Effect of Phosphorus Additives on the Metabolome in Healthy Adults

NCT03841786 | Completed

• 1 other identifier: IRB-300002442
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the effect of phosphorus supplementation on the human metabolome. The investigators will do so by conducting a cross-over study in healthy adults consuming a study diet (normal diet supplemented by neutral sodium phosphorus, 1 gram/day) for seven days and a control diet (normal diet supplemented by sodium and potassium chloride only) for seven days with a 28 day wash-out period in between. Untargeted metabolomic analyses will be done in serum samples obtained at the end of each diet period.

Conditions

Metabolic Syndrome; Insulin Sensitivity; Cardiovascular Diseases

Keywords

Metabolome; Phosphorus; Nutrition

Outcome Measures

Primary Outcomes (1)

• Untargeted Metabolomics

  Untargeted metabolomics will be the primary endpoint and will be performed on serum samples obtained for all participants at the end of each dietary period.

  7 days

Secondary Outcomes (1)

• Fibroblast growth factor 23 (FGF23)

  7 days

Study Arms (2)

Control diet

PLACEBO COMPARATOR

Participants will be asked to consume a normal diet supplemented with sodium chloride (sodium chloride tablets, USP, 1 gram; 3 tablets per day) and potassium chloride (Klor-Con, 8 mEq; 0.5 tablets per day) for 1 week.

Other: Control Diet

Phosphorus-supplemented study diet

EXPERIMENTAL

Participants will be instructed to consume a normal diet with supplemental phosphorus (K-Phos Neutral tablets, 250 mg; 4 tablets a day) for 1 week.

Other: Phosphorus-supplemented study diet

Interventions

Phosphorus-supplemented study diet OTHER

Participants will be instructed to consume a normal diet and will take a total of 1,000 mg of supplemental phosphorus per day in the form of neutral sodium phosphorus (K-Phos neutral®) for 1 week.

Phosphorus-supplemented study diet

Control Diet OTHER

Participants will be asked to consume a normal diet supplemented with sodium and potassium chloride tablets commensurate with the extra sodium and potassium content consumed during the study diet period for 1 week

Control diet

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• healthy volunteers, aged 18 - 45 years with normal kidney function (estimated glomerular filtration rate \> 60 ml/min/1.73m2).

You may not qualify if:

• abnormal urinalysis-presence of hematuria, proteinuria, or leukocyturia. pregnancy or breast-feeding
• Medical conditions impacting phosphate metabolism-primary hyperparathyroidism; gastrointestinal malabsorption disorders such as Crohn's Disease, ulcerative colitis, celiac disease, or liver dysfunction; hyper- or hypothyroidism; irregular menses for female subjects.
• Medications known to affect phosphorus metabolism- current use of phosphorus supplements, high-dose or activated vitamin D compounds, regular antacid or laxative use, anticonvulsants.
• Hyper- or hypophosphatemia (≥ 4.6 mg/dl or ≤ 2.5 mg/dl respectively), hyper- or hypocalcemia (≥ 10.6 or ≤ 8.5 mg/dl respectively), or severe anemia (hemoglobin \< 8 g/dl for women and \< 9 g/dl for men), hyperkalemia (potassium \> 5.0 mmol/L).

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

Related Publications (14)

• Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol. 2004 Aug;15(8):2208-18. doi: 10.1097/01.ASN.0000133041.27682.A2.

  PMID: 15284307 BACKGROUND

• Dhingra R, Sullivan LM, Fox CS, Wang TJ, D'Agostino RB Sr, Gaziano JM, Vasan RS. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med. 2007 May 14;167(9):879-85. doi: 10.1001/archinte.167.9.879.

  PMID: 17502528 BACKGROUND

• Foley RN, Collins AJ, Herzog CA, Ishani A, Kalra PA. Serum phosphate and left ventricular hypertrophy in young adults: the coronary artery risk development in young adults study. Kidney Blood Press Res. 2009;32(1):37-44. doi: 10.1159/000203348. Epub 2009 Feb 20.

  PMID: 19229116 BACKGROUND

• Ix JH, De Boer IH, Peralta CA, Adeney KL, Duprez DA, Jenny NS, Siscovick DS, Kestenbaum BR. Serum phosphorus concentrations and arterial stiffness among individuals with normal kidney function to moderate kidney disease in MESA. Clin J Am Soc Nephrol. 2009 Mar;4(3):609-15. doi: 10.2215/CJN.04100808. Epub 2009 Feb 11.

