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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Korea, Ltd., Korea
ClinicalTrials.gov Identifier:
NCT01030094
First received: December 10, 2009
Last updated: June 25, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Seizures
Convulsions
Epilepsy
Osteopenia
Osteoporosis
Drug: Topiramate
Drug: Carbamazepine
Drug: Valproic acid
Drug: Normal control
Phase 4

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Janssen Korea, Ltd., Korea:

Primary Outcome Measures:
  • Absolute Concentration of Calcium in Serum and Random Urine [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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.

  • Absolute Concentration of 25-hydroxy Vitamin D, Osteocalcin, Carboxy-terminal Telopeptide of type 1 collagen (CTx) and Somatomedin-C (IGF-1) in Serum [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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.

  • Absolute Concentration of 1-alpha 25-dihydroxyvitamin D-3, Parathyroid Hormone (PTH) in Serum [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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.

  • Absolute Concentration of Bone-specific Alkaline Phosphatase (BSAP) in Serum [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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.

  • Absolute Concentration of Bicarbonate in Serum [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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.

  • Absolute Concentration of Calcium in Urine in 24 Hours [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Absolute concentration of calcium in urine will be examined by urine test.


Secondary Outcome Measures:
  • Spine, Total hip and Femoral Neck Z-Score [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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 T-score [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Osteopenia and Osteoporosis Based on Spine Z-score [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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.

  • Absolute Concentration of Phosphorus and Creatinine in Random Urine [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Absolute concentration of phosphorus and creatinine in urine will be examined by urine test.

  • Absolute concentration of Sodium in Random Urine [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Absolute concentration of sodium in urine will be examined by urine test.

  • Absolute Concentration of Phosphorus and Creatinine in 24 Hour Urine [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Absolute concentration of phosphorus and creatinine in 24 hour urine will be examined by urine test.

  • Absolute concentration of Sodium in 24 Hour Urine [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Absolute concentration of sodium in 24 hour urine will be examined by urine test.


Enrollment: 140
Study Start Date: February 2007
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

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

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01030094

Sponsors and Collaborators
Janssen Korea, Ltd., Korea
Investigators
Study Director: Janssen Korea, Ltd. Clinical Trial Janssen Korea, Ltd., Korea
  More Information

No publications provided

Responsible Party: Janssen Korea, Ltd., Korea
ClinicalTrials.gov Identifier: NCT01030094     History of Changes
Other Study ID Numbers: CR015856, TOP-KOR-31
Study First Received: December 10, 2009
Last Updated: June 25, 2013
Health Authority: Korea: Food and Drug Administration

Keywords provided by Janssen Korea, Ltd., Korea:
Topiramate
Carbamazepine
Valproic acid
Epilepsy
Bone mineral density
Monotherapy

Additional relevant MeSH terms:
Epilepsy
Osteoporosis
Bone Diseases
Bone Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Musculoskeletal Diseases
Nervous System Diseases
Carbamazepine
Topiramate
Valproic Acid
Analgesics
Analgesics, Non-Narcotic
Anti-Obesity Agents
Anticonvulsants
Antimanic Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
GABA Agents
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Psychotropic Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014