Modification of stone risk profile in topiramate treated subjects

Study ID
Study00000121

Cancer Related
No

Healthy Volunteers
Yes

Study Sites

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

Principal Investigator
Naim Maalouf

Summary

aim 1
Design: 4 phase, double-blind randomized trial comparing the effects of oral potassium citrate vs. citric acid.
Subjects: 10 TPM-treated subjects
Procedures :
* Baseline evaluation: all subjects will be interviewed by a CTRC dietician and screened with a complete medical history. a physical examination, 24-hour urine, and fasting blood specimen will be collected.
* Test Materials: Study medications include potassium citrate, citric acid and placebo.
a) 4 capsules of citric acid (40 meq) + 2 capsules of placebo twice a day
b) 2 capsules of potassium citrate (20 meq) + 4 capsules of placebo twice a day
c) 2 capsules of potassium citrate (20 meq) + 4 capsules of citric acid (40 meq) twice a day
* Study Protocol: after the baseline evaluation, subjects will be randomized to the study medications for phases 2-4. each phase will be 6 days in duration, with a 2-day wash-out period in between. The subjects will then be randomized to another phase until all four are completed. on days 1-2 of each phase, subjects will be instructed by the CTRC dietitian to rigidly follow an instructed diet. on days 3-5, subjects will be provided a frozen metabolic diet of the same composition. 24-hour urine samples will be collected by the subjects on days 4 and 5. a fasting venous blood sample will be obtained on day 6.

aim 2
Design: 4 phase, double-blind randomized trial comparing the effects of different doses of oral citric acid.
Subjects: 10 TPM-treated subjects
Procedures:
* Baseline evaluation: all subjects will be interviewed by a CTRC dietician and screened with a complete medical history. a physical examination, a 24-hour urine, and fasting blood specimen will be collected.
* Test Materials: The study medications include citric acid and placebo.
a) 2 capsules of citric acid (20 meq) + 4 capsules of placebo twice a day
b) 4 capsules of citric acid (40 meq) + 2 capsules of placebo twice a day
c) 6 capsules of citric acid (60 meq) twice a day
* Study Protocol: after the baseline evaluation, the subjects will be randomized to the study medications for phases 2-4. each phase will be 6 days in duration, with a 2-day wash-out period in between. The subjects will then be randomized to another phase until all four are completed. on days 1-2 of each phase, subjects will be instructed by the CTRC dietitian to rigidly follow an instructed diet. on days 3-5, the subjects will be provided a frozen metabolic diet of the same composition. 24-hour urine samples will be collected by the subjects on days 4 and 5. a fasting venous blood sample will be obtained on day 6.

aims 3 and 4
Design: 3 phase, double-blind, randomized trial comparing the effects oral potassium citrate vs. citric acid on risk of calcium stone formation.
Subjects: 10 healthy, non-stone forming subjects (aim 3) and 10 calcium phosphate stone forming subjects (aim 4)
Procedures:
* Screening: all subjects will be interviewed by a CTRC dietician and screened with a complete medical history. a physical examination, a 24-hour urine, and fasting blood specimen will be collected.
* Test Materials: The study medications include citric acid, potassium citrate, and placebo.
a) 4 capsules of citric acid (40 meq) twice a day
b) 2 capsules of potassium citrate (20 meq) + 2 capsules of placebo twice a day
c) 4 capsules of placebo twice a day
* Study Protocol: Subjects will be randomized to the study medications for phases 1-3. each phase will be 6 days in duration, with a 2-day wash-out period in between. The subjects will then be randomized to another phase until all three phases are completed. on days 1-2 of each phase, subjects will be instructed by the CTRC dietitian to rigidly follow an instructed diet. on days 3-5, the subjects will be provided a frozen metabolic diet of the same composition. 24-hour urine samples will be collected by the subjects on days 4 and 5. a fasting venous blood sample will be obtained on day 6.

Participant Eligibility

Aims 1 & 2: Patients on TPM treatment for greater than or equal to 3 months, at a dose of 100 mg daily or greater, 21 years of age and greater, either gender, any race, with a BMI greater than 18.5 kg/m2.

Aim 3: Helathy, non-stone forming subject, age greater than 21 years of either gender, any race and BMI greater than 18.5 kg/m2

Aim 4: Calcium phosphate stone forming subject, age greater than 21 years of either gender, any race and BMI greater than 18.5 kg/m2