Bone Loss, Osteoporosis, Spinal Cord Injury
Conditions
Brief summary
Spinal cord injury (SCI) results in marked acute loss of bone. This study evaluates the effect of teriparatide (PTH) and the use of vibration as a form of mechanical stimulation on bone mass.
Detailed description
The aim of this study is to evaluate PTH with vibration in a group of individuals with chronic SCI and loss of bone mass in their lower extremities. A convenience sample of 60 subjects with SCI will be enrolled into a 12 month study assessing the effects of PTH (20 ug/day) and vibration (10 min/day) individually or in combination on BMD and bone markers. Subjects will be evaluated at 3, 6, 9, and 12 months after initiating treatment with measurement of bone density as well as bone markers of formation and resorption.
Interventions
DRUGTeriparatide
20 ug daily over 12 months
DEVICEvibration
10 min/day for 12 months
Sponsors
Edward Hines Jr. VA Hospital
University of Illinois at Chicago
Congressionally Directed Medical Research Program
Thomas J. Schnitzer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Age \>21 years (must have closed epiphyses; PTH contraindicated if epiphyses open) * Both males and females * SCI with inability to ambulate independently * Capable of positioning to have DXA performed * Low bone mass at the total hip by DEXA (Z score \< 1.5; T score \< 2.5 or T score \<-2.0 plus preexisting fragility fracture) * Capable of reading and understanding informed consent document * Able to self-administer teriparatide or have someone in the family who can do so * No known endocrinopathies * Normal TSH levels * Normal 25-OH vitamin D levels (\> 30ng/ml) * Normal calcium levels * Normal renal function (creatinine \<2.0mg/dl) * Able to return for all follow-up visits
Exclusion criteria
Surgical or other intervention resulting in metal or anatomy precluding obtaining DXA measurements (e.g., cardiac pacemakers, ferromagnetic implants or brain aneurysm clips). * Had had an allergic reaction to Teriparatide (FORTEO) or one of its ingredients. * Have Paget's disease of the bone * Have unexplained high levels of f alkaline phosphatase in blood * Any active Gastrointestinal condition that results in malabsorption * History of presence 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 * History of malignancy. Patients having had basal cell carcinomas successfully removed will be allowed to enroll in the protocol. * History of radiation therapy * Unable to self-administer PTH or have it administered * Elevated liver function tests \>2x normal * Currently being prescribed anti-convulsants * Currently being prescribed glucocorticoids, other than inhaled glucocorticoids * Currently being prescribed any bone-active agents, including any bisphosphonate, raloxifene, hormone therapy (estrogen and estrogen/progestin), calcitonin or strontium-containing compounds. Bisphosphonate use will be allowed up the time of initiation of study medication but not during the dosing with study medication. * Previous history of PTH use * Pregnant, planning to become pregnant, or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone Mineral Density BMD of the Total Hip as Assessed by DXA. | Baseline to 12 Months | The mean change in BMD of the total hip after 12 month of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bone Mineral Density (BMD) by DXA at the Lumbar Spine. | Baseline to 12 Months | The mean change in BMD at the lumbar spine from baseline after 12 month of treatment |
| Bone Mineral Density (BMD) by DXA at Femoral Neck | Baseline to 12 Months | The mean change in BMD of the femoral neck after 12 month of treatment |
| C-terminal Telopeptide | Baseline to 12 Months | The mean change in C-terminal telopeptide from baseline after 12 month of treatment |
| Bone-specific Alkaline Phosphatase | Baseline to 12 Months | The mean change in Bone-specific alkaline phosphatase from baseline after 12 month of therapy |
| Amino-terminal Propeptide of Type 1 Collagen | Baseline to 12 Months | The mean change in Amino-terminal of type 1 collagen from baseline after 12 months of treatment |
Countries
United States
Participant flow
Pre-assignment details
One subject withdrew prior to receiving therapy from the Teriparatide and Vibration group. After consenting the subject did not participate in the study.. This accounts for the 61 in Participant Flow but 60 that were enrolled and started treatment according to their assigned group.
