Dietary Phosphate Impact on Phosphate Overload

Overseen By John Giacona, PA-C

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Antihypertensives, Vasoactive agents

Disqualifiers: Diabetes, Chronic kidney disease, Cardiopulmonary, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

124 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether consuming phosphate in amounts similar to a typical U.S. diet affects energy levels and muscle function in humans, as previous studies in mice have suggested. Participants will take sodium phosphate (a type of salt) and sodium chloride capsules at different times to compare their effects on the body. The trial seeks healthy individuals without diabetes, kidney disease, or heart issues, and who aren't on medications affecting blood pressure or heart function.

As an unphased trial, this study allows participants to contribute to foundational research that could provide new insights into dietary impacts on health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on antihypertensive medications or any vasoactive agents that affect cardiovascular responses to exercise.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that sodium phosphate often treats low phosphate levels in the blood and is generally safe for this purpose. However, excessive intake can cause serious problems, such as an imbalance in electrolytes, which are minerals that help the body function properly. This imbalance can lead to high phosphate levels in the blood, known as hyperphosphatemia, and other related issues.

The study uses a controlled amount of sodium phosphate, similar to what is safely used in other medical treatments. No evidence links it to cancer, suggesting it does not have long-term harmful effects at the doses used. Participants in clinical trials or treatments with sodium phosphate usually tolerate it well when given in controlled amounts.

While sodium phosphate is generally safe and well-tolerated, adhering to the recommended doses is crucial to avoid serious side effects. Always consult healthcare providers before starting any new treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the trial exploring dietary phosphate's impact on phosphate overload because it aims to understand how manipulating phosphate intake can manage this condition, which is often treated with phosphate binders or dietary restrictions. Unlike current treatments that focus on limiting phosphate absorption, this trial investigates the effects of varying dietary sodium phosphate and sodium chloride intake. By alternating between high and low phosphate phases, researchers hope to uncover new insights into phosphate management, potentially leading to more personalized and effective dietary strategies for those struggling with phosphate overload.

What evidence suggests that this trial's treatments could be effective for phosphate overload?

Research has shown that sodium phosphate can improve aerobic power. One study found that participants who took sodium phosphate experienced a noticeable increase in their VO2max, which measures how well the body uses oxygen during exercise. This suggests that sodium phosphate might enhance the body's oxygen utilization, potentially boosting exercise performance. The study also reported improvements in other exercise-related areas, indicating benefits for those seeking to enhance physical performance. However, while these findings are encouraging, they have not been confirmed for the specific issue of phosphate overload in humans. Participants in this trial will receive sodium phosphate in one phase and sodium chloride in another to assess the impact on phosphate overload. ^{4 6 7 8 9}

Who Is on the Research Team?

Wanpen Vongpatanasin, MD

Principal Investigator

[e-mail]

Are You a Good Fit for This Trial?

This trial is for healthy adults without diabetes, chronic kidney disease, heart disease, or those on blood pressure medications. Participants should not be pregnant, have normal phosphate levels in their blood, and no history of psychiatric illness, active cancer or substance abuse including smoking.

Inclusion Criteria

I am healthy without diabetes, kidney disease, heart disease, or taking heart-related meds.

Exclusion Criteria

Any history of substance abuse or current cigarette use

I have a history of cancer.

Serum phosphorus < 2.4 or > 4.5 mg/dL.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in and Washout

Participants undergo a run-in and washout phase to stabilize dietary phosphate intake, estimated by food recall for 2 consecutive days

2 days

Low Phosphate Phase

Participants receive a low phosphate diet (700 mg/d) and Sodium Chloride capsules for 4 weeks

4 weeks

Bi-weekly visits for serum electrolytes and Pi monitoring

High Phosphate Phase

Participants receive a high phosphate diet (1,200 mg/d) and Sodium Phosphate capsules for 4 weeks

4 weeks

Bi-weekly visits for serum electrolytes and Pi monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sodium Chloride
• Sodium Phosphate

Trial Overview

The study tests the effects of dietary phosphate (found in many foods) on exercise ability and belly fat. It compares taking sodium phosphate to sodium chloride (table salt), looking at how these supplements might affect physical activity and metabolism.

How Is the Trial Designed?

Group I: Sodium Phosphate (NaPO4) then sodium chloride (NaCl) Experimental Treatment 2 Interventions

Participants will be asked to take 2 capsules daily of Sodium Phosphate (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). Then, participants will be asked to take 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).

Group II: NaCl then NaPO4 Experimental Treatment 2 Interventions

Participants will be asked to take 2 capsules daily of Sodium Chloride (NaCl, containing a total of 372mg of sodium) for 4 weeks during the low Pi phase (total Pi intake = 700 mg/d). Then, participants will be asked to take 2 capsules of Sodium Phosphate daily for 4 weeks Sodium Phosphate (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).

