Impact of Parathyroid Hormone (PTH) on Osseous Cavity
Information source: University of Michigan
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Bone Loss; Periodontitis
Intervention: Periodontal surgery (Procedure); FORTEO (Drug); Placebo (Drug); Vitamin D and Calcium (Dietary Supplement)
Phase: Phase 1
Status: Completed
Sponsored by: University of Michigan Official(s) and/or principal investigator(s): Laurie K McCauley, DDS, PhD, Principal Investigator, Affiliation: Professor and Chair
Summary
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.
Clinical Details
Official title: Impact of Parathyroid Hormone (1-34) on Osseous Regeneration in the Oral Cavity
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Primary outcome: The primary objective of this pilot study is to determine the effect of Forteo (PTH) on periodontal regeneration.
Secondary outcome: 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.
Detailed description:
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.
Eligibility
Minimum age: 30 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
Michigan Center for Oral Health Research, Ann Arbor, Michigan 48106, United States
Additional Information
Starting date: August 2004
Last updated: October 6, 2009
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