HypertensionPhase 2NCT03234361
Preventing Hypertension and Sympathetic Overactivation by Targeting Phosphate
A Phase 2 study testing High Phosphate Phase and Low Phosphate Phase in people with Hypertension, run by University of Texas Southwestern Medical Center at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypertension
- What is being tested?
- High Phosphate Phase and Low Phosphate Phase
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 94 participants
- Where
- 2 sitesUnited States
- Study dates
- 16 Oct 2017to 30 Sep 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
About this study
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.
Read the detailed description
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.
- Conditions
- Hypertension
- Being tested
- High Phosphate Phase, Low Phosphate Phase
- Keywords
- Hypertension, High phosphorus diet, FGF 23, 24 hour ambulatory blood pressure, Muscle sympathetic nerve
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High Phosphate PhaseDietary supplement
2 capsules of sodium phosphate with 500mg/day of phosphate.
Low Phosphate PhaseDietary supplement
2 capsules of sodium chloride.
| Study group | Role | What they receive |
|---|---|---|
| High Phosphate Phase | Experimental | All subjects will be on a low Pi diet containing 700mg/day of phosphate and 2 capsules of sodium phosphate with 500mg/day of phosphate for 4 weeks. Receives: Dietary Supplement: High Phosphate Phase |
| Low Phosphate Phase | Placebo comparator | All subjects will be on a low Pi diet containing 700mg/day of phosphate and 2 capsules of sodium chloride for 4 weeks. Receives: Dietary Supplement: Low Phosphate Phase |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-hour Blood Pressure measured by Ambulatory Blood Pressure Monitor.
Blood pressure will be measured through an ambulatory blood pressure monitoring device by Space Labs # 90217, worn by each participant after completing each phase, This will suggest if participant's blood pressure increased during high phosphorus phase as compared to low phosphorus phase.
Measured: 4 weeks
Secondary outcomes (1)
Muscle Sympathetic Nerve Activity (MSNA)
MSNA will be measured during both diet phases using microelectrodes inserted in the peroneal nerve. This will assess the impact of phosphate intake on MSNA.
Measured: 4 weeks after high phosphorus and 4 weeks after low phosphorus diet
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2017
- Study start16 Oct 2017
- Primary completion30 Sep 2022
- Study completion30 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wanpen Vongpatanasin, University of Texas Southwestern Medical Center
- Investigators
- Wapen Vongpatanasin, MD, Principal investigator, UT southwestern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03234361
- Sponsor's protocol ID
- STU 012017-052
- Status last verified
- Nov 2022
- First submitted
- 26 Jul 2017
- Last updated
- 4 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Sullivan CM, Leon JB, Sehgal AR. Phosphorus-containing food additives and the accuracy of nutrient databases: implications for renal patients. J Ren Nutr. 2007 Sep;17(5):350-4. doi: 10.1053/j.jrn.2007.05.008.
PubMed 17720105Benini O, D'Alessandro C, Gianfaldoni D, Cupisti A. Extra-phosphate load from food additives in commonly eaten foods: a real and insidious danger for renal patients. J Ren Nutr. 2011 Jul;21(4):303-8. doi: 10.1053/j.jrn.2010.06.021. Epub 2010 Nov 5.
PubMed 21055967Ketteler M, Wolf M, Hahn K, Ritz E. Phosphate: a novel cardiovascular risk factor. Eur Heart J. 2013 Apr;34(15):1099-101. doi: 10.1093/eurheartj/ehs247. Epub 2012 Oct 7. No abstract available.
PubMed 23045267Karp H, Ekholm P, Kemi V, Itkonen S, Hirvonen T, Narkki S, Lamberg-Allardt C. Differences among total and in vitro digestible phosphorus content of plant foods and beverages. J Ren Nutr. 2012 Jul;22(4):416-22. doi: 10.1053/j.jrn.2011.04.004. Epub 2011 Jul 13.
PubMed 21741857Suzuki Y, Mitsushima S, Kato A, Yamaguchi T, Ichihara S. High-phosphorus/zinc-free diet aggravates hypertension and cardiac dysfunction in a rat model of the metabolic syndrome. Cardiovasc Pathol. 2014 Jan-Feb;23(1):43-9. doi: 10.1016/j.carpath.2013.06.004. Epub 2013 Aug 8.
PubMed 23932324Scanni R, vonRotz M, Jehle S, Hulter HN, Krapf R. The human response to acute enteral and parenteral phosphate loads. J Am Soc Nephrol. 2014 Dec;25(12):2730-9. doi: 10.1681/ASN.2013101076. Epub 2014 May 22.
PubMed 24854273Hu MC, Shi M, Cho HJ, Adams-Huet B, Paek J, Hill K, Shelton J, Amaral AP, Faul C, Taniguchi M, Wolf M, Brand M, Takahashi M, Kuro-O M, Hill JA, Moe OW. Klotho and phosphate are modulators of pathologic uremic cardiac remodeling. J Am Soc Nephrol. 2015 Jun;26(6):1290-302. doi: 10.1681/ASN.2014050465. Epub 2014 Oct 17.