Sodium Phosphate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Sodium Phosphate for:

• Electrolyte imbalance
• Acidosis
• Urinary acidification

Approved in European Union as Sodium Phosphate for:

• Electrolyte disturbances
• Metabolic acidosis

Approved in Canada as Sodium Phosphate for:

• Electrolyte imbalance
• Acidosis

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

Smaller individuals (weighing <55 kg) experience significantly higher serum phosphate levels after consuming sodium phosphate preparations compared to larger individuals (weighing >100 kg), indicating a potential risk for complications.

The study suggests that lower body weight may increase the risk of calcium-phosphate nephropathy due to elevated phosphate levels, even when hydration is carefully monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased serum phosphate levels and calcium fluxes are seen in smaller individuals after a single dose of sodium phosphate colon cleansing solution: a pharmacokinetic analysis. Ehrenpreis, ED.[2013]

Oral sodium phosphate is an effective and well-tolerated agent for colonic cleansing, as shown in multiple clinical trials, but it can cause shifts in intravascular volume and lead to hyperphosphatemia, which may result in hypocalcemia.

A review of cases at the authors' institution found four patients with adverse events related to oral sodium phosphate, primarily in those with pre-existing health conditions or who received higher doses than recommended, highlighting the need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recognizing the clinical contraindications to the use of oral sodium phosphate for colon cleansing: a case study. Hookey, LC., Vanner, S.[2019]

In a study of 311 patients undergoing colonoscopy, oral sodium phosphate solution (OSPS) caused a slight increase in serum creatinine levels, indicating a minor impact on renal function, but this change was not clinically significant.

The proportion of patients experiencing a significant increase (50% or more) in serum creatinine was similar between those using OSPS and those using polyethylene glycol (PEG), suggesting that OSPS has minimal renal toxicity in patients with baseline creatinine levels below 1.5 mg/dL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The renal safety of bowel preparations for colonoscopy: a comparative study of oral sodium phosphate solution and polyethylene glycol. Singal, AK., Rosman, AS., Post, JB., et al.[2018]

Dietary phosphate influences food intake and appetite, as changes in phosphate load corresponded with variations in digestive system distention, indicating a direct effect on appetite.

Rats receiving phosphate showed specific growth effects in the liver and fat tissue, and their serum contained a factor that inhibits sodium-dependent phosphate transport in kidney cells, suggesting a complex interaction between dietary phosphate and renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distinctive features of dietary phosphate supply. Landsman, A., Lichtstein, D., Ilani, A.[2013]

A survey of 190 medical and nursing students revealed that only 6.9% were aware of phosphate in soda drinks and 11.6% in processed foods, highlighting a significant lack of awareness about phosphate toxicity in chronic kidney disease (CKD) patients.

After learning about the risks of high phosphate consumption, 40.5% of students expressed a desire to reduce their intake of phosphate-rich fast foods and sodas, indicating a need for better education on dietary phosphate management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of awareness among future medical professionals about the risk of consuming hidden phosphate-containing processed food and drinks. Shutto, Y., Shimada, M., Kitajima, M., et al.[2021]

Most healthy adults in the U.S. consume nearly double the Recommended Dietary Allowance (RDA) of phosphate, which is set at 700 mg/day, leading to potential health risks.

Excessive phosphate intake is linked to serious health issues such as cardiovascular diseases, kidney diseases, and tumor formation, highlighting the need for better nutritional education and clearer labeling on food products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common Dietary Sources of Natural and Artificial Phosphate in Food. Miyamoto, KI., Oh, J., Razzaque, MS.[2022]

In a study of 10 patients with primary hyperparathyroidism, oral phosphate treatment significantly reduced levels of 1,25-dihydroxyvitamin D and calcium excretion, indicating a potential therapeutic effect on hypercalciuria and renal stone formation.

While phosphate therapy showed promise in managing symptoms, it also led to increased biochemical hyperparathyroidism, suggesting that the treatment's long-term impact on bone health and overall metabolic balance needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A detailed evaluation of oral phosphate therapy in selected patients with primary hyperparathyroidism. Broadus, AE., Magee, JS., Mallette, LE., et al.[2015]

A systematic screening of 3763 medications revealed that 12.5% contained phosphorus as an excipient, with the highest prevalence found in oral antidiabetic (23.8%) and antidepressant (19.2%) medications.

While the overall prevalence of phosphate-containing medications is low, calcium hydrogen phosphate, the most common form found, has a lower intestinal absorption rate compared to sodium phosphate, suggesting that the extra phosphate load from medications is generally minimal and mainly a concern in specific cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The extra-phosphate intestinal load from medications: is it a real concern? Cupisti, A., Moriconi, D., D'Alessandro, C., et al.[2018]

Sodium phosphate, commonly used for bowel cleansing, can lead to serious side effects such as hypocalcemia, hyperphosphatemia, and renal failure, as demonstrated in a case involving a 75-year-old woman.

