ImplantPhase 2NCT01279187
The Impact of Parathyroid Hormone (PTH) on Craniofacial Osseous Regeneration in Bone
A Phase 2 study testing Teriparatide in people with Implant, run by University of Michigan at 1 site in United States.
Trial summary
Good bone healing and bone build-up are necessary for the success of dental implants. Research in animals and humans has shown that a drug, called Forteo, can increase bone build-up and bone strength over time. Read more about this study
- Who is it for?
- Ages 30 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Implant
- What is being tested?
- Teriparatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to Nov 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age range 30-85 yrs
- Sex: male and female (female subjects must be postmenopausal, surgically sterilized or utilizing birth control or abstinence throughout the period of Teriparatide administration)
- Subjects must be able and willing to follow study procedures and instructions;
- Subjects must have read, understood and signed an informed consent form;
- Subjects must have a need for the replacement of at least one tooth in the mandibular premolar/molar region with at least 12 months since the tooth extraction.
- Sites must be adaptable for dental implant placement without the necessity for grafting.
Who cannot join
- Subjects under 30 years or over 85 years of age,
- Female subjects who are pregnant, lactating, or female subjects who are of childbearing potential who are not using contraceptives,
- Subjects with metabolic bone diseases such as Paget's disease, hypercalcemia (mild to moderate hypocalcemia is acceptable for entry into the study), moderate to severe vitamin D3 abnormalities (If vitamin D levels are below 16 ng/ml and patient exhibits interest, dietary supplementation will be suggested and levels re-evaluated after 4 weeks and reconsidered for inclusion at that time), any other metabolic bone diseases including osteoporosis,
- Subjects with prior radiation therapy, bone metastases or other skeletal malignancy,
- Subjects on medications that would affect bone metabolism,
- Subjects with growth hormone deficiency,
Show all 12Show fewer
- Subjects with uncontrolled diabetes, sprue, inflammatory bowel disease or other disorders that would affect calcium absorption
- Subjects that are heavy smokers (> 1 pack/d),
- Subjects with tetracycline sensitivity or allergy,
- Subjects on bisphosphonates,
- Subjects with any form of kidney disease including kidney stones (urolithiasis and nephrolithiasis),
- Subjects with known allergies to tetracycline and/or demeclocycline,
Trial locations and contacts
1 site in 1 country.
United States1 site
Michigan Center for Oral Health Research
Ann Arbor, Michigan, 48106
About this study
Good bone healing and bone build-up are necessary for the success of dental implants. Research in animals and humans has shown that a drug, called Forteo, can increase bone build-up and bone strength over time. Forteo has been approved by the Food and Drug Administration (FDA) for use in patients with a condition where bone is broken down and weakened, called osteoporosis. The investigators do not know, however, whether Forteo is effective for use in humans for improving bone healing after implant placement, and whether it will have the same bone-building and bone-strengthening effects as for patients with osteoporosis. This research study is being done to learn what effect 7 weeks of treatment with Forteo will have on bone build-up and strengthening of bone for patients receiving implants.
Read the detailed description
A single center, placebo-controlled, double blind parallel study of teriparatide use in patients requiring dental implant therapy is planned. Subjects who qualify based on the inclusion/exclusion criteria will be randomly placed into one of two treatment groups, teriparatide (20 μg/day) or placebo control. Both patients and investigators will be blinded. Serum and gingival crevicular fluid (GCF) samples, radiographs, and a tetracycline-labelled bone core will constitute the main data gathered for analysis. After implant surgery, patients will return at 2 weeks for post-operative care and then at 14 weeks for an implant impression and again at 16 weeks to receive the final restoration. Twelve months after implant placement, patients will be seen for a follow-up exam and standardized radiograph to ensure proper healing.
- Conditions
- Implant
- Being tested
- Teriparatide, Placebo
- Keywords
- dental, implant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TeriparatideDrug
Also called Forteo
20ug per day,via subcutaneous injection, for 7 weeks
PlaceboDrug
Also called carrier
20ug per day, self administered injection, for 7 weeks
| Study group | Role | What they receive |
|---|---|---|
| Teriparatide | Experimental | 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. Receives: Drug: Teriparatide |
| Control | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bone Formation Rate
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.
Measured: 10 weeks
Secondary outcomes (4)
Bone Turnover (Mineral Apposition Rates)
Bone 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.
Measured: 10 weeks
Bone Turnover: Cortical Tissue Area
Bone 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.
Measured: 10 weeks
Bone Turnover: Bone Perimeter Length
Bone 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
Measured: 10 weeks
Bone Turnover: Bone Percentages
Oc.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.
Measured: 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2011 (estimated)
- Study startFeb 2011
- Primary completionMar 2015
- Study completionNov 2015
Why it stopped: Study was terminated due to patient complications unrelated to study drugs
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for ImplantStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Principal investigator, Jill Bashutski, University of Michigan
- Investigators
- Jill Bashutski, DDS, MS, Principal investigator, Faculty
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01279187
- Sponsor's protocol ID
- HUM00042770
- Status last verified
- Jan 2018
- First submitted
- 18 Jan 2011
- Last updated
- 7 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Hanley, D., et al., Pharmacologic mechanisms of therapeutics:Parathyroid Hormone, in Principles of Bone Biology, J. Bilezikian, L. Raisz, and T. Martin, Editors. 2008, Academic Press: San Diego. p. 1661-1695.
Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001 May 10;344(19):1434-41. doi: 10.1056/NEJM200105103441904.
