Regulation of Renal Calcium Transport by Acid-Base and Magnesium

Study ID
Study00000118

Cancer Related
No

Healthy Volunteers
Yes

Study Sites

Contact
Ashlei Johnson-Wilder
214-648-0394
ashlei.johnson@utsouthwestern.edu

Principal Investigator
Naim Maalouf

Summary

Study Design: This is a double-blind, placebo controlled, crossover study where subjects will undergo four phases: a) Low upH + Low uMg Phase, B) High upH + Low uMg Phase, C) Low upH + High uMg Phase, and D) High upH + High uMg Phase.

Study Subjects: 20 normal healthy subjects will be recruited and screened with a 24-hr urine collection, pregnancy test (in women of child-bearing age), and fasting blood (~ 2 teaspoons) studies for SMa-24 and CBC to evaluate for any exclusion criteria prior to enrollment into this study.

Study Procedures: The order of the four phases to be studied will be randomized by a biostatistician in a simple randomization scheme of blocks of 4. each of the four randomized phases will be 8 days in duration, during which subjects will take the prescribed study medications. a washout period of 1 week will be imposed between phases. The entire study will last 7 weeks. During the first 2 days of each phase, subjects will be instructed to adhere at home to a diet with a daily composition of 400 mg calcium, 100 meq sodium and 60 meq potassium and 3 liters of total fluids per day. on day 2 subjects will pick up a frozen diet from the Clinical and Translational Research Center (CTRC) to eat at home on days 3, 4 and 5. on the morning of day 6 subjects will be admitted to the inpatient CTRC and will be kept on a constant metabolic diet of the same composition provided by the CTRC for the last 2 days of each phase.

Study medications: upH will be effectively manipulated by either ammonium chloride or potassium citrate. High upH will be achieved by the provision of potassium citrate. Potassium chloride will be used as a control to potassium chloride. ammonium chloride is a well accepted means of delivering an acid load and lowering upH. To raise uMg, magnesium lactate will be used. Test drugs will be prepared by a compounding pharmacy.
General laboratory tests: on the morning of days 7 and 8 of each phase, a fasting venous blood will be obtained for the measurement of serum electrolytes, magnesium, calcium, albumin, and creatinine. approximately 2 teaspoons of blood will be drawn on each of these days. on days 6 and 7, a 24-hour urine sample will be obtained for pH, magnesium, calcium, oxalate, phosphorus, potassium, sodium, ammonium, chloride, sulfate, uric acid, creatinine and total volume. From these values, urinary relative saturation of calcium oxalate and brushite will be calculated by using the computer programs equil 2 (as relative supersaturation ratio, RSR) and JeSS (as supersaturation index, Si). The physicochemical studies of urine will include assessment of CPR (concentration product ratio), the empirically-derived measure of urinary saturation of calcium oxalate or brushite, based on dissolution or growth of added solid phase. Crystal growth is a newly developed method that will directly estimate the crystal growth of Caox and brushite seed.

alternate outpatient Study: Those subjects unwilling to participate as an inpatient will be offered the chance to participate as an outpatient. Subjects will eat an instructed diet on days 1-2, and will pick up a frozen diet from the CTRC kitchen to be eaten at home on days 3-7. Subjects will return to the CTRC or Mineral Metabolism outpatient clinic on days 7 and 8 to return their 24-hour urine collections and have their blood drawn. Tests will be performed as described above.

Participant Eligibility

Up to 20 healthy patients greater than 21 years of age, of either gender and of any race or ethnicity will be included in the study.