Osteoporosis
Conditions
Keywords
Disorder of Bone Density and Structure, Unspecified, Weakening of the bone structure
Brief summary
This is a research study to determine the effects of functional electrical stimulation (FES) rowing and a drug called zoledronic acid in bone health. The investigators hoped to learn if zoledronic acid treatment will increase bone mineral density in persons with chronic spinal cord injury (SCI) who received it. The investigators also want to find out if zoledronic acid is safe for persons with SCI to take without causing too many side effects.
Detailed description
This research study was designed to determine the effects of functional electrical stimulation (FES) rowing and a drug called zoledronic acid in bone health in individuals who have suffered a spinal cord injury (SCI). The investigators hoped to learn if zoledronic acid treatment would increase bone mineral density in persons with chronic spinal cord injury. This was designed and conducted as a three center study with multiple investigators. The investigators also had a goal to find out if zoledronic acid is safe for persons with SCI without causing too many side effects. The Prime recipient of funding is Spaulding Rehabilitation Hospital (SRH). Dr. Leslie Morse is the Principal Investigator for the study, the coordination of the study was located at Spaulding Rehabilitation Hospital. Through a sub-award a research group from the Veterans Administration of Boston Healthcare System was contracted to conduct DXA scans, blood draws and zoledronic acid administration to support this study. Through another sub-award from SRH, another Investigator from Massachusetts General Hospital (MGH) participated conducting CT scans for the study. All adverse events related to this study were to be monitored and recorded by investigators at SRH. Seventy subjects age 18 years or older and wheelchair dependent at least 50% of the time because of an SCI were enrolled. Enrollment and initial screening for the study and follow up was performed at SRH. After enrollment the subjects were randomized to 1) FES-rowing alone or 2) FES-rowing plus a 1-time infusion of zoledronic acid. Following a variable period of strength training which was necessary for preparing quads and hamstrings for extended FES use, enrolled participants were planned to begin a regular rowing program for 12 months at the Cardiovascular Laboratory at the Spaulding Rehabilitation Hospital . DXA scans to measure bone mineral density were planned to be performed at the VA Boston Healthcare System-Jamaica Plain Campus (VABHS) three times during the study on all participants. In addition, 25 subjects in each arm of the study were planned to receive CT scans of their knees at MGH at the beginning and end of the study. Up to 20 subjects were to have an additional CT scan (at MGH) six months into rowing. Research blood samples were planned to be collected at VABHS five times during duration of the study and stored at the VA for further study of molecular markers of bone turnover. All participants were expected to be screened for renal function and calcium and vitamin D levels at the beginning and end of the study, with additional renal screening done before and after the zoledronic acid infusion. Calcium and vitamin D supplements were to be provided to each subject throughout the study. Those with insufficient vitamin D levels were to be provided additional repletion and planned to be periodically rechecked. Up to 15 male subjects were asked to have two echocardiograms at one of the SRH sites - one at the beginning of the study and the other halfway through the year-long rowing regimen.
Interventions
OTHERFES-Rowing
FES- Rowing Exercise
DRUGZoledronic acid
5 mg IV single dose
Sponsors
United States Department of Defense
Spaulding Rehabilitation Hospital
VA Boston Healthcare System
Massachusetts General Hospital
Antonio Lazzari
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* male and female SCI outpatients * women of child bearing age will be required to use an acceptable birth control method throughout the study * aged 18 - over the age of 40 * physician's cardiac clearance to exercise * who were at least age 14 at time of injury * who are at least 18 months post injury * who have a C4 spinal cord injury or lower
Exclusion criteria
* initial blood pressure higher than 140/90 * patients with orthostatic hypotension * an active grade 2 or greater pressure ulcers * lower extremity contractures * history of significant arrhythmias * coronary disease * diabetes * neurological or renal disease * cancer * other neurological disease (i.e. stroke, peripheral neuropathy, myopathy) * any implanted electronic device * active treatment for epilepsy * recent weight change * regular use of tobacco * family history of arrhythmia or sudden cardiac death * current use of cardioactive or antidepressant medications * current use of medications that may affect fracture risk including: * bisphosphonates * PTH and PTH analogs * androgenic steroids * estrogenic steroids * glucocorticoids * antiepileptics * lithium. * Any subject with a planned invasive dental procedure will be excluded. These criteria will be reviewed by telephone survey followed by a health exam where blood pressure will be assessed and a skin and neurological exam performed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement of Bone Mass as Measured by Sequential Evaluation of Bone Density and Bone Structure | 12 months | This work was designed to determine if FES-rowing plus Zoledronic acid is superior to FES-rowing alone reversing deterioration and weakening of the bones due to SCI and was planned to confirm the effects of FES-rowing in bone structure in patients not receiving Zoledronic Acid. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Validation of DXA Scanning in Patients With SCI | 12 months | This study has been designed to evaluate whether sequential DXA scanning of the distal femur and proximal femur is an appropriate clinical tool to monitor bone changes in response to either treatment. Evaluation of bone density by DXA was planned to be compared to CT scans of the distal femur and proximal tibia. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ZA Infusion Arm Thirty five subjects in each arm, age 18 years or older and wheelchair dependent at least 50% of the time because of an SCI were enrolled. | 35 |
| Rowing Arm Thirty five subjects, in each arm age 18 years or older and wheelchair dependent at least 50% of the time because of an SCI were enrolled. | 35 |
| Total | 70 |
Baseline characteristics
| Characteristic | Rowing Arm | ZA Infusion Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 35 Participants | 70 Participants |
| Age, Continuous | 39.0 Years | 37.2 Years | 38.1 Years |
| Region of Enrollment United States | 35 participants | 35 participants | 70 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 32 Participants | 32 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 26 | 15 / 19 |
| serious Total, serious adverse events | 6 / 26 | 6 / 19 |
Outcome results
Primary
Improvement of Bone Mass as Measured by Sequential Evaluation of Bone Density and Bone Structure
This work was designed to determine if FES-rowing plus Zoledronic acid is superior to FES-rowing alone reversing deterioration and weakening of the bones due to SCI and was planned to confirm the effects of FES-rowing in bone structure in patients not receiving Zoledronic Acid.
Time frame: 12 months
Population: Data was never analyzed because the study was closed by the VABHS IRB. Full dataset is unavailable for analysis.
Secondary
Validation of DXA Scanning in Patients With SCI
This study has been designed to evaluate whether sequential DXA scanning of the distal femur and proximal femur is an appropriate clinical tool to monitor bone changes in response to either treatment. Evaluation of bone density by DXA was planned to be compared to CT scans of the distal femur and proximal tibia.
Time frame: 12 months
Population: Dataset unavailable for analysis to VABHS study team. The study was closed by the VABHS IRB.