PubMed 25326585
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preventing Hypertension and Sympathetic Overactivation by Targeting Phosphate
- ClinicalTrials.gov ID
- NCT03234361
- Acronym / sponsor ID
- STU 012017-052
- Conditions
- Hypertension
- Keywords
- Hypertension, High phosphorus diet, FGF 23, 24 hour ambulatory blood pressure, Muscle sympathetic nerve
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 16 Oct 2017 (actual)
- Primary completion
- 30 Sep 2022 (actual)
- Study completion
- 30 Sep 2022 (actual)
- First posted
- 31 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High Phosphate Phase | Experimental | Dietary Supplement: High Phosphate PhaseAll subjects will be on a low Pi diet containing 700mg/day of phosphate and 2 capsules of sodium phosphate with 500mg/day of phosphate for 4 weeks. |
| Low Phosphate Phase | Placebo comparator | Dietary Supplement: Low Phosphate PhaseAll subjects will be on a low Pi diet containing 700mg/day of phosphate and 2 capsules of sodium chloride for 4 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High Phosphate Phase2 capsules of sodium phosphate with 500mg/day of phosphate. | Dietary supplement | High Phosphate Phase |
| Low Phosphate Phase2 capsules of sodium chloride. | Dietary supplement | Low Phosphate Phase |
Primary outcome
24-hour Blood Pressure measured by Ambulatory Blood Pressure Monitor.
Time frame: 4 weeks
Blood pressure will be measured through an ambulatory blood pressure monitoring device by Space Labs # 90217, worn by each participant after completing each phase, This will suggest if participant's blood pressure increased during high phosphorus phase as compared to low phosphorus phase.
1 secondary outcome
Muscle Sympathetic Nerve Activity (MSNA)
Time frame: 4 weeks after high phosphorus and 4 weeks after low phosphorus diet
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2022.
- Background: PubMed 17720105Sullivan CM, Leon JB, Sehgal AR. Phosphorus-containing food additives and the accuracy of nutrient databases: implications for renal patients. J Ren Nutr. 2007 Sep;17(5):350-4. doi: 10.1053/j.jrn.2007.05.008.
- Background: PubMed 21055967Benini O, D'Alessandro C, Gianfaldoni D, Cupisti A. Extra-phosphate load from food additives in commonly eaten foods: a real and insidious danger for renal patients. J Ren Nutr. 2011 Jul;21(4):303-8. doi: 10.1053/j.jrn.2010.06.021. Epub 2010 Nov 5.
- Background: PubMed 23045267Ketteler M, Wolf M, Hahn K, Ritz E. Phosphate: a novel cardiovascular risk factor. Eur Heart J. 2013 Apr;34(15):1099-101. doi: 10.1093/eurheartj/ehs247. Epub 2012 Oct 7. No abstract available.
- Background: PubMed 21741857Karp H, Ekholm P, Kemi V, Itkonen S, Hirvonen T, Narkki S, Lamberg-Allardt C. Differences among total and in vitro digestible phosphorus content of plant foods and beverages. J Ren Nutr. 2012 Jul;22(4):416-22. doi: 10.1053/j.jrn.2011.04.004. Epub 2011 Jul 13.
- Background: PubMed 23932324Suzuki Y, Mitsushima S, Kato A, Yamaguchi T, Ichihara S. High-phosphorus/zinc-free diet aggravates hypertension and cardiac dysfunction in a rat model of the metabolic syndrome. Cardiovasc Pathol. 2014 Jan-Feb;23(1):43-9. doi: 10.1016/j.carpath.2013.06.004. Epub 2013 Aug 8.
- Background: PubMed 24854273Scanni R, vonRotz M, Jehle S, Hulter HN, Krapf R. The human response to acute enteral and parenteral phosphate loads. J Am Soc Nephrol. 2014 Dec;25(12):2730-9. doi: 10.1681/ASN.2013101076. Epub 2014 May 22.
- Background: PubMed 25326585Hu MC, Shi M, Cho HJ, Adams-Huet B, Paek J, Hill K, Shelton J, Amaral AP, Faul C, Taniguchi M, Wolf M, Brand M, Takahashi M, Kuro-O M, Hill JA, Moe OW. Klotho and phosphate are modulators of pathologic uremic cardiac remodeling. J Am Soc Nephrol. 2015 Jun;26(6):1290-302. doi: 10.1681/ASN.2014050465. Epub 2014 Oct 17.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wapen Vongpatanasin, MD principal investigator
UT southwestern
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing High Phosphate Phase and Low Phosphate Phase in people with Hypertension, run by University of Texas Southwestern Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-hour Blood Pressure measured by Ambulatory Blood Pressure Monitor. (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03234361, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2022.