Hypertension
Conditions
Brief summary
Liquid potassium-magnesium citrate (KMgCit) as a pharmaceutical formulation will lower blood pressure among patients with pre- or Stage I hypertension on their customary diet.
Detailed description
In this protocol, the investigators want to explore whether KMgCit taken during a customary dietary setting, might serve as a surrogate for the Dietary Approaches to Stop Hypertension (DASH) diet to lower blood pressure. This study has obvious biomedical importance. Lifestyle modifications are often recommended for pre- or Stage I hypertension. The DASH diet is such a modification that has been shown to be effective. However, this diet is costly and difficult to adhere to long-term. If KMgCit were shown to be effective in lowering blood pressure, it would provide a safe and convenient alternative to the DASH diet.
Interventions
1 sachet mixed with 250 ml water (providing 20 meq K) given at breakfast and again dinner, for a total of 40 meq K/day, for 4 weeks
1 sachet mixed with 250 ml water (providing 20 meq K) given at breakfast and dinner, for a total of 40 meq K/day, for 4 weeks
DRUGPotassium magnesium citrate powder
1 sachet mixed with 250 ml water (providing 20 meq K) given at breakfast and dinner, for a total of 40 meq K/day, for 4 weeks
DRUGPlacebo
1 sachet mixed with 250 ml water given at breakfast and dinner, for a total of 2 sachets/day, for 4 weeks
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women \> 21 years of age * Any Race/Ethnicity * Pre- or Stage I hypertension (BP \>= 120/80 and \<= 159/99)
Exclusion criteria
* Diabetes mellitus * Renal impairment (serum creatinine \> 1.4 mg/dL) * Any heart diseases such as congestive heart failure or sustained arrhythmia * Chronic NSAID use * Treatment with diuretics * Gastroesophageal reflux disease (GERD) requiring treatment with acid reducing agents or antacid more than once a week * Esophageal-gastric ulcer * Chronic diarrhea * Hyperkalemia (serum \> 4.6 meq/L for patients on angiotension-converting-enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), serum K \> 5.0 meq/L for patient not on ACE inhibitors or ARBs) * Abnormal liver function test (aspartate transaminase (AST) or alanine transaminase (ALT) above upper limit of normal range) * Subjects who require any potassium supplement on a regular basis from any reasons * Pregnancy * History of major depression, bipolar disorder, or schizophrenia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour Average Systolic Blood Pressure | 4 weeks | This is the average systolic blood pressure over a 24 hour period. |
| 24-hour Average Diastolic Blood Pressure | 4 weeks | The average diastolic blood pressure over a 24 hour period. |
Secondary
| Measure | Time frame |
|---|---|
| Serum C-terminal Telopeptide (CTX) | 4 weeks |
| 24-hour Urinary Calcium | 4 weeks of treatment |
| Office Systolic Blood Pressure | 4 weeks |
| Central Aortic Systolic Blood Pressure | 4 weeks |
| Central Aortic Diastolic Blood Pressure | 4 weeks |
| Carotid to Femoral Pulse Wave Velocity | 4 weeks |
