Teriparatide as a Chondroregenerative Therapy in OA

Knee Osteoarthritis Clinical Trial

Official title:

Evaluating Teriparatide as a Chondroregenerative Therapy in Human Osteoarthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03072147
• Other study ID #: Forteo 65996
• Status: Completed
• Phase: Phase 2
• Start date: May 1, 2017
• Est. completion date: September 30, 2022

Study information

• Verified date: May 2023
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: September 30, 2022
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Cartilage Degeneration
• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Teriparatide
20 mcg of teriparatide injected in thigh or abdomen once a day for 24 weeks.
• Placebo
20 mcg of saline injected in thigh or abdomen once a day for 24 weeks.

Locations

Country	Name	City	State
United States	URMC Orthopaedics, Clinton Crossings Building D	Rochester	New York

Sponsors (5)

Lead Sponsor	Collaborator
Christopher Ritchlin	Duke University, Eli Lilly and Company, Milton S. Hershey Medical Center, University of Rochester

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Flexed Knee Radiograph	Interpreted using fractal signature analysis.	Change from Baseline through study completion (baseline, 24 weeks, 48 weeks), an average of one year.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.