A Cross-sectional Study to Investigate the Effect of Topiramate on Bone and Mineral Metabolism in Female Participants With Epilepsy

A Cross-sectional, Comparative, Multi-center Study to Investigate the Effect of Topiramate Monotherapy on Markers of Bone Mineral Metabolism and Bone Mineral Density in Premenopausal Women With Epilepsy

The purpose of this study is to investigate the influence of topiramate monotherapy on the bone and mineral metabolism markers, and bone density (the amount of mineral per square centimeter of bone ) in female participants with epilepsy (seizure disorder), before menopause (time in life when a woman stops having a menstrual period), as compared with healthy participants and comparative group received either carbamazepine or valproic acid monotherapy for at least last one year.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Seizures; Osteoporosis; Osteopenia; Convulsions
• Intervention / Treatment: Drug: Topiramate; Drug: Carbamazepine; Drug: Valproic acid; Drug: Normal control

Detailed Description

This is a cross-sectional (observations or measurements made at a single point in time, usually at participant enrollment), multi-center (conducted in more than one center), and comparative study of topiramate monotherapy in female participants with epilepsy. Female participants must have received either topiramate, carbamazepine, or valproic acid monotherapy for more than one year for the treatment of epilepsy. Blood samples will be obtained from fasting participants to investigate the effect of study drug on the bone and mineral metabolism markers, and bone density compared to healthy participants and comparative group (carbamazepine and valproic acid monotherapy). Bone mineral density will be measured from the participants' lumbar spine or femur. A survey of food intake and physical activity for the participants will be performed using a standardized validated detailed questionnaire. The post-study visit (or follow up phone contact) will be performed for the occurrence of serious adverse events (SAE) for safety evaluation. Participants' safety will be monitored throughout the study.

• Study Type: Observational
• Enrollment (Actual): 140

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Female participants with epilepsy who are receiving topiramate, carbamazepine or valproic acid monotherapy for more than one year.

Description

Inclusion Criteria:

• Participants who agree to participate in this study
• Female epileptic participants
• Participants who are receiving topiramate, carbamazepine or valproic acid monotherapy for more than one year
• Participants who are using proper contraceptive method (s) or have a negative pregnancy test result

Exclusion Criteria:

• Participants with a motor function disorder
• Participants with a disease which affects their skeleton including primary hyperparathyroidism, Paget's disease, multiple myeloma, liver and kidney disorder, thyroid disease, malabsorption disorder, diabetes, and malignancies
• Participants who have taken within last one year, or are currently taking a drug which affects the bone and mineral metabolism such as vitamin D, calcium, anabolic steroids, bisphosphonates, calcitonin, glucocorticoids, and diuretics
• Voluntary or surgical postmenopausal participants
• Participants with amenorrhea for more than 6 months

