Bone Loss, Epilepsy, Fractures, Osteoporosis
Conditions
Keywords
osteoporosis, bone mineral density, fracture, antiepileptic drug, seizure, Prevention of bone loss, Prevention of osteoporosis, Prevention of Fractures
Brief summary
Study Design: (e.g., Controlled, Double-Blind, Randomized, Parallel): Randomized, double-blind, placebo controlled of a bisphosphonate in the prevention of bone loss associated with the use of antiepileptic drugs.
Detailed description
The study is planned to last two years. You will be required to make a total of 6 visits to the clinic during this two year study period. At the first visit, 12 months and, approximately 24 months, you will have a bone mineral density test (BMD) of your hip and spine. A BMD is similar to having an x-ray and is a test that measures the amount of bone. This test takes approximately 15 minutes. Radiation exposure during this test is very low. It has been estimated that the total radiation exposure from a bone mineral density measurement is lower than that of a dental x-ray. At each follow up visit an assessment will be made for side effects and whether or not you followed the prescribed treatment. Initially, information collected will include height, weight, seizure history and seizure medication history, other medical conditions, bone and muscle symptoms you currently have, dietary calcium intake, and exercise. Blood will be drawn at the initial and 5 follow-up visits. The purpose of this is to test your blood for organ function, calcium levels, vitamin D levels and levels of markers that show high bone turnover. Also at each visit your height and weight will be checked and you will be asked questions regarding side effects, adherence to treatment and quality of life. When you agree to participate, you will be randomized to either risedronate 35mg tablet (Actonel ®) or placebo (a fake pill) to take once a week. Randomization is a process in which you will have an equal chance (like the flip of a coin) to be assigned to either risedronate (Actonel ®) or placebo. A computer program will determine your treatment assignment. Also during the study you will be provided with calcium and vitamin D tablets to take either two or three times each day depending on your dietary calcium intake. At the first visit you will be assessed for changeable risk factors for osteoporosis. These include smoking, alcohol consumption, and lack of physical activity, poor nutrition and lack of vitamin intake. Also, blood will be drawn to see if you have a low male hormone. If you are found to have low male hormone, you will be referred to your primary care provider. If you have low male hormone levels, you will be eligible to participate in the study if testosterone replacement has been offered to you and you have declined treatment. If you decide to be treated with testosterone you are not eligible to participate in this study. Education will be provided on exercises for bones. If you smoke, you will be counseled on quitting although quitting is not a requirement to participate in the study. If you drink a lot of alcohol you will be counseled on reducing your intake and offered help. Reducing or quitting alcohol is not a requirement for your participation in this study. You can also meet with a registered dietician for nutritional counseling.
Interventions
DRUGRisedronate
35 mgs/week + calcium and vit d
DRUGPlacebo + Calcium and Vitamin D
sugar pill + calcium 1200mgs/day and vitamin d at least 800IU
Sponsors
Procter and Gamble
Alliance for Better Bone Health
VA Boston Healthcare System
Boston VA Research Institute, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Male gender * Epilepsy * Anti-epileptic drug treatment with phenytoin, or phenobarbital or valproate sodium * Normal renal function and normal Vitamin D and calcium levels
Exclusion criteria
* Female gender * Organ transplant * Use of oral glucocorticoids * Renal insufficiency (eGFR \< 30ml/min) * Severe swallowing disorder * Severe esophagitis * Patients taking sodium valproate for reasons other than epilepsy * Previous treatment with osteoporosis drugs such as bisphosphonates, calcitonin or PTH analog
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Bone Mineral Density | 2 years | Patients with a T-Score of \> -2.5 were randomized into two possible arms. A bisphosphonate group received 35mg risedronate weekly while another group received an identical placebo tablet weekly. Both groups received supplemental calcium and vitamin D. Enrolled patients had bone density measurements of bilateral proximal femur, A-P lumbar spine, total body, forearm and L-P spine. All measurements were performed on a GE Lunar Bone Densitometer (iDXA) instrument. Measurements of 25-hydroxy vitamin D, NTX , serum calcium and blood chemistries occurred at scheduled intervals. |
Secondary
| Measure | Time frame |
|---|---|
| Vertebral Fractures | 2 years |
Countries
United States
Participant flow
Recruitment details
80 veterans with epilepsy who were treated with phenobarbital, phenytoin, carbamazepine and sodium valproate.