Participants by arm
| Arm | Count |
|---|---|
| Teriparatide Teriparatide alone with sham vibration
Teriparatide: 20 ug daily over 12 months | 20 |
| Vibration Vibration alone with placebo-teriparatide
vibration: 10 min/day for 12 months | 20 |
| Teriparatide and Vibration Teriparatide with vibration applied in conjuction
Teriparatide: 20 ug daily over 12 months
vibration: 10 min/day for 12 months | 21 |
| Total | 61 |
Baseline characteristics
| Characteristic | Teriparatide | Teriparatide and Vibration | Total | Vibration |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 8 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 19 Participants | 53 Participants | 18 Participants |
| Age, Continuous | 47.6 years STANDARD_DEVIATION 16.3 | 46.6 years STANDARD_DEVIATION 15.4 | 45.4 years STANDARD_DEVIATION 16.3 | 40.9 years STANDARD_DEVIATION 16.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 6 Participants | 16 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 15 Participants | 45 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 14 Participants | 33 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 7 Participants | 25 Participants | 7 Participants |
| Region of Enrollment United States | 20 participants | 21 participants | 60 participants | 20 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 14 Participants | 6 Participants |
| Sex: Female, Male Male | 17 Participants | 16 Participants | 47 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 16 / 20 | 16 / 20 | 16 / 20 |
| serious Total, serious adverse events | 7 / 20 | 1 / 20 | 8 / 20 |
Outcome results
Primary
Bone Mineral Density BMD of the Total Hip as Assessed by DXA.
The mean change in BMD of the total hip after 12 month of treatment
Time frame: Baseline to 12 Months
Population: One subject withdrew prior to receiving therapy. The samples from the Hines location (n=11) were also not included. Two additional subjects were not analyzed due to metal artifacts or heterotopic ossification that interfered with analysis. This accounts for the 14 subjects that were not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Bone Mineral Density BMD of the Total Hip as Assessed by DXA. | 0 months | 0.66 g/cm^2 | Standard Deviation 0.03 |
| Teriparatide | Bone Mineral Density BMD of the Total Hip as Assessed by DXA. | 3 months | 0.65 g/cm^2 | Standard Deviation 0.03 |
| Teriparatide | Bone Mineral Density BMD of the Total Hip as Assessed by DXA. | 6 months | 0.67 g/cm^2 | Standard Deviation 0.03 |
| Teriparatide | Bone Mineral Density BMD of the Total Hip as Assessed by DXA. | 12 months | 0.66 g/cm^2 | Standard Deviation 0.03 |
| Vibration | Bone Mineral Density BMD of the Total Hip as Assessed by DXA. | 12 months | 0.64 g/cm^2 | Standard Deviation 0.03 |
| Vibration | Bone Mineral Density BMD of the Total Hip as Assessed by DXA. | 0 months | 0.63 g/cm^2 | Standard Deviation 0.03 |
| Vibration | Bone Mineral Density BMD of the Total Hip as Assessed by DXA. | 6 months | 0.63 g/cm^2 | Standard Deviation 0.03 |
| Vibration | Bone Mineral Density BMD of the Total Hip as Assessed by DXA. | 3 months | 0.63 g/cm^2 | Standard Deviation 0.03 |
| Teriparatide and Vibration | Bone Mineral Density BMD of the Total Hip as Assessed by DXA. | 12 months | 0.65 g/cm^2 | Standard Deviation 0.03 |
| Teriparatide and Vibration | Bone Mineral Density BMD of the Total Hip as Assessed by DXA. | 3 months | 0.65 g/cm^2 | Standard Deviation 0.03 |
| Teriparatide and Vibration | Bone Mineral Density BMD of the Total Hip as Assessed by DXA. | 6 months | 0.65 g/cm^2 | Standard Deviation 0.03 |
| Teriparatide and Vibration | Bone Mineral Density BMD of the Total Hip as Assessed by DXA. | 0 months | 0.64 g/cm^2 | Standard Deviation 0.03 |
p-value: 0.84ANOVA
p-value: 0.64ANOVA
p-value: 0.26ANOVA
Secondary
Amino-terminal Propeptide of Type 1 Collagen
The mean change in Amino-terminal of type 1 collagen from baseline after 12 months of treatment
