Zoledronic Acid Administration in Acute Spinal Cord Injury

NCT ID: NCT02042872

Last Updated: 2018-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2012-07-31

Brief 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).

Detailed 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.

Conditions

Disuse Osteoporosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Zoledronic acid

Intervention Type: DRUG

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.

No Intervention

Participants will receive no therapy and serve as a control group and have the same outcome measures completed at parallel time points.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Zometa; Reclast

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kessler Institute for Rehabilitation

INDUSTRY

Sponsor Role: collaborator

James J. Peters Veterans Affairs Medical Center

FED

Sponsor Role: lead

Responsible Party

William A. Bauman, M.D.

Director VA RR&D Center of Excellence for the Medical Consequences of SCI

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William A Bauman, M.D.

Role: PRINCIPAL_INVESTIGATOR

James J. Peters VA Medical Center

Locations

Kessler Institute for Rehabilitation

West Orange, New Jersey, United States

Countries

United States

References

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. doi: 10.1007/s00223-007-9012-6. Epub 2007 Apr 7.

Reference Type: BACKGROUND

PMID: 17417700 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20358358 (View on PubMed)

Other Identifiers

R-454-03

Identifier Type: OTHER

Identifier Source: secondary_id

5481-03-0013

Identifier Type: -

Identifier Source: org_study_id