Prevention of Bone Loss After Acute SCI by Zoledronic Acid

Phase 2

Completed

Conditions: Bone Loss
Spinal Cord Injury
Osteoporosis
Acute Spinal Cord Injury

Brief Summary: The overall objective of this study is to define an effective therapeutic approach, using currently available medication, to prevent or mitigate the loss of bone mass and bone strength that occurs after acute spinal cord injury.

Detailed Description: This is a randomized, double-blind placebo-controlled study of zoledronic acid to evaluate its efficacy and safety over a 2 year period for the prevention of bone loss and maintenance of bone strength in individuals with recent onset SCI (see diagram below). Subjects will be randomized at the baseline visit to receive either zoledronic acid or placebo. At the end of the first year of the study, each treatment group will be re-randomized to either zoledronic acid or placebo to evaluate the durability of response to zoledronic acid and the utility of serum bone markers to guide therapeutic decision making. DXA imaging, CT imaging and bone markers will be obtained at baseline, 3 months, 6 months, 12 months, 18 months and 24 months.

Recruitment & Eligibility

Inclusion Criteria

In-patient at Rehabilitation Institute of Chicago (RIC) or an outpatient who was recently discharged from RIC
Males and females
Age >/=18 years
Medically stable in the opinion of subject's physiatrist
SCI at within 120 days inclusive at time of screening
SCI with inability to ambulate independently
ASIA Impairment Scale (AIS) A, B, or C, at time of study entry
Capable of positioning to have DXA performed
Able to tolerate acetaminophen
No known endocrinopathies (diabetes type 1 or 2 can be included)
Normal TSH levels
Normal 25-OH vitamin D levels (>/= 20 ng/ml) at baseline (subjects may be repleted)
Normal calcium levels
Normal renal function (creatinine <2.0 mg/dl)
Well hydrated with adequate intake of liquids
Able to return for all follow-up visits
Capable of reading and understanding informed consent document
Males and females of childbearing potential must be willing and able to use double barrier method of contraception for 2 months after having received study drug

Exclusion Criteria

Have Paget's disease of the bone
Malignancy as a cause of acute SCI
Have unexplained high levels of alkaline phosphatase in blood
Any active gastrointestinal condition that results in malabsorption
Poor dental hygiene or requirement for invasive dental procedure within two months prior to enrollment
History of bone metastasis and skeletal malignancies
History of alcoholism or drug abuse within the 2 years prior to study screening
Other medical conditions that in the opinion of the investigator would preclude the subject from completing the study
Elevated liver function tests >2x normal
Currently being prescribed anti-convulsants at a dose or frequency that is determined to interfere with bone metabolism as determined by the investigator
Currently being prescribed glucocorticoids, other than inhaled glucocorticoids
Current or recent use any bone-active agents, including any bisphosphonate, raloxifene, hormone therapy (estrogen and estrogen/progestin), calcitonin or strontium-containing compounds within 60 days of screening.
Pregnant, planning to become pregnant, or lactating

Arm && Interventions

Group	Intervention	Description
Zol	Zoledronic acid	Intravenous infusion of zoledronic acid (zol) 5 mg at baseline.
Placebo	Placebo	Intravenous infusion of placebo at baseline.

Primary Outcome Measures

Name	Time	Method
Percent Change of Bone Mass Density (BMD) in the Femoral Neck	0-12 months	Percent change of bone mass density (BMD) in the femoral neck (as measured by DXA)
Percent Change in Bone Mass Density (BMD) in the Hip	0-12 months	Percent change of bone mass density (BMD) in the total hip (as measured by DXA)

Secondary Outcome Measures

Name	Time	Method
Percent Change in the Epiphyseal Integral Bone Mass Content (iBMC) of the Femur	0-12 months	Percent change in the epiphyseal integral bone mass content (iBMC) of the femur, as collected by CT.
Percent Change in the Metaphyseal Integral Bone Mass Content (iBMC) of the Femur	0-12 months	Percent change in the metaphyseal integral bone mass content (iBMC) of the femur, as collected by CT

Locations (2): Rehabilitation Institute of Chicago
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Chicago, Illinois, United States
Northwestern University Feinberg School of Medicine
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Chicago, Illinois, United States