Trial Outcomes & Findings for The Impact of Parathyroid Hormone (PTH) on Craniofacial Osseous Regeneration in Bone (NCT NCT01279187)
NCT ID: NCT01279187
Last Updated: 2018-02-07
Results Overview
To determine the impact of PTH on bone quality and bone turnover in the oral cavity. The primary outcome variable will be bone formation rate.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
27 participants
Primary outcome timeframe
10 weeks
Results posted on
2018-02-07
Participant Flow
Participant milestones
| Measure |
Teriparatide
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Teriparatide: 20ug per day,via subcutaneous injection, for 7 weeks
|
Control
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Placebo: 20ug per day, self administered injection, for 7 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
14
|
13
|
|
Overall Study
COMPLETED
|
14
|
13
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Impact of Parathyroid Hormone (PTH) on Craniofacial Osseous Regeneration in Bone
Baseline characteristics by cohort
| Measure |
Teriparatide
n=14 Participants
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Teriparatide: 20ug per day,via subcutaneous injection, for 7 weeks
|
Control
n=13 Participants
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Placebo: 20ug per day, self administered injection, for 7 weeks
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54 years
n=5 Participants
|
53.5 years
n=7 Participants
|
53.95 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
14 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 10 weeksTo determine the impact of PTH on bone quality and bone turnover in the oral cavity. The primary outcome variable will be bone formation rate.
Outcome measures
| Measure |
Teriparatide
n=14 Participants
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Teriparatide: 20ug per day,via subcutaneous injection, for 7 weeks
|
Control
n=13 Participants
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Placebo: 20ug per day, self administered injection, for 7 weeks
|
|---|---|---|
|
Bone Formation Rate
|
1.76 mm2/week
Standard Deviation 0.99
|
2.22 mm2/week
Standard Deviation 1.67
|
SECONDARY outcome
Timeframe: 10 weeksBone turnover was assessed indirectly by bone histomorphometry using the following abbreviations: Mineral Apposition Rate (MAR): Distance between 2 fluorochrome markers that comprise a double label on the surfaces of cancellous bone measured at an average of 4 equally-spaced sites per double label. These measurements will be performed on 20 double fluorochrome labels per bone and the average divided by the time between the midpoints of the two labeling periods. MAR serves as an index of osteoblast activity. Reported for cancellous (Cn), endocortical (Ec) at baseline (pre-drug intervention, listed as "first set") and at the end of drug intervention ("second set"). "First set" refers to baseline information (pre-drug), and "second set" refers to data evaluated at the end of the drug administration phase. Periosteal (Ps) data and Ec.Mar Endocortical MAR "second set" was reviewed but no analyzable labeling was noted and so this data is not reported.
Outcome measures
| Measure |
Teriparatide
n=14 Participants
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Teriparatide: 20ug per day,via subcutaneous injection, for 7 weeks
|
Control
n=13 Participants
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Placebo: 20ug per day, self administered injection, for 7 weeks
|
|---|---|---|
|
Bone Turnover (Mineral Apposition Rates)
Cn.MAR (Cancellous MAR) - first set
|
0.5 um/day
Standard Deviation 0.1
|
0.3 um/day
Standard Deviation 0.2
|
|
Bone Turnover (Mineral Apposition Rates)
Ec.MAR Endocortical MAR - first set
|
0.7 um/day
Standard Deviation 0.7
|
0.6 um/day
Standard Deviation 0.4
|
|
Bone Turnover (Mineral Apposition Rates)
Cn.MAR Cancellous MAR- second set
|
0.2 um/day
Standard Deviation 0.2
|
0.3 um/day
Standard Deviation 0.2
|
SECONDARY outcome
Timeframe: 10 weeksBone turnover was assessed indirectly by evaluating cellular parameters of PTH action (i.e. numbers of osteoblasts, osteoclasts, apoptotic osteoblasts). The methods used to obtain the outcomes described below were bone histomorphometry using the following abbreviation: Ct.T.Ar: Ct Cort(ex)(ical) Tissue Area (2D)b "First set" refers to baseline pre-drug data and "second set" was taken at the end of the drug administration phase.
Outcome measures
| Measure |
Teriparatide
n=14 Participants
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Teriparatide: 20ug per day,via subcutaneous injection, for 7 weeks
|
Control
n=13 Participants
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Placebo: 20ug per day, self administered injection, for 7 weeks
|
|---|---|---|
|
Bone Turnover: Cortical Tissue Area
Ct.T.Ar first set Cortical Tissue Area
|
2.2 mm2/week
Standard Deviation 1.6
|
1.8 mm2/week
Standard Deviation 1
|
|
Bone Turnover: Cortical Tissue Area
Ct. T.Ar second set Cortical Tissue Area
|
2.2 mm2/week
Standard Deviation 1.6
|
1.8 mm2/week
Standard Deviation 0.9
|
SECONDARY outcome
Timeframe: 10 weeksBone histomorphometry was used to assess bone perimeter length in mm as follows: Cn.Pm cancellous: Cancellous Bone Perimeter Ec.Pm: endocortical bone perimeter Ps.Pm: Periosteal Periosteal bone perimeter
Outcome measures
| Measure |
Teriparatide
n=14 Participants
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Teriparatide: 20ug per day,via subcutaneous injection, for 7 weeks
|
Control
n=13 Participants
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Placebo: 20ug per day, self administered injection, for 7 weeks
|
|---|---|---|
|
Bone Turnover: Bone Perimeter Length
Cn.Pm cancellous Cancellous bone Perimeter
|
20.8 mm
Standard Deviation 11.1
|
18.7 mm
Standard Deviation 9.6
|
|
Bone Turnover: Bone Perimeter Length
Ec.Pm endocortical bone perimeter
|
2.9 mm
Standard Deviation 1.5
|
3.6 mm
Standard Deviation 1.3
|
|
Bone Turnover: Bone Perimeter Length
Ps.Pm Periosteal Periosteal bone perimeter
|
4.1 mm
Standard Deviation 0.9
|
4.3 mm
Standard Deviation 1.1
|
SECONDARY outcome
Timeframe: 10 weeksOc.S/BS cancellous: Osteoclast suface divided by bone surface. Osteoclastic surface as percent of total bone surface in cancellous bone. Percent cancellous bone perimeter with osteoclasts (large, multinuclear, TRAP positive cells). OS/BS cancellous: Osteoid surface divided by bone surface. Percentage of cancellous bone perimeter covered with osteoid. Oc.S/BS endocortical: Osteoclastic surface as percent of total bone surface in endocortical bone. OS/BS endocortical: Percentage of endocortical bone perimeter covered with osteoid. Oc.S/BS Periosteal: Osteoclastic surface as percent of total bone surface in periosteal bone. Ob.S/BS Periosteal: Percent periosteal bone perimeter with osteoid and adjacent osteoblasts, identified as plump cells with a single, eccentric nucleus and a pale-staining golgi apparatus. Osteoblast Surface divided by bone surface in periosteal bone. OS/BS Periosteal: Percentage of periosteal bone perimeter covered with osteoid.
