Preventing Hypertension and Sympathetic Overactivation by Targeting Phosphate

  • days left to enroll
  • participants needed
  • sponsor
    University of Texas Southwestern Medical Center
Updated on 9 November 2021


An increasing number of studies have indicated that most fast food and common grocery items, contain large amount of inorganic phosphate-based food additives , which are highly absorbable. The long-term cardiovascular consequences of a high phosphate diet are unknown but the existing database implicates phosphate excess as an independent risk factor for cardiovascular events in individuals with and without chronic kidney diseases (CKD). High phosphate consumption clearly induces BP elevation in rats with normal kidneys. However, the mechanisms underlying phosphate-induced hypertension and the relevance of these rodent studies to human hypertension have not been determined. We seek to investigate the role of high phosphate diet in human hypertension and assess the effect of high phosphate diet on muscle sympathetic nerve activity and the exercise pressor reflex.


Animal studies suggest that high phosphate diet raises blood pressure but the mechanism underlying this phenomenon is not known. To study the effect of high phosphorus diet on blood pressure in humans, we will perform randomized crossover studies in stage 1 prehypertensive subjects. To ensure stable Pi intake prior to randomization, Pi consumption will be estimated by food recall during a run-in and washout phase for 2 consecutive days, using the Automated Self-Administered 24-Hour (ASA24) Dietary Assessment Tool ( After the run-in period, all subjects will be maintained on a low Pi diet (700 mg/d) and a low Na diet of approximately 1,930 mg/d throughout the study for 8 weeks. Subjects will also be randomized to receive Sodium Phosphate 2 capsules daily (containing a total of 500 mg of Pi, 372mg of sodium) for 4 weeks during the high Pi phase (total Pi intake 1,200 mg/d) vs 2 capsules of Sodium Chloride (NaCl, containing a total of 372mg of sodium) to match Na content to Sodium Phosphate without extra Pi daily for 4 weeks during the low Pi phase (total Pi intake = 700 mg/d).

The total Na intake during the entire study will be at recommended level of 2,300 mg/d. Investigational drug service at UT Southwestern will dispense Sodium Phosphate vs. NaCl tablets tablets and the study subjects will be blinded to the type of supplement they receive.

During the periods of high and low Pi phases, we will monitor 24-hr UPiV to ensure adherence. Since approximately 70% of ingested Pi is absorbed and excreted in the urine, we expect 24-hr UPiV excretion to be approximately 840 mg during the high Pi phase and 490 mg during the low Pi phase. If 24-hr UPiV is < 800 mg during the high Pi diet or > 500 mg during the low Pi diet, the research dietitian will provide additional counseling to improve adherence to the menu plan. If needed, the research diet will be altered to be more compatible with subject preference. 24-hr UPiV will be reassessed within 1 week in these individuals. If the levels remain below goal, subjects will be excluded from the study.

24-hr urinary Pi, Na, K, Cr, and Ca excretion will be assessed after weeks 2 and 4 of the low and high Pi phases. Serum electrolytes and Pi will be monitored every 2 weeks. Serum FGF23, PTH, and soluble Klotho levels and 24-h ambulatory BP will be obtained after 4 weeks on the study diet. Then, on a separate day, we will assess muscle SNA and BP at rest and during rhythmic handgrip of 30% and 45% each for 3 minutes. Additionally, we will test the role of dietary Pi on the response to isometric exercise by assessing SNA and BP during static handgrip at 30% MVC for 2 minutes followed by post exercise circulatory arrest (PECA). The latter maneuver will maximally activate the metaboreflex. Each exercise intervention will be separated by at least 30 minutes. The order of exercise intervention will be randomized. Subsequently, subjects will stop the first study supplement and undergo washout for 2 weeks. After 2 weeks of washout, they will receive the 2nd study supplement. Measurement of 24-h ambulatory BP, SNA at rest and during handgrip exercise will be repeated in the same fashion.

Condition high blood pressure, High Blood Pressure (Hypertension - Pediatric), Elevated Blood Pressure, Hypertension, arterial hypertension, Vascular Diseases, Diabetes and Hypertension, High Blood Pressure (Hypertension)
Treatment High Phosphate Phase, Low Phosphate Phase
Clinical Study IdentifierNCT03234361
SponsorUniversity of Texas Southwestern Medical Center
Last Modified on9 November 2021


Yes No Not Sure

Inclusion Criteria

(answer must be yes to all to enter trial; check yes or
years of age
Stage 1 Prehypertension (office BP 120-129/80-84 mmHg and normal ABPM <130/80)

Exclusion Criteria

(answer must be no to all to enter trial)
Diabetes mellitus or other systemic disease
Cardiopulmonary disease
Treatment with antihypertensive medications
eGFR< 60 ml/min/1.73m2
Hypersensitivity to nitroprusside or phenylephrine
Psychiatric illness
H/o substance abuse or current smoker
H/o malignancy
Serum Phos <2.4 mg/dL or >4.5 mg/dL
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact



Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note