Elucidation of the Role of Calcium Sensor in Absorptive Hypercalciuria

Study ID
STU 012014-024

Cancer Related
No

Healthy Volunteers
Yes

Study Sites

  • CTRC Inpatient
  • CTRC Outpatient
  • Children’s Medical Center (Dallas, Plano, Southlake)
  • Parkland Health & Hospital System
  • UT Southwestern Ambulatory Services
  • UT Southwestern-Other

Contact
Sudeepa Bhattacharya
214/648-0395
Sudeepa.Bhattacharya@UTSouthwestern.edu

Principal Investigator
Khashayar Sakhaee, M.D.

Summary

Study Design
aim 1: Subjects will participate in three phases of study in the following order: Baseline, acute phase (single dose of Sensipar 60mg), and chronic phase (Sensipar 30mg bid for 16days). The second phase will commence immediately after the completion of the first phase. Phase 3 will commence immediately after the completion of phase 2.
aim 2 Subjects will participate in three phases of study including: aaaxsupplemented diet phase, mixture of aa-supplemented diet phase, and placebo-supplemented phase. The order of the phases will be random. each phase will last 5 days, and a 14-day washout will commence immediately after the completion of the first phase, followed by phase 2. Phase 3 will commence immediately after the completion of the phase 2 washout..
Study Protocol
aim 1: During the Baseline Phase, patients will follow an instructed diet at home for days 1 and 2. on days 3-4, they will be kept on a constant metabolic diet with a daily composition of 400mg of calcium, 800mg phosphorus, 100meq sodium, 50meq potassium, normal oxalate intake (~200mg/day), and 3 liters total fluids. on the evening of day 2 (4pm), subjects will be admitted to the CRu for metabolic study. They will have a metabolic dinner at 5pm and will fast except for distilled water load after the evening meal. They will have 300cc distilled water at 8pm and again at 11pm. at 6am on day 3, they will empty their bladder and discard the urine. They will then be given 600cc of distilled water to start a fasting 2hr urine collection until 8am for total volume, pH, calcium, phosphorus and creatinine. at 8am a baseline fasting blood will be collected. after the blood draw, fractional intestinal calcium absorption will be measured by dual isotope technique. Dual isotope technique, involves using 2 stable isotopes of calcium, one given orally and the other administered intravenously. isotopes used depend on availability from the supplier (Trace Sciences, Toronto Ca.) and pricing. Currently Ca42 is used for the iV dose and Ca46 for the oral. Doses are determined first by concentration as determined by Dr. Steve abrams lab at Baylor Houston. Doses are roughly 1 gram by weight and are increased 25% for those subjects over 80kg and 50% for those over 100kg. The oral isotope will be given with 100 mg of calcium in 90cc of ensure containing 100mg elemental calcium, followed by 50cc of distilled water to rinse. The patient will be nPo for 4 hours following the dual isotope procedure. Following the stable isotope administration, a 24-hr urine will be collected. urine samples will be measured for stable isotope by mass spectroscopy at Baylor College of Medicine, Houston, TX. on day 4, urine will be collected in a 24-hr pool. Fasting venous blood sample will be obtained at 8am. Subjects will be discharged on the morning of day 5.
acute Drug Phase
Same as baseline phase, with single dose of Sensipar 60mg with oral isotope on day 17.
Chronic Drug Phase
Subjects will take Sensipar 30mg BiD for a total of 15 days.
on the 31st day, they will undergo the same study procedures as Baseline phase.
aim 2: each subject will be studied during three 5-day phases separated by 14-day washout. The 3 experimental diets will be provided in random order. The normal-protein diet (0.8 g protein/kg BW) will consist of 800 mg (20 mmol) calcium, 800 mg phosphorus, 100 mmol sodium and 2.5 liters of total fluid daily. on days 1 through 4, the supplemental amino acids will be divided among the 3 meals in amounts proportional to the protein content of each meal, with the amount of aaa and mixed aa added to the low-protein diet adjusted to increase protein intake from normal (0.8 g/kg/day) to high (1.2 g/kg/day). on days 4 and 5, subjects will be admitted to the inpatient CRu to collect 24-hr urine and fasting blood at 8 aM. Serum concentration of aaa will be measured in a fasting state (8 aM) and post-prandially (at 4 PM). Subjects will be discharged the morning of day 6.

Participant Eligibility

Aim 1:
Recruited for the study will be three hypercalciuric patients with kidney stones and three normal participants without stones between 21-70 years of age, of either gender and any ethnicity. Kidney stone forming subjects will be designated as severely hypercalciuric with urinary calcium >= 300mg/day.

Aim 2:
Recruited for the study will be three hypercalciuric patients with kidney stones and three normal participants without stones between 21-70 years of age, of either gender and any ethnicity. Kidney stone forming subjects will be designated as severely hypercalciuric with urinary calcium >= 300mg/day.