Outcome measures
| Measure |
Teriparatide
n=14 Participants
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Teriparatide: 20ug per day,via subcutaneous injection, for 7 weeks
|
Control
n=13 Participants
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Placebo: 20ug per day, self administered injection, for 7 weeks
|
|---|---|---|
|
Bone Turnover: Bone Percentages
Oc.S/BS cancellous
|
0.34 percentage (%)
Standard Deviation 0.42
|
0.15 percentage (%)
Standard Deviation 0.21
|
|
Bone Turnover: Bone Percentages
OS/BS cancellous
|
8 percentage (%)
Standard Deviation 10
|
12 percentage (%)
Standard Deviation 11
|
|
Bone Turnover: Bone Percentages
Oc.S/BS endocortical
|
0 percentage (%)
Standard Deviation 0
|
0.3 percentage (%)
Standard Deviation 0.7
|
|
Bone Turnover: Bone Percentages
OS/BS endocortical
|
14 percentage (%)
Standard Deviation 27
|
17 percentage (%)
Standard Deviation 23
|
|
Bone Turnover: Bone Percentages
Oc.S/BS Periosteal
|
0.1 percentage (%)
Standard Deviation 0.2
|
0.4 percentage (%)
Standard Deviation 1.2
|
|
Bone Turnover: Bone Percentages
Ob.S/BS Periosteal
|
6 percentage (%)
Standard Deviation 13
|
5 percentage (%)
Standard Deviation 11
|
|
Bone Turnover: Bone Percentages
OS/BS Periosteal
|
5 percentage (%)
Standard Deviation 22
|
25 percentage (%)
Standard Deviation 28
|
Adverse Events
Teriparatide
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Control
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Teriparatide
n=14 participants at risk
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Teriparatide: 20ug per day,via subcutaneous injection, for 7 weeks
|
Control
n=13 participants at risk
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Placebo: 20ug per day, self administered injection, for 7 weeks
|
|---|---|---|
|
General disorders
Debonded Crown
|
21.4%
3/14 • Number of events 4 • 59 weeks
|
61.5%
8/13 • Number of events 13 • 59 weeks
|
|
General disorders
Implant Failure
|
28.6%
4/14 • Number of events 4 • 59 weeks
|
46.2%
6/13 • Number of events 6 • 59 weeks
|
|
General disorders
Thrush
|
7.1%
1/14 • Number of events 1 • 59 weeks
|
0.00%
0/13 • 59 weeks
|
|
General disorders
Shingles
|
0.00%
0/14 • 59 weeks
|
7.7%
1/13 • Number of events 1 • 59 weeks
|
|
General disorders
Sore Throat
|
7.1%
1/14 • Number of events 2 • 59 weeks
|
0.00%
0/13 • 59 weeks
|
|
General disorders
Metallic taste
|
0.00%
0/14 • 59 weeks
|
7.7%
1/13 • Number of events 1 • 59 weeks
|
|
General disorders
Leg Cramps
|
7.1%
1/14 • Number of events 1 • 59 weeks
|
0.00%
0/13 • 59 weeks
|
|
General disorders
Constipation
|
0.00%
0/14 • 59 weeks
|
7.7%
1/13 • Number of events 1 • 59 weeks
|
|
General disorders
Joint pain
|
0.00%
0/14 • 59 weeks
|
15.4%
2/13 • Number of events 2 • 59 weeks
|
|
General disorders
Indigestion
|
7.1%
1/14 • Number of events 2 • 59 weeks
|
0.00%
0/13 • 59 weeks
|
|
General disorders
Discontinuation of Drug
|
0.00%
0/14 • 59 weeks
|
7.7%
1/13 • Number of events 1 • 59 weeks
|
|
General disorders
Flu
|
7.1%
1/14 • Number of events 1 • 59 weeks
|
7.7%
1/13 • Number of events 1 • 59 weeks
|
|
General disorders
headache
|
7.1%
1/14 • Number of events 1 • 59 weeks
|
0.00%
0/13 • 59 weeks
|
|
General disorders
rotator cuff injury
|
7.1%
1/14 • Number of events 1 • 59 weeks
|
0.00%
0/13 • 59 weeks
|
|
General disorders
Pt received tetanus shot
|
0.00%
0/14 • 59 weeks
|
7.7%
1/13 • Number of events 1 • 59 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place