The patient's hypocalcemic tetany and renal failure were linked to asymptomatic hypoparathyroidism, highlighting the importance of considering underlying health conditions when using sodium phosphate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptomatic hypocalcemia after sodium phosphate preparation in an adult with asymptomatic hypoparathyroidism. Niemeijer, ND., Rijk, MC., van Guldener, C.[2013]

Sodium phosphate is an effective bowel preparation agent that is generally safe and better tolerated by patients due to its smaller volume requirements.

However, there are significant risks associated with its use, particularly in patients with advanced age, impaired renal function, or colonic motility issues, as evidenced by six reported cases of severe electrolyte imbalances and life-threatening complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe hyperphosphataemia and associated electrolyte and metabolic derangement following the administration of sodium phosphate for bowel preparation. Tan, HL., Liew, QY., Loo, S., et al.[2022]

Regular consumption of ready-to-eat meals is linked to obesity and various health issues, including cardiovascular diseases and diabetes, due to their high calorie content and unhealthy additives.

Excessive intake of phosphate preservatives in processed foods can lead to phosphate toxicity, which may contribute to kidney disease and vascular problems, highlighting a need for better awareness among health professionals and the public.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity, Diabetes Mellitus, and Vascular Impediment as Consequences of Excess Processed Food Consumption. Sinha, S., Haque, M.[2022]

Elevated serum phosphorus is a significant risk factor for cardiovascular issues in dialysis patients, making dietary phosphorus restriction crucial for managing hyperphosphatemia.

The average daily phosphorus intake is around 1550 mg for males and 1000 mg for females, but this can be underestimated due to the addition of phosphates in processed foods, which can increase intake by up to 1 g/day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hidden sources of phosphorus in the typical American diet: does it matter in nephrology? Uribarri, J., Calvo, MS.[2022]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40065267/

Effectiveness of phosphate binders on mortality and ...

This study aimed to compare the effectiveness of NCBPBs, CBPBs, to no phosphate-binder (PB) on mortality and cardiovascular disease in Thai hyperphosphatemic ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3761537/

Effects of Sodium Phosphate Loading on Aerobic Power ...

The results indicate a significant (p < 0.05) increase in VO2max, VEmax, and O2/HR, due to sodium phosphate intake over 6 days. Also a significant (p < 0.05) ...

3.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2019/212121Orig1s000OtherR.pdf

212121Orig1s000 - accessdata.fda.gov

DIBASIC\SODIUM PHOSPHATE, DIBASIC, HEPTAHYDRATE\TRIBASIC CALCIUM ... MONOBASIC,SODIUM PHOSPHATE, DIBASIC\SODIUM PHOSPHATE,. MONOBASIC ...

4.

mdpi.com

mdpi.com/2072-6643/17/9/1587

Hyperphosphatemia in Kidney Failure: Pathophysiology ...

Abnormal phosphate metabolism is one of the major factors that is independently associated with vascular calcification and cardiovascular mortality in KF.

5.

academic.oup.com

academic.oup.com/ndt/article/28/12/2961/1832033

Phosphate control in end-stage renal disease - Oxford Academic

Data from observational studies demonstrate that an elevated serum phosphorus level is an independent risk factor for mortality, and that ...

6.

mayoclinic.org

mayoclinic.org/drugs-supplements/sodium-phosphate-dibasic-and-sodium-phosphate-monobasic-intravenous-route/description/drg-20529397

Sodium phosphate dibasic and sodium ...

Sodium phosphate dibasic and sodium phosphate monobasic combination injection is a phosphate replacement that is used to treat or prevent hypophosphatemia.

7.

sigmaaldrich.com

sigmaaldrich.com/sds/sigald/s9638?srsltid=AfmBOooCGj3SFPn-HhfAlgbRBYGnwHfm2MBSe0C3GF6FFwLkwu0Arw5T

Sodium phosphate monobasic monohydrate

OSHA: No component of this product present at levels greater than or equal to 0.1% is on OSHA's list of regulated carcinogens. Reproductive ...

8.

dailymed.nlm.nih.gov

dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e2fcc382-6fac-4438-ad02-ebc8528dd59a

Label: MONOBASIC SODIUM PHOSPHATE AND DIBASIC ...

Overdosage of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets may lead to severe electrolyte disturbances, including hyperphosphatemia, ...

9.

drugs.com

drugs.com/cons/sodium-phosphate-dibasic-and-sodium-phosphate-monobasic-intravenous.html

Uses for sodium phosphate dibasic and ...

Sodium phosphate dibasic and sodium phosphate monobasic combination injection is a phosphate replacement that is used to treat or prevent hypophosphatemia (low ...