. At 4 weeks, 24-hour urinary potassium, pH, citrate and Mg would be 
higher during KMgCit than on Placebo.  
 
 
Subject Safety and Data Monitoring 
Serum potassium will be monitored every 2 weeks during the study. 
Subjects who develop serum K > 5.7 during treatment will have a repeated 
measurement to confirm the value immediately. If repeated potassium level 
remains above 5.7, subject will be excluded from the study. 
  
If serum K is above 6.0 mmol/L, EKG will be obtained immediately and 
the study procedures will be discontinued in these subjects. Subjects will be 
transferred to the emergency department for further evaluation and 
management. Questionnaire will be used to monitor gastrointestinal side 
effects. 
 

 
 
IND 116,208 Amendment 2, new protocol 
 
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If subject is withdrawn early, it may be reasonable to conduct a final 
study visit to complete the study if determined appropriate by the study team. 
This visit will include data points as the 4-week close out visit including 24-hour blood 
pressure monitoring, 24-hour urine collection, fresh urine collection, blood draw, 
vascular studies, symptom questionnaire, and returning study drugs. 
 
 
Conditions under which an Individual Subject will be Withdrawn from the 
Study 
• 
Development of hyperkalemia with serum K > 5.7 during treatment. 
• 
Severe gastrointestinal side effects of more than 2 times per week or 
moderate symptoms of more than 7 times per weeks. 
• 
Withholding of study medication for > 4 weeks for whatever reason. 
• 
Any reason including serious adverse events that results in participant’s 
inability to continue with study protocol and procedures.  
• 
Severe hypertension defined as persistent elevation of systolic BP > 180 
mmHg or diastolic BP > 110 mmHg on 3 consecutive measurements after 
randomization 
• 
Refractory hypotension defined as persistent systolic BP < 90 mmHg   
• 
Pregnancy 
• 
Development of diabetes mellitus or a new medical condition 
necessitating initiation of any diuretics or spironolactone after enrollment in 
the study. 
 
 
Sample Size Calculations 
The sample size was calculated based on the primary outcome of 24h 
SBP. In our previous crossover study, the SD of mean difference in 24h 
SBP within the same patient among our AA group was 7.2. With this SD, the 
sample size of 36 will allow us to detect mean difference in 24h SBP of 
4.9 mmHg between placebo and KMgCit at the a of 0.05 and power of 0.8. 
Assuming a 20% dropout rate, we plan on recruiting 45 patients to enroll 36 
patients completing both phases to drive a robust clinically meaningful finding.   
 
 
Statistical Methods 
 
Descriptive statistics will be used to summarize patient demographic and 
clinical characteristics, as well as the primary and secondary outcomes. All 
analysis will be performed on the principle of intention-to-treat basis, including 
all randomized patients in the allocated sequences for two treatment groups. 
Per protocol analysis will be also conducted on those patients with no major 
protocol deviations. The primary hypothesis of evaluating treatment effect on 
24h BP will be analyzed using a linear mixed-effect model with both fixed and 

 
 
IND 116,208 Amendment 2, new protocol 
 
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random effects. The treatment (KMgCit and Placebo), period and treatment by 
period interaction are included as fixed effects, whereas participant is included 
as a random effect. The sequence effect of the supplement will be tested in this 
model. Similar mixed regression model analysis will be also carried out to 
evaluate secondary outcomes. Data transformation will be made if normality 
assumption is violated. Interim analysis may be performed at 50% completion 
of the trial. All analyses will be performed using R version 4.1.0 (R Foundation 
for Statistical Computing, Vienna, Austria). Two-sided P < 0.05 will be 
considered statistically significant. 
 
References (available in .pdf format upon request)  
 
Aviv A, Hollenberg NK, Weder A. Urinary potassium excretion and sodium 
sensitivity in blacks. Hypert 43: 707-713, 2004. 
  
Hu J, Jiang X, Li N, Yu X, et al. Effects of salt substitute on pulse wave 
analysis among individuals at high cardiovascular risk in rural China: a 
randomized controlled trial. Hypert Res 32: 282-288, 2009. 
Koenig K, Padalino P, Alexandrides G, Pak CYC. Bioavailability of potassium 
and magnesium, and citraturic response from potassium-magnesium citrate. J 
Urol 145: 330-334, 1991. 
 
 
Pak CYC, Skurla C, Harvey JA. Graphic display of urinary risk factors for renal 
stone formation. J Urol 134: 867-870, 1985.   
 
 
Ruml LA, Pak CYC. Effect of potassium magnesium citrate on thiazide-induced 
hypokalemia and magnesium loss. Amer J Kid Dis 34:107-113, 1999. 
 
Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, et al. Effects on blood pressure 
of reduced dietary sodium  and the Dietary Approaches to Stop Hypertension 
(DASH) diet. N Engl J Med 344: 3-10, 2001. 
 
Svetkey LP, Simons-Morton D, Vollmer WM, Appel LJ, Conlin PR, Ryan DH, 
Ard J and Kennedy BM. Effects of dietary patterns on blood pressure: 
subgroup analysis of the Dietary Approaches to Stop Hypertension (DASH) 
randomized clinical trial. Arch Intern Med. 159:285-93, 1999. 
 
Vongpatanasin W, Peri-Okonny P, Velasco A, Arbique D, Wang Z, Ravikumar P, 
Adams-Huet B, Moe OW and Pak CYC. Effects of Potassium Magnesium Citrate 
Supplementation on 24-Hour Ambulatory Blood Pressure and Oxidative Stress 

 
 
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Marker in Prehypertensive and Hypertensive Subjects. Am J Cardiol. 
2016;118:849-853, 2016. 
 
Whelton PK, Carey RM, Aronow WS, Casey DE, Jr., Collins KJ, Dennison 
Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin 
EJ, Muntner P, Ovbiagele B, Smith SC, Jr., Spencer CC, Stafford RS, Taler SJ, 
Thomas RJ, Williams KA, Sr., Williamson JD and Wright JT, Jr. 2017  
 
Investigator Data 
Sponsor: University of Texas Southwestern Medical Center 
 
Principal investigator: Wanpen Vongpatanasin, M.D, 
 
Co-Investigator: Orson Moe, M.D. 
 
Authorized representative of the sponsor: Charles Y.C. Pak, M.D. 
 
Responsible person for trial-related medical decisions: Wanpen Vongpatanasin, 
M.D.  
 
Case report forms and side-effect questionnaire: Danielle Pittman, R.N. 
 
Biostatistician: Yulun Liu 
 
Monitor: Peter Gales 
 
Data manager: Chi Shing Poon