Time frame: Baseline to 12 Months
Population: One subject withdrew prior to receiving therapy from the Teriparatide and Vibration group. One sample was lost due to laboratory error. The samples from the Hines location (n=11) were also not included in this analysis. This accounts for the 13 subjects that were not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Amino-terminal Propeptide of Type 1 Collagen | 0 months | 67.1 ng/ml | Standard Deviation 8.9 |
| Teriparatide | Amino-terminal Propeptide of Type 1 Collagen | 3 months | 128 ng/ml | Standard Deviation 12.9 |
| Teriparatide | Amino-terminal Propeptide of Type 1 Collagen | 6 months | 163 ng/ml | Standard Deviation 30.4 |
| Teriparatide | Amino-terminal Propeptide of Type 1 Collagen | 12 months | 124 ng/ml | Standard Deviation 13.5 |
| Vibration | Amino-terminal Propeptide of Type 1 Collagen | 12 months | 49.8 ng/ml | Standard Deviation 12.7 |
| Vibration | Amino-terminal Propeptide of Type 1 Collagen | 0 months | 64.7 ng/ml | Standard Deviation 8.36 |
| Vibration | Amino-terminal Propeptide of Type 1 Collagen | 6 months | 54.5 ng/ml | Standard Deviation 28.6 |
| Vibration | Amino-terminal Propeptide of Type 1 Collagen | 3 months | 51.8 ng/ml | Standard Deviation 12.1 |
| Teriparatide and Vibration | Amino-terminal Propeptide of Type 1 Collagen | 12 months | 77.0 ng/ml | Standard Deviation 13 |
| Teriparatide and Vibration | Amino-terminal Propeptide of Type 1 Collagen | 3 months | 90.1 ng/ml | Standard Deviation 12.5 |
| Teriparatide and Vibration | Amino-terminal Propeptide of Type 1 Collagen | 6 months | 125 ng/ml | Standard Deviation 29.4 |
| Teriparatide and Vibration | Amino-terminal Propeptide of Type 1 Collagen | 0 months | 67.9 ng/ml | Standard Deviation 8.61 |
p-value: 0ANOVA
p-value: 0.01ANOVA
p-value: 0.04ANOVA
Secondary
Bone Mineral Density (BMD) by DXA at Femoral Neck
The mean change in BMD of the femoral neck after 12 month of treatment
Time frame: Baseline to 12 Months
Population: One subject withdrew prior to receiving therapy. The samples from the Hines location (n=11) were also not included. One additional subjects was not analyzed due to metal artifacts or heterotopic ossification that interfered with analysis. This accounts for the 13 subjects that were not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Bone Mineral Density (BMD) by DXA at Femoral Neck | 0 months | 0.66 g/cm^2 | Standard Deviation 0.03 |
| Teriparatide | Bone Mineral Density (BMD) by DXA at Femoral Neck | 3 months | 0.66 g/cm^2 | Standard Deviation 0.04 |
| Teriparatide | Bone Mineral Density (BMD) by DXA at Femoral Neck | 6 months | 0.67 g/cm^2 | Standard Deviation 0.04 |
| Teriparatide | Bone Mineral Density (BMD) by DXA at Femoral Neck | 12 months | 0.66 g/cm^2 | Standard Deviation 0.03 |
| Vibration | Bone Mineral Density (BMD) by DXA at Femoral Neck | 12 months | 0.63 g/cm^2 | Standard Deviation 0.03 |
| Vibration | Bone Mineral Density (BMD) by DXA at Femoral Neck | 0 months | 0.63 g/cm^2 | Standard Deviation 0.03 |
| Vibration | Bone Mineral Density (BMD) by DXA at Femoral Neck | 6 months | 0.62 g/cm^2 | Standard Deviation 0.03 |
| Vibration | Bone Mineral Density (BMD) by DXA at Femoral Neck | 3 months | 0.64 g/cm^2 | Standard Deviation 0.04 |
| Teriparatide and Vibration | Bone Mineral Density (BMD) by DXA at Femoral Neck | 12 months | 0.63 g/cm^2 | Standard Deviation 0.03 |
| Teriparatide and Vibration | Bone Mineral Density (BMD) by DXA at Femoral Neck | 3 months | 0.63 g/cm^2 | Standard Deviation 0.04 |
| Teriparatide and Vibration | Bone Mineral Density (BMD) by DXA at Femoral Neck | 6 months | 0.63 g/cm^2 | Standard Deviation 0.04 |
| Teriparatide and Vibration | Bone Mineral Density (BMD) by DXA at Femoral Neck | 0 months | 0.62 g/cm^2 | Standard Deviation 0.03 |
p-value: 0.72ANOVA
p-value: 0.58ANOVA
p-value: 0.44ANOVA
Secondary
Bone Mineral Density (BMD) by DXA at the Lumbar Spine.