| Office Diastolic Blood Pressure | 4 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants received the following study drug in random order: Potassium Magnesium Citrate powder, Potassium Citrate powder, Potassium Chloride powder, Placebo. Study medications were taken twice daily after dissolution in 250 ml water. Each phase was followed by at least 1 week of washout. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Baseline | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| 24-hr Daytime Diastolic Blood Pressure | 81 mmHg STANDARD_DEVIATION 11 |
| 24-hr Daytime Heart Rate | 77 beats per minute STANDARD_DEVIATION 11 |
| 24-hr Daytime Systolic Blood Pressure | 129 mmHg STANDARD_DEVIATION 10 |
| 24-hr Diastolic Blood Pressure Average | 79 mmHg STANDARD_DEVIATION 10 |
| 24-hr Heart Rate Average | 76 beats per minute STANDARD_DEVIATION 11 |
| 24-hr Nighttime Diastolic Blood Pressure | 71 mmHg STANDARD_DEVIATION 10 |
| 24-hr Nighttime Heart Rate | 70 beats per minute STANDARD_DEVIATION 11 |
| 24-hr Nighttime Systolic Blood Pressure | 117 mmHg STANDARD_DEVIATION 12 |
| 24-hr Systolic Blood Pressure Average | 126 mmHg STANDARD_DEVIATION 10 |
| Age, Continuous | 54 years STANDARD_DEVIATION 12 |
| BMI | 31 kg/m^2 STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Office Diastolic Blood Pressure | 81 mmHg STANDARD_DEVIATION 8 |
| Office Heart Rate | 72 beats per minute STANDARD_DEVIATION 11 |
| Office Systolic Blood Pressure | 125 mmHg STANDARD_DEVIATION 11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 30 participants |
| Serum 1,25-Dihydroxyvitamin D | 73 pg/ml STANDARD_DEVIATION 34 |
| Serum Albumin | 4.2 g/dl STANDARD_DEVIATION 0.6 |
| Serum Bicarbonate | 23 meq/L STANDARD_DEVIATION 2 |
| Serum Calcium | 9.5 mg/dl STANDARD_DEVIATION 0.5 |
| Serum Chloride (meq/L) | 105 meq/L STANDARD_DEVIATION 2 |
| Serum Creatinine (mg/dl) | 0.9 mg/dl STANDARD_DEVIATION 0.2 |
| Serum Magnesium | 2.2 mg/dl STANDARD_DEVIATION 0.3 |
| Serum Parathyroid Hormone | 59 pg/ml STANDARD_DEVIATION 31 |
| Serum Phosphorus | 3.6 mg/dl STANDARD_DEVIATION 0.1 |
| Serum Potassium | 4.2 meq/L STANDARD_DEVIATION 0.3 |
| Serum Sodium | 139 meq/L STANDARD_DEVIATION 2 |
| Serum Urea Nitrogen | 13.7 mg/dl STANDARD_DEVIATION 3.5 |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 30 | 5 / 30 | 16 / 30 | 4 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 30 | 0 / 30 |
Outcome results
Primary
24-hour Average Diastolic Blood Pressure
The average diastolic blood pressure over a 24 hour period.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Potassium Magnesium Citrate Powder Phase | 24-hour Average Diastolic Blood Pressure | 79 mmHg | Standard Deviation 10 |
| Potassium Citrate Powder Phase | 24-hour Average Diastolic Blood Pressure | 78 mmHg | Standard Deviation 9 |
| Potassium Chloride Powder Phase | 24-hour Average Diastolic Blood Pressure | 78 mmHg | Standard Deviation 9 |
| Placebo Phase | 24-hour Average Diastolic Blood Pressure | 80 mmHg | Standard Deviation 11 |
p-value: 0.2Mixed Models Analysis
Primary
24-hour Average Systolic Blood Pressure
This is the average systolic blood pressure over a 24 hour period.
