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Impact of Parathyroid Hormone (PTH) on Osseous Cavity

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by:
University of Michigan
ClinicalTrials.gov Identifier:
NCT00277706
First received: January 12, 2006
Last updated: October 6, 2009
Last verified: October 2009

January 12, 2006
October 6, 2009
August 2004
July 2009   (final data collection date for primary outcome measure)
The primary objective of this pilot study is to determine the effect of Forteo (PTH) on periodontal regeneration.
Same as current
Complete list of historical versions of study NCT00277706 on ClinicalTrials.gov Archive Site
The secondary objectives are to determine the effect of PTH on parameters associated with periodontal health such as attachment level, radiographic bone density and bone height, and gingival crevicular fluid levels of bone active cytokines.
Same as current
Not Provided
Not Provided
 
Impact of Parathyroid Hormone (PTH) on Osseous Cavity
Impact of Parathyroid Hormone (1-34) on Osseous Regeneration in the Oral Cavity

Parathyroid hormone (PTH) has potent bone-building actions and has been approved for the treatment of osteoporosis as FORTEO by Eli Lilly & Co. Numerous studies have verified its effectiveness in increasing bone mass and potential for PTH to positively impact oral bone. The hypothesis of this study is that patients administered FORTEO along with periodontal (gum) surgery will respond more favorably than patients who receive placebo.

There will be 40 subjects enrolled in this study. All subjects will receive surgical treatment. 20 subjects will receive FORTEO and 20 will receive placebo. Subjects will be assigned to study group randomly. Neither the subjects nor the clinicians will know whether the subject is receiving FORTEO or placebo.

Patients will undergo routine periodontal treatment procedures including periodontal surgery. Starting from 3 days prior to surgery, all subjects will self-administer FORTEO or placebo for 6 weeks. Subjects will be trained for self-administration, a procedure similar to diabetic injections. Patients will also take Vitamin D and Calcium by mouth during this time. Study outcomes will be measured by blood collection; oral fluid sampling; oral x-ray and spine and hip bone density scan; routine periodontal examinations; and an oral health quality of life questionnaire.

Patients of both genders and all ethnicities from age 30-75 years will be included in the study. All ethnicities are eligible for entry into study. No vulnerable populations will be included. Pregnant/breast-feeding women and women of childbearing potential on no contraception will be excluded from the study. Research records will not be linkable to the research subjects. Subjects will be randomly assigned to treatment arms and identified by initials and numbers. Informed consent forms will be used to obtain consent for participation in the study from all subjects prior to enrollment. The Principal Investigator or Co-Investigator will explain the details of study involvement and give subjects ample opportunity to ask questions.

It is anticipated that patients on FORTEO will have greater regeneration with periodontal therapy as compared to control patients.

Parathyroid hormone is an endogenous hormone with potent anabolic and catabolic actions in bone. It has recently been approved for the treatment of osteoporosis and is marketed as FORTEO by Eli Lilly and Company. Numerous studies in humans have validated its use to increase bone mineral density and prevent fractures. Interest has also surfaced in its potential application in the treatment of non-osteoporotic fractures and several animal studies have supported this local application. Little is known regarding its use in treating conditions of the oral cavity, but animal studies suggest that bones of the oral cavity are responsive to the anabolic actions of PTH. Furthermore, a recent study indicated that in a canine model, PTH was effective at reversing periodontal bone loss. Studies from our laboratory indicate that patients with hyperparathyroidism (HPT) do not have an increase in periodontal disease as measured by attachment levels. In fact, in our patient population there was an increase in osseous activity in patients with HPT in the form of tori and exostoses (bony protuberances in the oral cavity). This suggests that increased circulating levels of PTH do not adversely impact the oral cavity. Furthermore, in a wound healing animal model of bone regeneration, we found that regenerating intramembranous bone was more responsive to anabolic actions of PTH than endogenous bone of the vertebrae. These studies highlight the potential for PTH to positively impact osseous healing in the oral cavity in response to periodontal therapy.

The study will be double blinded, and patients will be randomized into one of two treatment groups (FORTEO or placebo once/daily). Patients will self-administer drug on a QD schedule, and take Vitamin D and Calcium, PO, QD, for six weeks. Drug administration will begin three days prior to periodontal surgery. Subjects will be followed at post-op, week 3, week 6, month 3, month 6, month 9, and month 12 visits. Clinical effects will be measured by serum collection, gingival crevicular fluid (GCF) sampling, standard dental radiographs, oral exam including perio probing, oral health quality of life questionnaire, and DEXA scans.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
  • Bone Loss
  • Periodontitis
  • Procedure: Periodontal surgery
  • Drug: FORTEO
    parathyroid hormone; self-administration for 6 weeks
  • Drug: Placebo
    placebo; self administration for 6 weeks
  • Dietary Supplement: Vitamin D and Calcium
    PO, QD, for six weeks
  • Experimental: FORTEO
    Interventions:
    • Procedure: Periodontal surgery
    • Drug: FORTEO
    • Dietary Supplement: Vitamin D and Calcium
  • Placebo Comparator: Placebo
    Interventions:
    • Procedure: Periodontal surgery
    • Drug: Placebo
    • Dietary Supplement: Vitamin D and Calcium

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
40
July 2009
July 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age range: 30 to 75 years
  • Sex: Male and female
  • Female patients must be postmenopausal (for at least 2 years), surgically sterilized or utilizing one of the following methods of birth control throughout the trial - IUD, diaphragm, Depo-Provera, Norplant, oral contraceptive with condom or spermicidal gel/foam with a condom, or abstinence
  • Patients must be able and willing to follow study procedures and instructions
  • Patients must have read, understood and signed an informed consent form
  • Patients must have localized or generalized, advanced periodontal disease (American Dental Association Class 4)
  • Patients must present with at least 10 teeth in the functional dentition
  • Each patient must have at least one tooth with the following criteria to enter the study:

    • Periodontal probing depths of > 6 mm to < 14 mm
    • Attachment loss of > 6 mm to < 14 mm
    • Bleeding on probing

Exclusion Criteria:

  • Patients under 30 years of age
  • Female patients who are pregnant (as determined by positive urine pregnancy test at screening) or lactating, or female patients who are of childbearing potential who are not using hormonal, barrier methods of birth control or abstinence.
  • Patients who are using hormonal contraceptives must have started the method not fewer than 30 days prior to the screening examination.
  • Patients with metabolic bone diseases such as Paget's disease, hypercalcemia, vitamin D3 abnormalities or any other metabolic bone disease including osteoporosis. (If Vitamin D levels are low (> 20 ng/ml - 24 ng/ml), dietary supplementation will be initiated and levels re-evaluated after 4 weeks and reconsidered for inclusion at that time.)
  • Patients with prior radiation treatment, bone metastasis or other skeletal malignancy
  • Patients on medications that would affect bone metabolism
  • Patients with growth hormone deficiency
  • Patients with uncontrolled diabetes, sprue, inflammatory bowel disease or other disorders that would affect calcium absorption.
  • Patients who are heavy smokers (> 1 pack/day); Patients on bisphosphonates, including Fosamax
  • Patients with any form of kidney disease including kidney stones (urolithiasis and nephrolithiasis); and
  • Patients on digitalis therapy
Both
30 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00277706
2004-03
Not Provided
Not Provided
University of Michigan
Eli Lilly and Company
Principal Investigator: Laurie K McCauley, DDS, PhD Professor and Chair
University of Michigan
October 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP