Teriparatide as a Chondroregenerative Therapy in OA

NCT ID: NCT03072147

Last Updated: 2023-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-01
• Study Completion Date: 2022-09-30

Brief Summary

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.

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).

Conditions

Knee Osteoarthritis; Cartilage Degeneration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Teriparatide

Intervention Type: DRUG

20 mcg of teriparatide injected in thigh or abdomen once a day for 24 weeks.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

20 mcg of saline injected in thigh or abdomen once a day for 24 weeks.

Interventions

Teriparatide

20 mcg of teriparatide injected in thigh or abdomen once a day for 24 weeks.

Intervention Type: DRUG

Placebo

20 mcg of saline injected in thigh or abdomen once a day for 24 weeks.

Intervention Type: DRUG

Other Intervention Names

Group 1; Forteo; Group 2

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: collaborator

Milton S. Hershey Medical Center

OTHER

Sponsor Role: collaborator

Christopher Ritchlin

OTHER

Sponsor Role: lead

Responsible Party

Christopher Ritchlin

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Michael Zuscik, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Emily Carmody, MD

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Christopher Ritchlin, MD

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Locations

URMC Orthopaedics, Clinton Crossings Building D

Rochester, New York, United States

Countries

United States

Other Identifiers

Forteo 65996

Identifier Type: -

Identifier Source: org_study_id