The mean change in BMD at the lumbar spine from baseline after 12 month of treatment
Time frame: Baseline to 12 Months
Population: One subject withdrew prior to receiving therapy. The samples from the Hines location (n=11) were also not included. Five additional subjects were not analyzed due to metal artifacts that interfered with analysis. This accounts for the 17 subjects that were not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Bone Mineral Density (BMD) by DXA at the Lumbar Spine. | 0 months | 1.04 g/cm^2 | Standard Deviation 0.04 |
| Teriparatide | Bone Mineral Density (BMD) by DXA at the Lumbar Spine. | 3 months | 1.05 g/cm^2 | Standard Deviation 0.04 |
| Teriparatide | Bone Mineral Density (BMD) by DXA at the Lumbar Spine. | 6 months | 1.07 g/cm^2 | Standard Deviation 0.04 |
| Teriparatide | Bone Mineral Density (BMD) by DXA at the Lumbar Spine. | 12 months | 1.09 g/cm^2 | Standard Deviation 0.04 |
| Vibration | Bone Mineral Density (BMD) by DXA at the Lumbar Spine. | 12 months | 1.02 g/cm^2 | Standard Deviation 0.04 |
| Vibration | Bone Mineral Density (BMD) by DXA at the Lumbar Spine. | 0 months | 1.00 g/cm^2 | Standard Deviation 0.04 |
| Vibration | Bone Mineral Density (BMD) by DXA at the Lumbar Spine. | 6 months | 1.02 g/cm^2 | Standard Deviation 0.04 |
| Vibration | Bone Mineral Density (BMD) by DXA at the Lumbar Spine. | 3 months | 1.01 g/cm^2 | Standard Deviation 0.04 |
| Teriparatide and Vibration | Bone Mineral Density (BMD) by DXA at the Lumbar Spine. | 12 months | 1.07 g/cm^2 | Standard Deviation 0.04 |
| Teriparatide and Vibration | Bone Mineral Density (BMD) by DXA at the Lumbar Spine. | 3 months | 1.04 g/cm^2 | Standard Deviation 0.04 |
| Teriparatide and Vibration | Bone Mineral Density (BMD) by DXA at the Lumbar Spine. | 6 months | 1.05 g/cm^2 | Standard Deviation 0.04 |
| Teriparatide and Vibration | Bone Mineral Density (BMD) by DXA at the Lumbar Spine. | 0 months | 1.02 g/cm^2 | Standard Deviation 0.04 |
p-value: 0.64ANOVA
p-value: 0ANOVA
p-value: 0.09ANOVA
Secondary
Bone-specific Alkaline Phosphatase
The mean change in Bone-specific alkaline phosphatase from baseline after 12 month of therapy
Time frame: Baseline to 12 Months
Population: One subject withdrew prior to receiving therapy from the Teriparatide and Vibration group. One sample was lost due to laboratory error. The samples from the Hines location (n=11) were also not included in this analysis. This accounts for the 13 subjects that were not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Bone-specific Alkaline Phosphatase | 0 months | 15.3 ng/ml | Standard Deviation 1.63 |
| Teriparatide | Bone-specific Alkaline Phosphatase | 3 months | 18.4 ng/ml | Standard Deviation 1.81 |