  PMID: 19211667 BACKGROUND

• Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, Sherrard DJ, Andress DL. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol. 2005 Feb;16(2):520-8. doi: 10.1681/ASN.2004070602. Epub 2004 Dec 22.

  PMID: 15615819 BACKGROUND

• Tonelli M, Sacks F, Pfeffer M, Gao Z, Curhan G; Cholesterol And Recurrent Events Trial Investigators. Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation. 2005 Oct 25;112(17):2627-33. doi: 10.1161/CIRCULATIONAHA.105.553198.

  PMID: 16246962 BACKGROUND

• Mathew S, Tustison KS, Sugatani T, Chaudhary LR, Rifas L, Hruska KA. The mechanism of phosphorus as a cardiovascular risk factor in CKD. J Am Soc Nephrol. 2008 Jun;19(6):1092-105. doi: 10.1681/ASN.2007070760. Epub 2008 Apr 16.

  PMID: 18417722 BACKGROUND

• Shuto E, Taketani Y, Tanaka R, Harada N, Isshiki M, Sato M, Nashiki K, Amo K, Yamamoto H, Higashi Y, Nakaya Y, Takeda E. Dietary phosphorus acutely impairs endothelial function. J Am Soc Nephrol. 2009 Jul;20(7):1504-12. doi: 10.1681/ASN.2008101106. Epub 2009 Apr 30.

  PMID: 19406976 BACKGROUND

• Adeney KL, Siscovick DS, Ix JH, Seliger SL, Shlipak MG, Jenny NS, Kestenbaum BR. Association of serum phosphate with vascular and valvular calcification in moderate CKD. J Am Soc Nephrol. 2009 Feb;20(2):381-7. doi: 10.1681/ASN.2008040349. Epub 2008 Dec 10.

  PMID: 19073826 BACKGROUND

• Saab G, Whooley MA, Schiller NB, Ix JH. Association of serum phosphorus with left ventricular mass in men and women with stable cardiovascular disease: data from the Heart and Soul Study. Am J Kidney Dis. 2010 Sep;56(3):496-505. doi: 10.1053/j.ajkd.2010.03.030. Epub 2010 Jun 26.

  PMID: 20580478 BACKGROUND

• Gutierrez OM. Fibroblast growth factor 23 and disordered vitamin D metabolism in chronic kidney disease: updating the "trade-off" hypothesis. Clin J Am Soc Nephrol. 2010 Sep;5(9):1710-6. doi: 10.2215/CJN.02640310. Epub 2010 May 27.

  PMID: 20507957 BACKGROUND

• Uribarri J. Phosphorus homeostasis in normal health and in chronic kidney disease patients with special emphasis on dietary phosphorus intake. Semin Dial. 2007 Jul-Aug;20(4):295-301. doi: 10.1111/j.1525-139X.2007.00309.x.

  PMID: 17635818 BACKGROUND

• Uribarri J, Calvo MS. Hidden sources of phosphorus in the typical American diet: does it matter in nephrology? Semin Dial. 2003 May-Jun;16(3):186-8. doi: 10.1046/j.1525-139x.2003.16037.x.

  PMID: 12753675 BACKGROUND

• Gutierrez OM, Luzuriaga-McPherson A, Lin Y, Gilbert LC, Ha SW, Beck GR Jr. Impact of Phosphorus-Based Food Additives on Bone and Mineral Metabolism. J Clin Endocrinol Metab. 2015 Nov;100(11):4264-71. doi: 10.1210/jc.2015-2279. Epub 2015 Aug 31.

  PMID: 26323022 BACKGROUND

MeSH Terms

Conditions

Metabolic Syndrome; Insulin Resistance; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Orlando Gutierrez, M.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary Investigator

Model Details: Eligible subjects will consume a phosphorus supplemented diet (study diet) and a sodium and potassium chloride supplemented diet (control diet), with cross-over to the other diet following a 24-day wash-out period. The order in which the diets are consumed will be randomly assigned.

Study Record Dates

• First Submitted: February 12, 2019
• First Posted: February 15, 2019
• Study Start: June 28, 2019
• Primary Completion: April 27, 2021
• Study Completion: September 15, 2022
• Last Updated: December 29, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)