Forteo Trial on Idiopathic Osteoporosis in Premenopausal Women
Information source: Columbia University
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Adult Idiopathic Generalized Osteoporosis
Intervention: Teriparatide (Drug); Saline Placebo (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Elizabeth Shane Official(s) and/or principal investigator(s): Elizabeth Shane, MD, Principal Investigator, Affiliation: Columbia University Adi Cohen, MD, Study Director, Affiliation: Columbia University Emily M Stein, MD, Study Director, Affiliation: Columbia University
Overall contact: Mariana Bucovsky, BA, Phone: 212-305-7225, Email: mb3523@columbia.edu
Summary
Idiopathic osteoporosis (IOP) is defined as osteoporosis that affects young, otherwise
completely healthy individuals with no secondary cause of bone loss. In the course of our
prior research with premenopausal women with IOP, the investigators have shown that women
with IOP have low areal bone mineral density (aBMD) at the spine, hip and forearm compared
to normal women. Additionally, using noninvasive high resolution imaging of the central and
peripheral skeleton and detailed analyses of transiliac crest bone biopsies, the
investigators identified several features of bone quality in premenopausal women with IOP.
There is currently no FDAapproved therapy for IOP in premenopausal women. However,
teriparatide (Forteo) has been shown to improve bone mass and microarchitecture in
postmenopausal women and is approved for men with primary or idiopathic osteoporosis, as
well as men, premenopausal and postmenopausal women with glucocorticoid-induced
osteoporosis. Because IOP in premenopausal women is an orphan disease, with an estimated
prevalence of about 113,000 in the United States, pharmaceutical companies are unlikely to
support development of therapies for this indication. Therefore the major objective of this
protocol is to establish the safety and efficacy of teriparatide in premenopausal women with
IOP in a phase 2 clinical trial. All subjects will receive teriparatide as part of the
study, but a randomly selected group of patients (10) will receive one year of placebo
injections first before starting their two years of treatment. The remainder of subjects
(30) will receive active drug only for two years.
Clinical Details
Official title: Randomized Controlled Trial of Teriparatide for the Treatment of Idiopathic Osteoporosis in Premenopausal Women
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Change in lumbar spine bone mineral density (LS-BMD)
Detailed description:
Funding Source: FDA-OOPD
Osteoporosis is a skeletal disorder characterized by reduced bone strength that predisposes
to an increased risk of fracture. Osteoporosis affects postmenopausal women and elderly men
and is very unusual in healthy individuals under age 50. Moreover, more than 90% of young
men and premenopausal women with osteoporosis have a secondary cause of bone lose, such as
an underlying disorder (e. g., hypogonadism) or a medication exposure (e. g., glucocorticoids,
antiepileptic drugs), that either interfered with acquisition of peak bone mass or caused
excessive bone loss thereafter. Idiopathic osteoporosis (IOP) is defined as osteoporosis
that affects young, otherwise completely healthy individuals with intact gonadal function
and no secondary cause of bone loss. First described by Fuller Albright in 1944, IOP is an
uncommon condition with an estimated annual incidence of 0. 4 cases per 100,0003. IOP
predominantly affects Caucasians, who generally present in their mid-30s with one more low
trauma fractures.
In the course of an NIH-funded study of premenopausal women with IOP (R01 AR49896, IRB
AAAA9245), the investigators have shown that women with IOP have low areal bone mineral
density (aBMD) at the spine, hip and forearm compared to normal women. Additionally, using
noninvasive high resolution imaging of the central and peripheral skeleton and detailed
analyses of transiliac crest bone biopsies, the investigators identified several distinctive
and consistent features of bone quality in premenopausal women with IOP: thin cortices,
lower trabecular volumetric bone mineral density (vBMD), fewer trabecular plates, fewer and
longer trabecular rods, decreased connectivity between rods and plates, lower mineralization
density and lower estimated stiffness of cancellous bone. Bone remodeling and biochemical
indices of mineral metabolism did not differ between IOP subjects and controls.
Although not every woman with IOP requires pharmacologic intervention, many have sustained
multiple low-trauma fractures or have extremely low bone mineral density (BMD). There is
currently no FDA-approved therapy for IOP in premenopausal women, therefore a safe and
effective therapy is urgently needed. Bisphosphonates are one therapeutic option but the
associated gains in BMD are primarily due to reduction in the remodeling space and increased
mineralization of bone rather than improvements in microarchitecture, an important
consideration as microarchitectural deficits are a consistent feature of IOP in
premenopausal women, while remodeling activity is most commonly normal or low. Furthermore,
potential teratogenic effects limit the safety of bisphosphonates in premenopausal women.
