Zoledronic Acid Administration in Acute Spinal Cord Injury
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
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.
Other Names:
|
| No Intervention: No Intervention Participants will receive no therapy and serve as a control group and have the same outcome measures completed at parallel time points. |
Outcome Measures
Primary Outcome Measures
- Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12. [Baseline and 12 months]
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.
Secondary Outcome Measures
- Bone Mineral Density (BMD) at the Total Hip at Baseline and Month 12 [Baseline and 12 months]
An imaging method known as dual energy x-ray absorptiometry (DXA) was used to obtain BMD of the total hip.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Within 3 months of the date of acute SCI.
-
Motor-complete and incomplete SCI [American Spinal Injury Association Impairment Scale (AIS) of sensorimotor impairment (AIS A, B, and C)]
Exclusion Criteria:
-
Extensive life-threatening injuries (in addition to SCI)
-
Femur or tibia fracture or extensive bone trauma
-
History of prior bone disease (Paget's disease, overactive parathyroid, osteoporosis)
-
Post-menopausal women
-
Known allergy to bisphosphonates
-
Severe underlying chronic illness
-
Current diagnosis of cancer or history of cancer
-
I am currently receiving corticosteroids
-
Pregnancy or lactation
-
I have been diagnosed with kidney problems
-
As determined from the prescreening blood tests by the study physician Serum creatinine > 2.0 mg/dl
-
As determined from the prescreening blood tests by the study physician Corrected calcium < 8 mg/dl or > 11 mg/dl
-
As determined from the prescreening blood tests by the study physician Elevated liver function enzymes > 2 x upper limit of normal (ULN)
-
I am taking a bisphosphonate for heterotopic ossification (HO) (an overgrowth of bone typically diagnosed shortly after SCI in the pelvic region)
-
I have an existing dental condition or dental infection.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Kessler Institute for Rehabilitation | West Orange | New Jersey | United States | 07052 |
Sponsors and Collaborators
- James J. Peters Veterans Affairs Medical Center
- Kessler Institute for Rehabilitation
Investigators
- Principal Investigator: William A Bauman, M.D., James J. Peters VA Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 5481-03-0013
- R-454-03
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Zoledronic Acid | No Treatment |
|---|---|---|
| Arm/Group Description | 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. | Participants will receive no therapy and serve as a control group and have the same outcome measures completed at parallel time points. |
| Period Title: Overall Study | ||
| STARTED | 8 | 13 |
| COMPLETED | 8 | 8 |
| NOT COMPLETED | 0 | 5 |
Baseline Characteristics
| Arm/Group Title | Zoledronic Acid | No Treatment | Total |
|---|---|---|---|
| Arm/Group Description | 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. | Participants will receive no therapy and serve as a control group and have the same outcome measures completed at parallel time points. | Total of all reporting groups |
| Overall Participants | 8 | 13 | 21 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
25.5
(9.6)
|
33.0
(11.0)
|
29.3
(20.7)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
1
12.5%
|
1
7.7%
|
2
9.5%
|
| Male |
7
87.5%
|
12
92.3%
|
19
90.5%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
8
100%
|
13
100%
|
21
100%
|
Outcome Measures
| Title | Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12. |
|---|---|
| Description | 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. |
| Time Frame | Baseline and 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Zoledronic Acid | No Treatment |
|---|---|---|
| Arm/Group Description | 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. | Participants will receive no therapy and serve as a control group and have the same outcome measures completed at parallel time points. |
| Measure Participants | 8 | 13 |
| Baseline Distal Femur |
1.102
(0.148)
|
1.134
(0.244)
|
| 12 Month Distal Femur |
0.898
(0.128)
|
1.038
(0.241)
|
| Baseline Proximal Tibia |
1.274
(0.245)
|
1.341
(1.216)
|
| 12 Month Proximal Tibia |
1.022
(0.267)
|
1.237
(0.276)
|
| Title | Bone Mineral Density (BMD) at the Total Hip at Baseline and Month 12 |
|---|---|
| Description | An imaging method known as dual energy x-ray absorptiometry (DXA) was used to obtain BMD of the total hip. |
| Time Frame | Baseline and 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Zoledronic Acid | No Treatment |
|---|---|---|
| Arm/Group Description | 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. | Participants will receive no therapy and serve as a control group and have the same outcome measures completed at parallel time points. |
| Measure Participants | 8 | 13 |
| Baseline Total Hip |
1.125
(0.166)
|
1.020
(0.154)
|
| 12 Month Total Hip |
1.042
(0.168)
|
0.814
(0.151)
|
Adverse Events
| Time Frame | 24 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Monthly assessment of medical history over the 24 month follow-up period after baseline assessment. | |||
| Arm/Group Title | Zoledronic Acid | No Treatment | ||
| Arm/Group Description | 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. | Participants will receive no therapy and serve as a control group and have the same outcome measures completed at parallel time points. | ||
All Cause Mortality |
||||
| Zoledronic Acid | No Treatment | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Zoledronic Acid | No Treatment | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/8 (37.5%) | 1/13 (7.7%) | ||
| Blood and lymphatic system disorders | ||||
| Deep Venous Thrombosis | 1/8 (12.5%) | 1 | 1/13 (7.7%) | 1 |
| Gastrointestinal disorders | ||||
| Bowel Impaction | 1/8 (12.5%) | 1 | 0/13 (0%) | 0 |
| Nervous system disorders | ||||
| Spinal headache | 1/8 (12.5%) | 1 | 0/13 (0%) | 0 |
| Renal and urinary disorders | ||||
| Urinary Tract Infection | 0/8 (0%) | 0 | 1/13 (7.7%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Decubitus Ulcer | 1/8 (12.5%) | 1 | 0/13 (0%) | 0 |
| Surgical and medical procedures | ||||
| General Surgery | 3/8 (37.5%) | 3 | 1/13 (7.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Zoledronic Acid | No Treatment | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/8 (100%) | 0/13 (0%) | ||
| Blood and lymphatic system disorders | ||||
| Hypocalcemia | 1/8 (12.5%) | 8 | 0/13 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Vomiting | 6/8 (75%) | 8 | 0/13 (0%) | 0 |
| General disorders | ||||
| Acute Febrile Reaction | 6/8 (75%) | 8 | 0/13 (0%) | 0 |
| Lethargy | 8/8 (100%) | 8 | 0/13 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Myalgia | 8/8 (100%) | 8 | 0/13 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | William A. Bauman, M.D. |
|---|---|
| Organization | James J. Peters VA Medical Center |
| Phone | 718-584-9000 ext 5428 |
| william.bauman@va.gov |
- 5481-03-0013
- R-454-03