FES-Rowing Versus Zoledronic Acid to Improve Bone Health in Spinal Cord Injury (SCI)

Phase 2

Terminated

Conditions: Osteoporosis

Interventions: Other: FES-Rowing
Drug: Zoledronic acid

Registration Number: NCT01426555

Lead Sponsor: Antonio Lazzari

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 70

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FES Rowing	FES-Rowing	Group 1 - FES-Rowing Exercise for entire study period
FES Rowing + Zoledronic acid	FES-Rowing	Group 2 - FES-Rowing Exercise for entire study period plus Zoledronic Acid 5mg administered by i.v. infusion one-time at the end of observation period
FES Rowing + Zoledronic acid	Zoledronic acid	Group 2 - FES-Rowing Exercise for entire study period plus Zoledronic Acid 5mg administered by i.v. infusion one-time at the end of observation period

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.