The Impact of Parathyroid Hormone (PTH) on Craniofacial Osseous Regeneration in Bone - Full Text View

Purpose

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.

Condition	Intervention	Phase
Implant	Drug: Teriparatide Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	The Impact of Parathyroid Hormone (PTH) on Craniofacial Osseous Regeneration in Bone

Resource links provided by NLM:

Drug Information available for: Parathyroid Hormone Teriparatide Teriparatide acetate

U.S. FDA Resources

Further study details as provided by University of Michigan:

Primary Outcome Measures:

Bone formation rate [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

bone turnover [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
include serum and GCF parameters of bone turnover, cellular parameters of PTH action (i.e. numbers of osteoblasts, osteoclasts, apoptotic osteoblasts) along with derived outcomes such as; the correlation of systemic serum PINP and bone structure and dynamic indices at baseline; changes in systemic PINP as correlated with local bone formation rates in the mandible; and whether numbers of apoptotic osteoblasts correlate with bone formation rates.

Estimated Enrollment:	30
Study Start Date:	February 2011
Estimated Study Completion Date:	July 2015
Estimated Primary Completion Date:	July 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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.	Drug: Teriparatide 20ug per day,via subcutaneous injection, for 7 weeks Other Name: Forteo
Placebo Comparator: 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.	Drug: Placebo 20ug per day, self administered injection, for 7 weeks Other Name: carrier

Arms

Assigned Interventions

Experimental: 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.

Drug: Teriparatide

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

Other Name: Forteo

Placebo Comparator: 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.

Drug: Placebo

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

Other Name: carrier

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.

Eligibility

Ages Eligible for Study:	30 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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,

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01279187

Contacts

Contact: Jan Riggs, BS	734-998-1468	mcohrclinicalresearch@umich.edu
Contact: Marie Ringbloom	734-998-1435	mcohrclinicalresearch@umich.edu

Locations

United States, Michigan
Michigan Center for Oral Health Research	Recruiting
Ann Arbor, Michigan, United States, 48106
Contact: Jan Riggs, BS 734-998-1468 mcohrclinicalresearch@umich.edu
Contact: Marie Ringbloom 734-998-1435 mcohrclinicalresearch@umich.edu
Principal Investigator: Jill Bashutski, DDS, MS

Sponsors and Collaborators

University of Michigan

Eli Lilly and Company

Investigators

Principal Investigator:

Jill Bashutski, DDS, MS

Faculty

More Information

Publications:

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.

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.

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.

Responsible Party:	Jill Bashutski, Clinical Assistant Professor, University of Michigan
ClinicalTrials.gov Identifier:	NCT01279187 History of Changes
Other Study ID Numbers:	HUM00042770
Study First Received:	January 18, 2011
Last Updated:	December 19, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Michigan:

dental
implant

Additional relevant MeSH terms:

Hormones
Teriparatide
Hormones, Hormone Substitutes, and Hormone Antagonists

Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on May 16, 2013