Antiepileptic Drugs and Osteoporotic Prevention Trial (ADOPT)

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.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Osteoporosis; Bone Loss; Fractures
• Intervention / Treatment: Drug: Risedronate; Drug: Placebo + Calcium and Vitamin D

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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02130
      • VA Boston Healthcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Risedronate; Active drug	Drug: Risedronate; 35 mgs/week + calcium and vit d; Other Names: Actonel
Placebo Comparator: Placebo + Calcium and Vitamin D; All patients both on placebo and active bisphosphonate to receive calcium and vitamin D	Drug: Placebo + Calcium and Vitamin D; sugar pill + calcium 1200mgs/day and vitamin d at least 800IU; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Vertebral Fractures	2 years

Collaborators and Investigators

• Sponsor: Boston VA Research Institute, Inc.
• Collaborators: Alliance for Better Bone Health; Procter and Gamble; VA Boston Healthcare System
• Investigators: Principal Investigator: Antonio A Lazzari, MD, VA Boston HCS; Principal Investigator: Phillip Dussault, Pharm D, VA Boston HCS; Principal Investigator: Manisha Thakore, MD, VA Boston HCS

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: March 25, 2009
• First Submitted That Met QC Criteria: March 25, 2009
• First Posted (Estimate): March 26, 2009

Study Record Updates

• Last Update Posted (Estimate): July 24, 2015
• Last Update Submitted That Met QC Criteria: July 23, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: osteoporosis; fracture; bone mineral density; antiepileptic drug; seizure; Prevention of bone loss; Prevention of osteoporosis; Prevention of Fractures
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Vitamin D; Calcium; Risedronic Acid
• Other Study ID Numbers: VABHS IRB#1889