Comparison of Potassium Citrate and Citric Acid Supplementation for Modification of Stone Risk Profile, and Assessment of Calcium Metabolism and Bone Turnover in Topiramate Treated Subjects

Summary

Screening: Up to 50 Adult and 50 Pediatric TPM-treated subjects will be screened with blood and urine tests. Subjects will be contacted via telephone and asked to answer questions related to their medical history. Adult subjects give verbal consent to collect a 24-hour urine sample and have blood drawn. Children – The parents of pediatric subjects will be approached during a regularly scheduled clinic visits. If willing, they will sign the consent and HIPAA forms. Subjects will be paid $25 if they complete the study.

Aim 1: 12 healthy adult volunteers will be enrolled. Subjects will be screened by a dietician with a complete medical history, 24-hour urine, and fasting blood specimen. This is a double-blind crossover study with 2 phases: Subjects will be randomized to either potassium citrate or citric acid in Phase 1 and assigned to the opposite treatment in Phase 2. Each phase will be separated by a 7-day period during which a study medication will not be given. The study medications include liquid potassium citrate and citric acid. The same dosage will be used for both supplements. During the study, two 24-hour urine and two blood specimens will be collected. Subjects will receive a metabolic diet prepared by the CTRC dietary staff. Subjects will be paid $75 for each phase that they complete.

Aim 2: 15 subjects will be enrolled in the outpatient and 15 subjects will be enrolled in the inpatient portion of the study. A physical examination, a 24-hour urine, and fasting blood specimen will be collected. Subjects will be evaluated in three separate inpatient admissions: at baseline (phase 1), at the end of phase 2 (potassium citrate administration), and the end of phase 3 (citric acid administration). A urine pregnancy test will be done prior to starting each phase of the study. Subjects will receive a metabolic diet prepared by the CTRC dietary staff. Two 24-hour urine and two fasting venous blood samples will be collected. The subjects will be paid $75 for each evaluation that they complete. Pilot Study: *Pilot study was closed to enrollment via a MOD submitted on 1/14/2010*

Aim 3: 35 adult subjects will be enrolled in the study. A physical examination, a 24-hour urine, and fasting blood specimen will be collected for screening. Subjects will be evaluated at the inpatient CTRC at baseline (before initiation of TPM therapy), 12 months and 24 months. Subjects will be instructed to achieve an optimal intake of calcium and vitamin D throughout the study. Subjects will receive a metabolic diet prepared by the CTRC dietary staff. A 2-hour urine sample, two 24-hour urine samples, and 2 fasting blood samples will be collected. Glomerular filtration rate (GFR) will be determined by iothalamate clearance. Fractional intestinal calcium absorption will be determined by dual isotope technique. A DXA scan will be performed at baseline, 12 month, and 24 months. Bone strength will be assessed by heel UCR at baseline, 12 months, and 24 months. 3 months after the baseline evaluation, subjects will have an outpatient visit at the CTRC where they will obtain a 24-hour urine collection. Subjects will be paid $100 for each inpatient evaluation that they complete and $25 for the outpatient evaluation.

Aim 4: 20 adult subjects will be enrolled. Subjects will be screened by a dietitian for a complete history, physical examination, 24-hour urine, and fasting blood specimen. They will be evaluated in two separate inpatient admissions: baseline and at t

Participant Eligibility

Screening: 50 Adult and 50 pediatric subjects treated with TPM for at least one month prior to the study.

Aim 1: Twelve healthy volunteers, 21 years of age and greater, either gender, any race, with a body mass index (BMI) greater than 18.5 kg/m2 (kilograms/meters2).

Aim 2: Twelve 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: Thirty-five patients who are anticipated to be on long-term use of TPM as prescribed by subjects’ neurologist, age greater than 21 years (both genders, pre-menopausal and postmenopausal women), any race, with a BMI greater than 18.5 kg/m2. Spanish speaking subjects will be eligible for this study.

Aim 4: 20 subjects older than 21 of either gender, any race and BMI greater than 18.5 kg/m2 prior to treatment with TPM will participate in this aim.