Zoledronic Acid Administration in Acute Spinal Cord Injury

Disuse Osteoporosis Clinical Trial

Official title:

The Efficacy of Zoledronic Acid in the Prevention of Bone Loss in Acute Spinal Cord Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02042872
• Other study ID #: 5481-03-0013
• Secondary ID: R-454-03
• Status: Completed
• Phase: Phase 4
• First received: January 21, 2014
• Last updated: March 12, 2018
• Start date: May 2006
• Est. completion date: July 2012

Study information

• Verified date: March 2018
• Source: James J. Peters Veterans Affairs Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In subjects with acute SCI: To compare the effects of parenteral zoledronic acid therapy on preservation of regional and total skeletal mass (DXA).

Hypothesis: Zoledronic acid will dramatically diminish bone loss in persons with acute SCI, as evidenced by serial densitometry determinations (DXA).

Description:

Immobilization is associated with disuse osteoporosis. Spinal cord injury (SCI) produces a syndrome of acute skeletal immobilization with immediate and irreversible unloading of the involved skeletal regions resulting in accelerated bone loss. In addition to rapid bone loss, there are also the complications of hypercalciuria, hypercalcemia, nephrolithiasis, and renal insufficiency. In some reports, as much as 50% of regional bone mass has been lost within the first year after paralysis. A depletion of regional bone of such magnitude greatly increases the risk of fractures, with associated morbidity and increased cost of care. Often, these fractures occur with minimal or non-obvious trauma and may pass undiagnosed for varying lengths of time due to the absence of pain sensation. The acute complications of fracture may include hemorrhage, deep venous thrombosis, and autonomic dysreflexia. Long-term complications include functional deformity, non-union, infection, heterotopic calcification, and significantly longer healing time. The sociology-economic consequences include a minimum of 1 to 2 weeks of hospitalization and the potential need for an increased level of attendant care. This study will address the efficacy of a bisphosphonate, zoledronic acid (Reclast: 5 mg; Novartis Pharmaceuticals Inc., East Hanover, NJ), in the prevention of the bone loss associated with acute SCI.

Prevention of regional osteoporosis in persons with SCI would reduce the morbidity associated with fractures, a known secondary complication of immobilization. Thus, the quality of life would be improved in terms of employment responsibilities (reduction in days absent from employment and income lost) and personal activities (recreational endeavors, independence, and ease in which one performs activities of daily living). Individuals with SCI may then engage more securely in activities without fear of fracture, a tremendous psychological benefit.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria:

1. Within 3 months of the date of acute SCI.

2. Motor-complete and incomplete SCI [American Spinal Injury Association Impairment Scale (AIS) of sensorimotor impairment (AIS A, B, and C)]

Exclusion Criteria:

1. Extensive life-threatening injuries (in addition to SCI)

2. Femur or tibia fracture or extensive bone trauma

3. History of prior bone disease (Paget's disease, overactive parathyroid, osteoporosis)

4. Post-menopausal women

5. Known allergy to bisphosphonates

6. Severe underlying chronic illness

7. Current diagnosis of cancer or history of cancer

8. I am currently receiving corticosteroids

9. Pregnancy or lactation

10. I have been diagnosed with kidney problems

11. As determined from the prescreening blood tests by the study physician Serum creatinine > 2.0 mg/dl

12. As determined from the prescreening blood tests by the study physician Corrected calcium < 8 mg/dl or > 11 mg/dl

13. As determined from the prescreening blood tests by the study physician Elevated liver function enzymes > 2 x upper limit of normal (ULN)

14. I am taking a bisphosphonate for heterotopic ossification (HO) (an overgrowth of bone typically diagnosed shortly after SCI in the pelvic region)

15. I have an existing dental condition or dental infection.

Related Conditions & MeSH terms

• Disuse Osteoporosis
• Osteoporosis
• Spinal Cord Injuries

Intervention

Drug:
• Zoledronic acid
At baseline, study subjects in the treatment group will receive 5 mg of zoledronic acid (Reclast: 5 mg; Novartis Pharmaceuticals Inc., East Hanover, NJ) by intravenous infusion over 30 minutes.

Locations

Country	Name	City	State
United States	Kessler Institute for Rehabilitation	West Orange	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
James J. Peters Veterans Affairs Medical Center	Kessler Institute for Rehabilitation

Country where clinical trial is conducted

United States, 

References & Publications (2)

Bubbear JS, Gall A, Middleton FR, Ferguson-Pell M, Swaminathan R, Keen RW. Early treatment with zoledronic acid prevents bone loss at the hip following acute spinal cord injury. Osteoporos Int. 2011 Jan;22(1):271-9. doi: 10.1007/s00198-010-1221-6. Epub 2010 Apr 1. — View Citation

Shapiro J, Smith B, Beck T, Ballard P, Dapthary M, BrintzenhofeSzoc K, Caminis J. Treatment with zoledronic acid ameliorates negative geometric changes in the proximal femur following acute spinal cord injury. Calcif Tissue Int. 2007 May;80(5):316-22. Epub 2007 Apr 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12.	An imaging method known as dual energy x-ray absorptiometry (DXA) was used to obtain BMD of the distal femur and proximal tibia by using a customized research software program supplied by the manufacturer. This measurement will be the primary determinant (dependent measure) of difference among the treatment and control groups, and they will be followed over time at the previously specified time points.	Baseline and 12 months
Secondary	Bone Mineral Density (BMD) at the Total Hip at Baseline and Month 12	An imaging method known as dual energy x-ray absorptiometry (DXA) was used to obtain BMD of the total hip.	Baseline and 12 months