PubMed 11346808Alkhiary YM, Gerstenfeld LC, Krall E, Westmore M, Sato M, Mitlak BH, Einhorn TA. Enhancement of experimental fracture-healing by systemic administration of recombinant human parathyroid hormone (PTH 1-34). J Bone Joint Surg Am. 2005 Apr;87(4):731-41. doi: 10.2106/JBJS.D.02115.
PubMed 15805200Chen H, Frankenburg EP, Goldstein SA, McCauley LK. Combination of local and systemic parathyroid hormone enhances bone regeneration. Clin Orthop Relat Res. 2003 Nov;(416):291-302. doi: 10.1097/01.blo.0000079443.64912.18.
PubMed 14646773
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Parathyroid Hormone (PTH) on Craniofacial Osseous Regeneration in Bone
- ClinicalTrials.gov ID
- NCT01279187
- Acronym / sponsor ID
- HUM00042770
- Conditions
- Implant
- Keywords
- dental, implant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to patient complications unrelated to study drugs
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- Feb 2011
- Primary completion
- Mar 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 19 Jan 2011 (estimated)
- Results
- Posted 7 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Good bone healing and bone build-up are necessary for the success of dental implants. Research in animals and humans has shown that a drug, called Forteo, can increase bone build-up and bone strength over time. Forteo has been approved by the Food and Drug Administration (FDA) for use in patients with a condition where bone is broken down and weakened, called osteoporosis. The investigators do not know, however, whether Forteo is effective for use in humans for improving bone healing after implant placement, and whether it will have the same bone-building and bone-strengthening effects as for patients with osteoporosis. This research study is being done to learn what effect 7 weeks of treatment with Forteo will have on bone build-up and strengthening of bone for patients receiving implants.
Detailed description
A single center, placebo-controlled, double blind parallel study of teriparatide use in patients requiring dental implant therapy is planned. Subjects who qualify based on the inclusion/exclusion criteria will be randomly placed into one of two treatment groups, teriparatide (20 μg/day) or placebo control. Both patients and investigators will be blinded. Serum and gingival crevicular fluid (GCF) samples, radiographs, and a tetracycline-labelled bone core will constitute the main data gathered for analysis. After implant surgery, patients will return at 2 weeks for post-operative care and then at 14 weeks for an implant impression and again at 16 weeks to receive the final restoration. Twelve months after implant placement, patients will be seen for a follow-up exam and standardized radiograph to ensure proper healing.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Teriparatide | Experimental | Drug: Teriparatidedemeclocycline 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. |
| Control | Placebo comparator | Drug: Placebodemeclocycline 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. |
Who may qualify
- Ages
- 30 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age range 30-85 yrs
- Sex: male and female (female subjects must be postmenopausal, surgically sterilized or utilizing birth control or abstinence throughout the period of Teriparatide administration)
- Subjects must be able and willing to follow study procedures and instructions;
- Subjects must have read, understood and signed an informed consent form;
- Subjects must have a need for the replacement of at least one tooth in the mandibular premolar/molar region with at least 12 months since the tooth extraction.
Key exclusion criteria (12 listed)
- Subjects under 30 years or over 85 years of age,
- Female subjects who are pregnant, lactating, or female subjects who are of childbearing potential who are not using contraceptives,
- Subjects with metabolic bone diseases such as Paget's disease, hypercalcemia (mild to moderate hypocalcemia is acceptable for entry into the study), moderate to severe vitamin D3 abnormalities (If vitamin D levels are below 16 ng/ml and patient exhibits interest, dietary supplementation will be suggested and levels re-evaluated after 4 weeks and reconsidered for inclusion at that time), any other metabolic bone diseases including osteoporosis,
- Subjects with prior radiation therapy, bone metastases or other skeletal malignancy,
- Subjects on medications that would affect bone metabolism,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TeriparatideAlso: Forteo20ug per day,via subcutaneous injection, for 7 weeks | Drug | Teriparatide |
| PlaceboAlso: carrier20ug per day, self administered injection, for 7 weeks | Drug | Control |
Primary outcome
Bone Formation Rate
Time frame: 10 weeks
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.
4 secondary outcomes
Bone Turnover (Mineral Apposition Rates)
Time frame: 10 weeks
Bone Turnover: Cortical Tissue Area
Time frame: 10 weeks
Bone Turnover: Bone Perimeter Length
Time frame: 10 weeks
Bone Turnover: Bone Percentages
Time frame: 10 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundHanley, D., et al., Pharmacologic mechanisms of therapeutics:Parathyroid Hormone, in Principles of Bone Biology, J. Bilezikian, L. Raisz, and T. Martin, Editors. 2008, Academic Press: San Diego. p. 1661-1695.
- Background: PubMed 11346808Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001 May 10;344(19):1434-41. doi: 10.1056/NEJM200105103441904.
- Background: PubMed 15805200Alkhiary YM, Gerstenfeld LC, Krall E, Westmore M, Sato M, Mitlak BH, Einhorn TA. Enhancement of experimental fracture-healing by systemic administration of recombinant human parathyroid hormone (PTH 1-34). J Bone Joint Surg Am. 2005 Apr;87(4):731-41. doi: 10.2106/JBJS.D.02115.
- Background: PubMed 14646773Chen H, Frankenburg EP, Goldstein SA, McCauley LK. Combination of local and systemic parathyroid hormone enhances bone regeneration. Clin Orthop Relat Res. 2003 Nov;(416):291-302. doi: 10.1097/01.blo.0000079443.64912.18.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jill Bashutski, DDS, MS principal investigator
Faculty
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Teriparatide in people with Implant, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bone Formation Rate (time frame: 10 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01279187, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2018.