Teriparatide as a Chondroregenerative Therapy in OA

Evaluating Teriparatide as a Chondroregenerative Therapy in Human Osteoarthritis

The purpose of this study is to evaluate teriparatide (TP) as a chondroregenerative therapy for human knee osteoarthritis (OA). The central hypothesis to be tested is that TP supports structural modification of the joint and improves biomarker, functional and patient-reported measures of knee OA.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis; Cartilage Degeneration
• Intervention / Treatment: Drug: Teriparatide; Drug: Placebo

Detailed Description

This is a prospective, randomized, placebo controlled, double blinded, crossover study. The investigators will identify, recruit and enroll 80 subjects with symptomatic, unilateral medial compartment knee OA. Enrolled subjects will be randomized into equal TP (in the FDA approved form, Forteo) or placebo arms of 40 subjects each (includes allowance for a 25% dropout rate with no replacements). All subjects will be treated for 24 weeks, then followed for an additional 24 weeks to assess the durability of any observed effects. The trial incorporates a crossover design, based on interim analysis of the 24 week outcome data after every subject has completed the 24 week treatment period. If positive effects on structural and/or biomarker measures are apparent from the interim analysis, placebo treated subjects will be offered TP (in the FDA approved form, Forteo) and followed for an additional 24 weeks. If the placebo subjects who choose to participate in the crossover treatment have not yet completed the 48 week visit, it will not occur. These subjects will begin the crossover portion 24 week treatment and monitoring period when they receive the TP pens (in the FDA approved form, Forteo).

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14618
      • URMC Orthopaedics, Clinton Crossings Building D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 58 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. male or female 40 to 60 years old.
2. radiographic evidence of Kellgren-Lawrence score (K-L score) grade I-II OA in the affected knee
3. unilateral symptomatic knee OA
4. willingness to forgo potential standard of care treatments (hyaluronic acid and cortisol injections) for knee pain for the duration of the study
5. body Mass Index of ≤40
6. normal screening vitamin D levels (≥20 and ≤100 mg/ml)
7. normal screening serum calcium level (8.5- 10.2 mg/dL)
8. a negative screening serum pregnancy test for premenopausal women

Exclusion Criteria:

1. history of primary hyperparathyroidism disease, hypercalcemia, or persistently abnormal intake PTH levels (≥10 or ≤65 pg/ml)
2. history of musculoskeletal malignancy or solid organ carcinoma
3. active renal disease defined by a creatinine clearance of <35 or history of kidney stones within the past year
4. use of anticonvulsant or digoxin therapy
5. inflammatory disease (bowel disease, spondylitis, lupus, fibromyalgia, psoriasis, rheumatoid arthritis, etc)
6. current or past treatment with teriparatide
7. use of immunosuppressants
8. severe claustrophobia, retained eye or skull metal fragments, metal hardware in or around the affected knee or other standard contraindications to MRI (cochlear implants, pacemakers)
9. dementia, cognitive impairment or other factors that referring provider feels would prevent ability to obtain informed consent and/or follow study protocol
10. pregnancy or intent to become pregnant in the two and a half years following enrollment
11. women who are currently breastfeeding
12. Paget's disease
13. osteoporosis diagnosis by DXA in medical history (T-score less than or equal to -2.5)
14. reliance on assistive walking devices (canes, walkers, braces, etc.)
15. participation in concurrent clinical studies involving investigational medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1- Treatment; 20 mcg dosage amounts of teriparatide, in the FDA approved form Forteo, manufactured by Lilly, LLC, are loaded into a 2.4 ml prefilled delivery device (multi injection pen) that administers 28 equal doses as subcutaneous injections in the thigh or abdominal wall. Subjects will inject themselves once a day for 24 weeks.	Drug: Teriparatide; 20 mcg of teriparatide injected in thigh or abdomen once a day for 24 weeks.; Other Names: Forteo; Group 1
Placebo Comparator: Group 2- Placebo; Saline placebo is packaged by the manufacturer (Lilly, LLC) in the same 2.4 ml injection pen that is used for teriparatide; it will provide 28 doses of placebo. Subjects will inject themselves once a day for 24 weeks.	Drug: Placebo; 20 mcg of saline injected in thigh or abdomen once a day for 24 weeks.; Other Names: Group 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee MRI	Analysis using Regional Cartilage Volume Segmentation	Change from Baseline through study completion (baseline, 24 weeks, 48 weeks), an average of one year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flexed Knee Radiograph	Interpreted using fractal signature analysis.	Change from Baseline through study completion (baseline, 24 weeks, 48 weeks), an average of one year.
Urine Biomarker Analysis	Analyzed immediately via enzyme-linked immunosorbent assay (ELISA) to quantify the following biomarker: urinary type II collagen	Change from Baseline through study completion (baseline, 12 weeks, 24 weeks, 48 weeks), an average of one year.
Serum Biomarker Analysis	Analyzed immediately via enzyme-linked immunosorbent assay (ELISA) to quantify the following biomarker: serum type II collagen degradation neoepitope.	Change from Baseline through study completion (baseline, 12 weeks, 24 weeks, 48 weeks), an average of one year.
GAITRite	Change in gait pre- and post-treatment analyzed using the GAITRite walking test.	Change from Baseline through study completion (baseline, 12 weeks, 24 weeks, 48 weeks), an average of one year.
Timed up and go	Change in gait pre- and post-treatment analyzed using the timed-up-and-go (TUG) test.	Change from Baseline through study completion (baseline, 12 weeks, 24 weeks, 48 weeks), an average of one year.
WOMAC 3.1	The Western Ontario and McMaster Universities Arthritis Index (WOMAC 3.1) measures pre- and post-treatment changes in subjective pain and functionality.	Change from Baseline through study completion (baseline, 12 weeks, 24 weeks, 48 weeks), an average of one year.
PROMIS Depression	The Depression scale from the Patient-Reported Outcomes Measurement Information System (PROMIS) measures measures subjective changes in mood, pre- and post-treatment.	Change from Baseline through study completion (baseline, 4 weeks, 12 weeks, 24 weeks, 48 weeks), an average of one year.
PROMIS Pain Interference	The Pain Interference scale from the Patient-Reported Outcomes Measurement Information System (PROMIS) measures subjective changes in pain distress, pre- and post-treatment.	Change from Baseline through study completion (baseline, 4 weeks, 12 weeks, 24 weeks, 48 weeks), an average of one year.
PROMIS Physical Function	Physical function scale from the Patient-Reported Outcomes Measurement Information System (PROMIS) measures subjective changes in mobility and activities of daily living, pre- and post-treatment.	Change from Baseline through study completion (baseline, 4 weeks, 12 weeks, 24 weeks, 48 weeks), an average of one year.

Collaborators and Investigators

• Sponsor: Christopher Ritchlin
• Collaborators: Eli Lilly and Company; Duke University; Milton S. Hershey Medical Center; University of Rochester
• Investigators: Principal Investigator: Michael Zuscik, PhD, University of Rochester; Principal Investigator: Emily Carmody, MD, University of Rochester; Principal Investigator: Christopher Ritchlin, MD, University of Rochester

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: February 21, 2017
• First Submitted That Met QC Criteria: March 1, 2017
• First Posted (Actual): March 7, 2017

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Teriparatide
• Other Study ID Numbers: Forteo 65996

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes