Clinical trial NCT03217513: Knee Osteoarthritis Outcome Measures in Arthritic Patients With Osteoporosis
Official title: Pilot Study to Evaluate Knee Osteoarthritis Outcome Measures in Arthritic Patients Prescribed Forteo or Prolia for Osteoporosis
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Osteoporosis
Knee Osteoarthritis
Keywords: osteoporosis
osteoarthritis
knee
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2017-07-14
Enrollment: 0
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients that are evaluated, treated, and followed by the study investigator

Brief summary: The purpose of this study is to generate proof of concept human data by evaluating osteoarthritis outcome measures in arthritic patients that are prescribed Forteo® as the standard of care to treat their primary diagnosis of osteoporosis.

Detailed description: The traditional treatment paradigm for osteoarthritis (OA) involves palliative strategies focused on pain management and joint replacement. The longstanding inability to develop disease-modifying therapies that can rejuvenate joint cartilage is a great unmet need considering that diarthrodial and spinal OA is the most prevalent disease in the US, equal in numbers to the next top 4 disorders combined (heart, pulmonary, mental health and diabetic conditions) (CDC, 2009). Thus, the development of an effective remittive treatment for OA is a vital public health initiative with potential for tremendous impact. Our long-term research objective is to test a radically different strategy for treatment of OA that is based on findings recently published in Science Translational Medicine (Sampson et al., 2011) that identified human parathyroid hormone1-34 (teriparatide) as a chondroregenerative agent in a murine model of OA. Suggesting a parallel effect in human OA, data mined from the NIH-sponsored OA Initiative revealed improved WOMAC knee function scores in arthritic subjects coincidentally prescribed teriparatide (trade name: Forteo®) to treat osteoporosis. These preclinical and human data provide compelling rationale to study Forteo® as a novel OA therapy directed at improving joint structure and function. The central aim of our overall research program is to challenge the paradigm that cartilage loss in OA is irreversible. Thus, our long-term programmatic goal is to test Forteo® as the first and only disease-modifying treatment for OA with potential to rapidly impact clinical care. To achieve this, we have been developing a clinical trial where subjects with medial compartment Kellgren Lawrence (K-L) stage II-III knee OA will receive either Forteo® or Prolia® (a brand of denosumab) for two years. Disease progression will be assessed via structural, biomarker and functional outcomes at various time points out to 24 months post-initiation of therapy. Since Forteo® is a widely used therapeutic in patients with osteoporosis (OP)-related severe bone loss, we propose to examine OA outcomes in OP patients with concomitant knee OA. This pilot study described here that tests the hypothesis that patients with unilateral or bilateral knee OA (Kellgren-Lawrence grade II-III) that are prescribed Forteo® to treat their primary diagnosis of OP will demonstrate improved physical function (Timed-Up-And-Go), improved patient-reported outcomes (PROMIS 12a, v1.0), and increased blood levels in the cartilage anabolic marker type II collagen C-propeptide. Completion of this proposed experimental design would provide critical proof-of-concept preliminary data supporting the use of biomarkers, physical function testing and questionnaire-based functional assessment to study OA in patients.

Eligibility criteria: INCLUSION CRITERIA:

* Age: 40-80 years (inclusive)
* Gender: male or female (non-pregnant)
* Fluent in written and spoken English
* Patients capable of giving informed consent
* Primary diagnosis of osteoporosis that will be treated with either Forteo® to induce bone anabolism or Prolia® by the study investigator as part of patient's standard of care treatment
* Symptomatic, medial compartment knee OA with a Kellgren-Lawrence (K-L) score between II-III (documented in the medical record by previously collected knee series radiography). Radiographs to be performed within past two years.

EXCLUSION CRITERIA:

* Age \< 40 or \>80 years
* Cognitive impairment
* Pregnancy
* Non-English speaking persons
* History of hyperparathyroidism, hypercalcemia, current/recent renal stones, or malignancy
* Depression (currently taking home medication)
* History of inflammatory disease (colitis, rheumatoid arthritis, psoriasis, lupus, scleroderma, spondylitis)
* Use of immunosuppressants, chemotherapy, or radiotherapy
* BMI, angular deformity and K-L score of the contralateral knee (if the OA is bilateral) will be noted as covariates

Primary outcomes:
measure: Blood levels
timeFrame: 2 years
Secondary outcomes:
measure: Urine levels
timeFrame: 2 years
measure: Physical function
timeFrame: 2 years
measure: Patient reported outcomes
timeFrame: 2 years
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
Study officials:
affiliation: Milton S. Hershey Medical Center
name: Edward J Fox, M.D.
role: PRINCIPAL_INVESTIGATOR
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