The Impact of Parathyroid Hormone (PTH) on Craniofacial Osseous Regeneration in Bone

NCT ID: NCT01279187

Last Updated: 2018-02-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2015-11-30

Brief 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. 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.

Conditions

Implant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Teriparatide

Intervention Type: DRUG

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

20ug per day, self administered injection, for 7 weeks

Interventions

Teriparatide

20ug per day,via subcutaneous injection, for 7 weeks

Intervention Type: DRUG

Placebo

20ug per day, self administered injection, for 7 weeks

Intervention Type: DRUG

Other Intervention Names

Forteo; carrier

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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,
• 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,

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Jill Bashutski

Clinical Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jill Bashutski, DDS, MS

Role: PRINCIPAL_INVESTIGATOR

Faculty

Locations

Michigan Center for Oral Health Research

Ann Arbor, Michigan, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 11346808 (View on PubMed)

Alkhiary 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.

Reference Type: BACKGROUND

PMID: 15805200 (View on PubMed)

Chen 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.

Reference Type: BACKGROUND

PMID: 14646773 (View on PubMed)

Other Identifiers

HUM00042770

Identifier Type: -

Identifier Source: org_study_id