Pre-assignment details
80 epileptic patients who have been on phenytoin, phenobarbital, carbamazepine or sodium divalproex for at least 2 years were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Risedronate Active drug participants received calcium and vitamin D supplementation in addition to 35 mgs of risedronate tablet weekly | 40 |
| Placebo Sugar Pill Placebo participants received calcium and vitamin D supplementation in addition to a placebo tablet identical to risedronate tablet weekly | 40 |
| Total | 80 |
Baseline characteristics
| Characteristic | Risedronate | Placebo Sugar Pill | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 11 Participants | 30 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 29 Participants | 50 Participants |
| Age, Continuous | 63 years STANDARD_DEVIATION 13 | 58 years STANDARD_DEVIATION 13 | 61 years STANDARD_DEVIATION 13 |
| Baseline Vitamin D Level | 29.1 ng/ml STANDARD_DEVIATION 19 | 29.3 ng/ml STANDARD_DEVIATION 16 | 29.2 ng/ml STANDARD_DEVIATION 17.5 |
| Current Smokers Non Smokers | 11 participants | 12 participants | 23 participants |
| Current Smokers Smokers | 29 participants | 28 participants | 57 participants |
| Previous Vertebral Fractures No veterbral fractures | 25 participants | 31 participants | 56 participants |
| Previous Vertebral Fractures Previous vertebral fractures | 15 participants | 9 participants | 24 participants |
| Region of Enrollment United States | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 40 Participants | 40 Participants | 80 Participants |
| Type of seizures Grand Mal Seizures | 19 participants | 22 participants | 41 participants |
| Type of seizures Other types of seizures | 21 participants | 18 participants | 39 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 40 | 0 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
Primary
Changes in Bone Mineral Density
Patients with a T-Score of \> -2.5 were randomized into two possible arms. A bisphosphonate group received 35mg risedronate weekly while another group received an identical placebo tablet weekly. Both groups received supplemental calcium and vitamin D. Enrolled patients had bone density measurements of bilateral proximal femur, A-P lumbar spine, total body, forearm and L-P spine. All measurements were performed on a GE Lunar Bone Densitometer (iDXA) instrument. Measurements of 25-hydroxy vitamin D, NTX , serum calcium and blood chemistries occurred at scheduled intervals.
Time frame: 2 years
Population: The study design involved 80 veterans with epilepsy who were treated with phenobarbital, phenytoin, carbamazepine and sodium valproate. This is a prospective study in which 80 patients who have been on phenytoin, phenobarbital, carbamazepine or sodium divalproex for at least 2 years were enrolled.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Risedronate | Changes in Bone Mineral Density | Bilateral Proximal Femora | 1.025 g/cm2 | Standard Deviation 0.111 |
| Risedronate | Changes in Bone Mineral Density | L1-L4 AP Spine | 1.332 g/cm2 | Standard Deviation 0.111 |
| Risedronate | Changes in Bone Mineral Density | Total Body BMD | 1.205 g/cm2 | Standard Deviation 0.096 |
| Placebo Sugar Pill | Changes in Bone Mineral Density | Bilateral Proximal Femora | 0.999 g/cm2 | Standard Deviation 0.174 |
| Placebo Sugar Pill | Changes in Bone Mineral Density | L1-L4 AP Spine | 1.245 g/cm2 | Standard Deviation 0.154 |
| Placebo Sugar Pill | Changes in Bone Mineral Density | Total Body BMD | 1.192 g/cm2 | Standard Deviation 0.127 |
Secondary
Vertebral Fractures
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Risedronate | Vertebral Fractures | 0 Vertebral Fractures |
| Placebo Sugar Pill | Vertebral Fractures | 5 Vertebral Fractures |
p-value: 0.0229Fisher Exact