However, anabolic therapy with human recombinant parathyroid hormone 1-34, hPTH(1-34) or
teriparatide (TPTD), terms which will be used interchangeably in this proposal, has been
shown to improve bone mass and microarchitecture in postmenopausal women and is approved for
men with primary or idiopathic osteoporosis, as well as men, premenopausal and
postmenopausal women with glucocorticoid-induced osteoporosis. TPTD, on the other hand,
increases bone formation and BMD, while improving microarchitecture and strength. Moreover,
TPTD has been shown to increase BMD in men with IOP, in premenopausal women with
glucocorticoid-induced osteoporosis (GIOP)and to prevent bone loss in premenopausal women
with nafarelin-induced acute estrogen deficiency. Although there have been no studies
evaluating TPTD in estrogen-replete premenopausal women with IOP, data from studies of
hPTH(1-34) in postmenopausal women on estrogen are relevant to this proposal. These studies
found increased aBMD at the LS and of lesser magnitude at the hip, as well as major
reductions in vertebral fracture. Also important, BMD remained stable in postmenopausal
women on estrogen followed for two years after TPTD discontinuation. Lane et al. reported
similar results in postmenopausal women with GIOP on estrogen. These two studies suggest
that in estrogen-replete premenopausal women with IOP, increases in bone mass resulting from
TPTD will be sustained after the course of therapy is completed.
The major objective of this protocol is a therapeutic one, namely to establish the safety
and efficacy of TPTD in premenopausal women with IOP in a phase 2 clinical trial. The
investigators hypothesize that anabolic therapy with teriparatide will improve areal and
vBMD in premenopausal women with IOP. The investigators also hypothesize that teriparatide
will restore abnormal microarchitecture toward normal and improve other aspects of bone
quality in premenopausal women with IOP. The primary aim of this research study will be to
establish the efficacy and safety of 6 months of teriparatide versus placebo in
premenopausal women with IOP. Our secondary aim is to determine the extent to which 12 and
24 months of teriparatide improves areal and volumetric BMD, bone microarchitecture and
stiffness compared to baseline measures in premenopausal women with IOP. This study will
have high impact on clinical practice as it pertains to the management of premenopausal
women with IOP. This study is exploratory and will not support any new labeling claims for
Forteo in the premenopausal patient population.
Eligibility
Minimum age: 20 Years.
Maximum age: 45 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Premenopausal women, aged 20-45, with regular menses and no historical or biochemical
secondary cause of osteoporosis.
- Documented adult fractures judged to be low-trauma.
- Must be willing to use effective contraception throughout the period of study drug
administration.
Inclusion criteria vary slightly based on age category:
- Premenopausal women ages 20-35 years must have at least one major osteoporotic
fracture (excluding fractures of fingers, toes and face) AND low Bone Mineral
Density(BMD).
- Premenopausal women above the age of 35 years should have a history of fracture
AND/OR low BMD.
Exclusion Criteria:
- History of any condition that increases the risk of osteosarcoma
- Early follicular phase serum
- Disorders of mineral metabolism
- Suspicion of osteomalacia
- Vitamin D deficiency
- Pregnancy or lactation within past 12 months
- Prolonged amenorrhea (> 6 months) during reproductive years (except pregnancy or
lactation)
- Prior eating disorder
- Malignancy, except cured basal or squamous cell skin carcinoma
- Endocrinopathy: new onset untreated hyperthyroidism, hypothyroidism, Cushing's
syndrome, prolactinoma
- Renal insufficiency
- Liver disease
- Intestinal disorders
- History/current GCs, anticonvulsants, anticoagulants, methotrexate, depot
progesterone, GnRH agonists
- Oral glucocorticoid use (subject will not be excluded if used dose equivalent to less
than prednisone 5 mg for <3 months).
- Current anticoagulant use or low molecular weight
- Depo Provera use (subjects will not be excluded if used at age>20, >5 years ago)
- Drugs for osteoporosis (raloxifene, bisphosphonates, denosumab, calcitonin, TPTD).
Subjects who discontinue these medications will be eligible 3 months after stopping
raloxifene or calcitonin, 12 months after stopping alendronate, risedronate,
ibandronate, or pamidronate and 18 months after stopping denosumab. Subjects with
prior use of zoledronate may be eligible if received only one dose >4 years ago.
Total bisphosphonate exposure must be < 1 year. Subjects who have taken TPTD in the
past will not be eligible unless used for <3 months, > 2 years ago.
Locations and Contacts
Mariana Bucovsky, BA, Phone: 212-305-7225, Email: mb3523@columbia.edu
Creighton University, Omaha, Nebraska 68131, United States; Recruiting Phone: 402-280-4470 Robert Recker, MD, Principal Investigator Joan Lappe, MD, Sub-Investigator
Columbia University Medical Center, New York, New York 10032, United States; Recruiting Phone: 212-305-7225 Elizabeth Shane, MD, Principal Investigator Adi Cohen, MD, Sub-Investigator Emily M Stein, MD, Sub-Investigator
Additional Information
Columbia University, Dept of Medicine, Division of Endocrinology website
Starting date: January 2012
Last updated: April 6, 2015
|