Preventing Hypertension and Sympathetic Overactivation by Targeting Phosphate
| Status: | Recruiting |
|---|---|
| Conditions: | High Blood Pressure (Hypertension) |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 1/18/2019 |
| Start Date: | October 24, 2017 |
| End Date: | September 30, 2021 |
| Contact: | Debbie Arbique |
| Email: | Debbie.Arbique@UTSouthwestern.edu |
| Phone: | 2146482968 |
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.
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
(https://epi.grants.cancer.gov/asa24/). 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.
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
(https://epi.grants.cancer.gov/asa24/). 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.
Inclusion Criteria: (answer must be yes to all to enter trial; check yes or no)
º ≥ 18 years of age
º 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)
º Diabetes mellitus or other systemic disease
º Cardiopulmonary disease
º Treatment with antihypertensive medications
º eGFR< 60 ml/min/1.73m2
º Pregnancy
º Hypersensitivity to nitroprusside or phenylephrine
º Psychiatric illness
º H/o substance abuse or current smoker
º H/o malignancy
º Serum Phos <2.4 mg/dL or >4.5 mg/dL
We found this trial at
2
sites
5323 Harry Hines Blvd
Dallas, Texas 75235
Dallas, Texas 75235
(214) 648-3111
Principal Investigator: Wanpen Vongpatanasin, MD
Phone: 214-648-3188
Univ of Texas, Southwestern Med Ctr of Dallas The story of UT Southwestern Medical Center...
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1801 Inwood Rd
Dallas, Texas 75390
Dallas, Texas 75390
(214) 645-3300
Principal Investigator: Wanpen Vongpatanasin, MD
Phone: 214-648-2103
University of Texas Southwestern Medical Center UT Southwestern is an academic medical center, world-renowned for...
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