Time frame: 4 weeks
Population: All participants who completed the study completed all 4 phases.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Potassium Magnesium Citrate Powder Phase | 24-hour Average Systolic Blood Pressure | 127 mmHg | Standard Deviation 11 |
| Potassium Citrate Powder Phase | 24-hour Average Systolic Blood Pressure | 127 mmHg | Standard Deviation 10 |
| Potassium Chloride Powder Phase | 24-hour Average Systolic Blood Pressure | 126 mmHg | Standard Deviation 9 |
| Placebo Phase | 24-hour Average Systolic Blood Pressure | 129 mmHg | Standard Deviation 13 |
p-value: 0.07Mixed Models Analysis
Secondary
24-hour Urinary Calcium
Time frame: 4 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Potassium Magnesium Citrate Powder Phase | 24-hour Urinary Calcium | 158 mg/day | Standard Deviation 94 |
| Potassium Citrate Powder Phase | 24-hour Urinary Calcium | 148 mg/day | Standard Deviation 78 |
| Potassium Chloride Powder Phase | 24-hour Urinary Calcium | 160 mg/day | Standard Deviation 92 |
| Placebo Phase | 24-hour Urinary Calcium | 181 mg/day | Standard Deviation 101 |
p-value: 0.1Mixed Models Analysis
Secondary
Carotid to Femoral Pulse Wave Velocity
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Potassium Magnesium Citrate Powder Phase | Carotid to Femoral Pulse Wave Velocity | 8.7 m/s | Standard Deviation 1.7 |
| Potassium Citrate Powder Phase | Carotid to Femoral Pulse Wave Velocity | 8.8 m/s | Standard Deviation 1.6 |
| Potassium Chloride Powder Phase | Carotid to Femoral Pulse Wave Velocity | 8.7 m/s | Standard Deviation 1.5 |
| Placebo Phase | Carotid to Femoral Pulse Wave Velocity | 8.9 m/s | Standard Deviation 1.8 |
p-value: 0.64Mixed Models Analysis
Secondary
Central Aortic Diastolic Blood Pressure
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Potassium Magnesium Citrate Powder Phase | Central Aortic Diastolic Blood Pressure | 77 mmHg | Standard Deviation 7 |
| Potassium Citrate Powder Phase | Central Aortic Diastolic Blood Pressure | 76 mmHg | Standard Deviation 7 |
| Potassium Chloride Powder Phase | Central Aortic Diastolic Blood Pressure | 77 mmHg | Standard Deviation 9 |
| Placebo Phase | Central Aortic Diastolic Blood Pressure | 79 mmHg | Standard Deviation 8 |
p-value: 0.12Mixed Models Analysis
Secondary
Central Aortic Systolic Blood Pressure
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Potassium Magnesium Citrate Powder Phase | Central Aortic Systolic Blood Pressure | 121 mmHg | Standard Deviation 11 |
| Potassium Citrate Powder Phase | Central Aortic Systolic Blood Pressure | 125 mmHg | Standard Deviation 16 |
| Potassium Chloride Powder Phase | Central Aortic Systolic Blood Pressure | 123 mmHg | Standard Deviation 13 |
| Placebo Phase | Central Aortic Systolic Blood Pressure | 126 mmHg | Standard Deviation 14 |
p-value: 0.18Mixed Models Analysis
Secondary
Office Diastolic Blood Pressure
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Potassium Magnesium Citrate Powder Phase | Office Diastolic Blood Pressure | 81 mmHg | Standard Deviation 9 |
| Potassium Citrate Powder Phase | Office Diastolic Blood Pressure | 81 mmHg | Standard Deviation 8 |
| Potassium Chloride Powder Phase | Office Diastolic Blood Pressure | 80 mmHg | Standard Deviation 9 |
| Placebo Phase | Office Diastolic Blood Pressure | 81 mmHg | Standard Deviation 9 |
p-value: 0.7Mixed Models Analysis
Secondary
Office Systolic Blood Pressure
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Potassium Magnesium Citrate Powder Phase | Office Systolic Blood Pressure | 124 mmHg | Standard Deviation 11 |
| Potassium Citrate Powder Phase | Office Systolic Blood Pressure | 125 mmHg | Standard Deviation 13 |
| Potassium Chloride Powder Phase | Office Systolic Blood Pressure | 127 mmHg | Standard Deviation 11 |
| Placebo Phase | Office Systolic Blood Pressure | 129 mmHg | Standard Deviation 12 |
p-value: 0.16Mixed Models Analysis
Secondary
Serum C-terminal Telopeptide (CTX)
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Potassium Magnesium Citrate Powder Phase | Serum C-terminal Telopeptide (CTX) | 0.46 ng/ml | Standard Deviation 0.28 |
| Potassium Citrate Powder Phase | Serum C-terminal Telopeptide (CTX) | 0.46 ng/ml | Standard Deviation 0.28 |
| Potassium Chloride Powder Phase | Serum C-terminal Telopeptide (CTX) | 0.45 ng/ml | Standard Deviation 0.25 |
| Placebo Phase | Serum C-terminal Telopeptide (CTX) | 0.49 ng/ml | Standard Deviation 0.33 |
p-value: 0.42Mixed Models Analysis