Clinical trial NCT02325414: Prevention of Bone Loss After Acute SCI by Zoledronic Acid
Official title: Prevention of Bone Loss After Acute SCI by Zoledronic Acid: Durability, Effect on Bone Strength, and Use of Biomarkers to Guide Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Spinal Cord Injury
Acute Spinal Cord Injury
Bone Loss
Osteoporosis
Keywords: Osteoporosis
Spinal Cord Injury
Bone Diseases
Metabolic Bone Diseases
Musculoskeletal Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Nervous System
Wounds and Injuries
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Department of Defense
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2014-12-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent Change in Bone Mass Density (BMD) in the Hip
timeFrame: 0-12 months
measure: Percent Change of Bone Mass Density (BMD) in the Femoral Neck
timeFrame: 0-12 months
Secondary outcomes:
measure: Percent Change in the Epiphyseal Integral Bone Mass Content (iBMC) of the Femur
timeFrame: 0-12 months
measure: Percent Change in the Metaphyseal Integral Bone Mass Content (iBMC) of the Femur
timeFrame: 0-12 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: Rehabilitation Institute of Chicago
state: Illinois
Study officials:
affiliation: Northwestern University Feinberg School of Medicine
name: Thomas J Schnitzer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Edwards WB, Haider IT, Simonian N, Barroso J, Schnitzer TJ. Durability and delayed treatment effects of zoledronic acid on bone loss after spinal cord injury: a randomized, controlled trial. J Bone Miner Res. 2021 Nov;36(11):2127-2138. doi: 10.1002/jbmr.4416. Epub 2021 Jul 29.
citation: Haider IT, Lobos SM, Simonian N, Schnitzer TJ, Edwards WB. Bone fragility after spinal cord injury: reductions in stiffness and bone mineral at the distal femur and proximal tibia as a function of time. Osteoporos Int. 2018 Dec;29(12):2703-2715. doi: 10.1007/s00198-018-4733-0. Epub 2018 Oct 17.