Blood Pressure
Conditions
Brief summary
The Potassium Intake-response Trial to Control Hypertension (PITCH) will test the intake-response relationship between potassium supplementation and blood pressure, which may inform clinical guidelines on the optimal level of potassium supplementation for blood pressure lowering among adults with elevated blood pressure or hypertension and dietary guidelines for population intake.
Detailed description
Hypertension is the leading preventable risk factor for cardiovascular disease (CVD) and all-cause mortality, and prevention and treatment of high blood pressure (BP) is crucial for reducing the global burden of CVD. Nonpharmacological interventions, including dietary interventions, are recommended as the primary approach for prevention and treatment of elevated BP and hypertension in US adults. Observational epidemiological studies have reported an inverse association between dietary potassium intake and BP, and clinical trials have documented that potassium supplementation reduces BP. However, previous clinical trials of potassium supplementation and BP have been limited to comparing one single dose of potassium supplementation (mostly 60 mmol/day or 1173 mg/day) to placebo control. Therefore, the optimal level of dietary intake of potassium in the population is currently unknown. In 2019, the National Academies of Science, Engineering, and Medicine updated the Dietary Reference Intake (DRI) recommendations for potassium intake based on the most current evidence associating potassium intake with CVD outcomes, including BP. Limited evidence precluded the DRI Committee from establishing a Chronic Disease Risk Reduction Intake level. The specific goal of the proposed randomized controlled trial is to study the intake-response effect for 4 levels of potassium supplementation on BP among adults with elevated BP or hypertension (defined as average untreated office systolic BP 120-159 mm Hg and diastolic BP \<100 mm Hg). The investigators will test the primary hypothesis that compared with placebo (0 mmol/day potassium supplementation), there is a progressive relationship between increasing doses of oral potassium supplementation (30, 60, and 90 mmol/day or 1173, 2346, 3519 mg/day) and decreasing levels of 24-hour systolic BP from baseline to 12-weeks of follow-up. The investigators will also evaluate effects on daytime (awake) and nighttime (asleep) BP, office systolic and diastolic BP, sodium excretion, and effect mediation and moderation by age, sex, race, central adiposity, baseline urine excretion of sodium and potassium, and change in urine sodium. The results from the proposed trial will fill a critical knowledge gap and may identify the optimal level of potassium supplementation for BP lowering among adults with elevated BP and hypertension. This information can be used to develop dietary guidelines for the prevention and treatment of elevated BP, hypertension, and CVD.
Interventions
DIETARY_SUPPLEMENTPotassium Chloride
Oral administration of potassium chloride tablets
OTHERPlacebo
Oral administration of inert placebo tablets
Sponsors
Tulane University
National Institute of General Medical Sciences (NIGMS)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The proposed trial will employ placebo control and blinding of participants and study staff recording participant information. A Bioinformatics and Biostatistics Core will control the randomization and intervention allocation, preserving the blinding of the investigators and study staff in charge of day-to-day operations. Study participants will receive potassium tablets or placebo and will be unaware of their placebo or dosing assignment.
Intervention model description
Eligible participants will be randomly assigned to placebo or 1 of 3 active intervention groups in a 1:1:1:1 ratio.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women aged \>18 years of any race/ethnicity * Elevated BP or hypertension at screening (untreated office systolic BP 120-159 and diastolic BP \<100 mm Hg) * Willing and able to provide informed consent
Exclusion criteria
* Medical condition in which potassium supplementation is contraindicated: history of heart failure, myocardial infarction, stroke, cardiac arrythmia, chronic kidney disease or estimated glomerular filtration rate \<60 ml/min/1.73 m\^2, diabetes or non-fasting glucose \>200 mg/dL, major depressive disorder (PHQ-9 score ≥15), psychosis, ulcer diseases including esophageal-gastric ulcer, malignancy in the past 5 years, liver disease, organ transplant, Addison's disease (adrenal insufficiency) * Use of medications which may alter serum potassium levels or in which potassium supplementation is contraindicated: antihypertensive agents, antihistamines, antiparkinson agents, antimuscarinic agents, antipsychotics, muscle relaxants, systemic corticosteroids, or chronic use of non-steroidal anti-inflammatory drugs * Serum potassium ≥5.0 mEq/L * Metabolic acidosis * Consumption of \>85th percentile of usual potassium intake among US adults (\>3,750 mg/day) * For women, current pregnancy, breastfeeding, or plans to become pregnant during the study * Consumption of ≥21 alcoholic beverages per week or consumption of ≥6 beverages per occasion * Current or planned residence making it difficult to meet trial requirements or travel to the study site * Current participation in another intervention or pharmaceutical trial * Unable or unwilling to complete 24-hour BP or urinary sample collection * Other concerns regarding ability to meet trial requirements, at the discretion of the investigators or staff
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24-hour Systolic Blood Pressure (BP) From Baseline to 12 Weeks | 12 weeks | Ambulatory blood pressure monitoring will be used to determine 24-hour systolic BP |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24-hour Diastolic Blood Pressure (BP) From Baseline to 12 Weeks | 12 weeks | Ambulatory blood pressure monitoring will be used to determine 24-hour diastolic BP |
| Change in Daytime (Awake) Systolic Blood Pressure (BP) From Baseline to 12 Weeks | 12 weeks | Ambulatory blood pressure monitoring will be used to determine daytime BP |
| Change in Daytime (Awake) Diastolic Blood Pressure (BP) From Baseline to 12 Weeks | 12 weeks | Ambulatory blood pressure monitoring will be used to determine daytime BP |
| Change in Nighttime (Asleep) Systolic Blood Pressure (BP) From Baseline to 12 Weeks | 12 weeks | Ambulatory blood pressure monitoring will be used to determine nighttime BP |
| Change in Nighttime (Asleep) Diastolic Blood Pressure (BP) From Baseline to 12 Weeks | 12 weeks | Ambulatory blood pressure monitoring will be used to determine nighttime BP |
| Change in Office Systolic Blood Pressure (BP) From Baseline to 12 Weeks | 12 weeks | An automated oscillometric device will be used to determine office BP based on the mean of 6 blood pressure values from two 12-week visits minus the mean of 6 values from 2 baseline visits |
| Change in Office Diastolic Blood Pressure (BP) From Baseline to 12 Weeks | 12 weeks | An automated oscillometric device will be used to determine office BP based on the mean of 6 blood pressure values from two 12-week visits minus the mean of 6 values from 2 baseline visits |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJoshua D Bundy, PhD, MPH
Assistant Professor
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 14 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 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 | 0 / 7 | 0 / 6 | 0 / 7 | 0 / 5 |
| other Total, other adverse events | 0 / 7 | 0 / 6 | 0 / 7 | 0 / 5 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 | 0 / 7 | 0 / 5 |
Outcome results
None listed