| Teriparatide | Bone-specific Alkaline Phosphatase | 6 months | 20.3 ng/ml | Standard Deviation 2.64 |
| Teriparatide | Bone-specific Alkaline Phosphatase | 12 months | 20.4 ng/ml | Standard Deviation 1.58 |
| Vibration | Bone-specific Alkaline Phosphatase | 12 months | 11.8 ng/ml | Standard Deviation 1.48 |
| Vibration | Bone-specific Alkaline Phosphatase | 0 months | 13.9 ng/ml | Standard Deviation 1.53 |
| Vibration | Bone-specific Alkaline Phosphatase | 6 months | 11.3 ng/ml | Standard Deviation 2.48 |
| Vibration | Bone-specific Alkaline Phosphatase | 3 months | 11.6 ng/ml | Standard Deviation 1.7 |
| Teriparatide and Vibration | Bone-specific Alkaline Phosphatase | 12 months | 14.0 ng/ml | Standard Deviation 1.53 |
| Teriparatide and Vibration | Bone-specific Alkaline Phosphatase | 3 months | 12.8 ng/ml | Standard Deviation 1.75 |
| Teriparatide and Vibration | Bone-specific Alkaline Phosphatase | 6 months | 16.2 ng/ml | Standard Deviation 2.56 |
| Teriparatide and Vibration | Bone-specific Alkaline Phosphatase | 0 months | 12.4 ng/ml | Standard Deviation 1.58 |
p-value: 0.01ANOVA
p-value: 0.34ANOVA
p-value: 0.2ANOVA
Secondary
C-terminal Telopeptide
The mean change in C-terminal telopeptide from baseline after 12 month of treatment
Time frame: Baseline to 12 Months
Population: One subject withdrew prior to receiving therapy from the Teriparatide and Vibration group. One sample was lost due to laboratory error. The samples from the Hines location (n=11) were also not included in this analysis. This accounts for the 13 subjects that were not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | C-terminal Telopeptide | 0 months | 0.38 ng/ml | Standard Deviation 0.07 |
| Teriparatide | C-terminal Telopeptide | 3 months | 0.72 ng/ml | Standard Deviation 0.11 |
| Teriparatide | C-terminal Telopeptide | 6 months | 0.74 ng/ml | Standard Deviation 0.11 |
| Teriparatide | C-terminal Telopeptide | 12 months | 0.59 ng/ml | Standard Deviation 0.11 |
| Vibration | C-terminal Telopeptide | 12 months | 0.29 ng/ml | Standard Deviation 0.11 |
| Vibration | C-terminal Telopeptide | 0 months | 0.31 ng/ml | Standard Deviation 0.06 |
| Vibration | C-terminal Telopeptide | 6 months | 0.25 ng/ml | Standard Deviation 0.11 |
| Vibration | C-terminal Telopeptide | 3 months | 0.25 ng/ml | Standard Deviation 0.1 |
| Teriparatide and Vibration | C-terminal Telopeptide | 12 months | 0.45 ng/ml | Standard Deviation 0.11 |
| Teriparatide and Vibration | C-terminal Telopeptide | 3 months | 0.43 ng/ml | Standard Deviation 0.11 |
| Teriparatide and Vibration | C-terminal Telopeptide | 6 months | 0.44 ng/ml | Standard Deviation 0.11 |
| Teriparatide and Vibration | C-terminal Telopeptide | 0 months | 0.38 ng/ml | Standard Deviation 0.06 |
p-value: 0.02ANOVA
p-value: 0.1ANOVA
p-value: 0.04ANOVA