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Topiramate; Female participants with epilepsy will be observed, who were receiving topiramate for more than one year.	Drug: Topiramate; This is an observational study. Female participants with epilepsy will be observed, who were receiving topiramate for more than one year.
Carbamazepine; Female participants with epilepsy will be observed, who were receiving carbamazepine for more than one year.	Drug: Carbamazepine; This is an observational study. Female participants with epilepsy will be observed, who were receiving carbamazepine for more than one year.
Valproic acid; Female participants with epilepsy will be observed, who were receiving valproic acid for more than one year.	Drug: Valproic acid; This is an observational study. Female participants with epilepsy will be observed, who were receiving valproic acid for more than one year.
Normal Control; Healthy female participants will be observed in Normal control group.	Drug: Normal control; This is an observational study. Healthy female participants will be observed in Normal control group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Concentration of Calcium in Serum and Random Urine	Bone and mineral metabolic marker represents the structure, cyclical metabolism, and hormone regulation of bone. Urinary calcium is one of the indicators of bone resorption (bone loss due to osteoclastic activity). Absolute concentration of calcium in serum and random urine will be assessed.	24 hours
Absolute Concentration of 25-hydroxy Vitamin D, Osteocalcin, Carboxy-terminal Telopeptide of type 1 collagen (CTx) and Somatomedin-C (IGF-1) in Serum	Osteocalcin is a vitamin K-dependent calcium-binding protein synthesized by osteoblasts and found primarily in bones. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. CTx is marker for bone resorption (bone loss due to osteoclastic activity). IGF-1 has growth-regulating, insulin-like, and mitogenic activities. Absolute concentration of 25-hydroxy vitamin D, osteocalcin, carboxy-terminal telopeptide of type 1 collagen (CTx) and somatomedin-C (IGF-1) in serum will be assessed.	24 hours
Absolute Concentration of 1-alpha 25-dihydroxyvitamin D-3, Parathyroid Hormone (PTH) in Serum	Bone and mineral metabolic marker represents the structure, cyclical metabolism, and hormone regulation of bone. 1-alpha 25-dihydroxyvitamin D-3 (vitamin D-3) and Parathyroid hormone (PTH) were assessed. The PTH maintains intracellular calcium levels in the body.	24 hours
Absolute Concentration of Bone-specific Alkaline Phosphatase (BSAP) in Serum	Bone and mineral metabolic marker represents the structure, cyclical metabolism, and hormone regulation of bone. Bone-specific alkaline phosphatase (BSAP) reflects formation of organic matrix in bone. Absolute concentration of BSAP in Serum will be assessed.	24 hours
Absolute Concentration of Bicarbonate in Serum	Bicarbonate levels in the blood are an index of the alkali reserve or buffering capacity. Difference in Bicarbonate level between topiramate, carbamazepine and valproic acid monotherapy groups will be assessed.	24 hours
Absolute Concentration of Calcium in Urine in 24 Hours	Absolute concentration of calcium in urine will be examined by urine test.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spine, Total hip and Femoral Neck Z-Score	Z-score is number of standard deviations a participant's bone mineral density (BMD) differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values". Z-score will be evaluated for spine, hip and femoral neck.	24 hours
Percentage of Participants With Osteopenia and Osteoporosis Based on Spine T-score	Osteoporosis means reduction of bone mass without alteration in the composition of bone, leading to fractures. Osteopenia is a metabolic bone disease. The T-score is a radiographic diagnosis that compares bone mineral density (BMD) to that of a "normal, healthy, 30-year-old female". The lower the T-score, the lower the BMD. A T-score of +1 to -1 is normal. A T-score decrease of -1 indicates a 10%-15% decrease in BMD. Percentage of participants with osteopenia and osteoporosis based on spine T-score will be assessed.	24 hours
Percentage of Participants With Osteopenia and Osteoporosis Based on Spine Z-score	Osteoporosis means reduction of bone mass without alteration in the composition of bone, leading to fractures. Osteopenia is a metabolic bone disease. The Z-score is number of standard deviations a participant's bone mineral density (BMD) differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are "best values" and negative values are "worst values". Z-score will be evaluated for spine, hip and femoral neck. Percentage of participants with osteopenia and osteoporosis based on spine Z-score will be assessed.	24 hours
Absolute Concentration of Phosphorus and Creatinine in Random Urine	Absolute concentration of phosphorus and creatinine in urine will be examined by urine test.	24 hours
Absolute concentration of Sodium in Random Urine	Absolute concentration of sodium in urine will be examined by urine test.	24 hours
Absolute Concentration of Phosphorus and Creatinine in 24 Hour Urine	Absolute concentration of phosphorus and creatinine in 24 hour urine will be examined by urine test.	24 hours
Absolute concentration of Sodium in 24 Hour Urine	Absolute concentration of sodium in 24 hour urine will be examined by urine test.	24 hours

Collaborators and Investigators

• Sponsor: Janssen Korea, Ltd., Korea
• Investigators: Study Director: Janssen Korea, Ltd. Clinical Trial, Janssen Korea, Ltd., Korea

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: December 10, 2009
• First Submitted That Met QC Criteria: December 10, 2009
• First Posted (Estimate): December 11, 2009

Study Record Updates

• Last Update Posted (Estimate): June 26, 2013
• Last Update Submitted That Met QC Criteria: June 25, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Epilepsy; Bone mineral density; Monotherapy; Carbamazepine; Topiramate; Valproic acid
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Bone Diseases; Epilepsy; Seizures; Osteoporosis; Bone Diseases, Metabolic; Hypoglycemic Agents; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; GABA Agents; Anticonvulsants; Sodium Channel Blockers; Antimanic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Valproic Acid; Carbamazepine; Topiramate
• Other Study ID Numbers: CR015856; TOP-KOR-31