Back to resultsTeriparatide as a Chondroregenerative Therapy in OA
Primary Purpose
Knee Osteoarthritis, Cartilage Degeneration
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Teriparatide
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Knee Osteoarthritis
Eligibility Criteria
Inclusion Criteria:
- male or female 40 to 60 years old.
- radiographic evidence of Kellgren-Lawrence score (K-L score) grade I-II OA in the affected knee
- unilateral symptomatic knee OA
- willingness to forgo potential standard of care treatments (hyaluronic acid and cortisol injections) for knee pain for the duration of the study
- body Mass Index of ≤40
- normal screening vitamin D levels (≥20 and ≤100 mg/ml)
- normal screening serum calcium level (8.5- 10.2 mg/dL)
- a negative screening serum pregnancy test for premenopausal women
Exclusion Criteria:
- history of primary hyperparathyroidism disease, hypercalcemia, or persistently abnormal intake PTH levels (≥10 or ≤65 pg/ml)
- history of musculoskeletal malignancy or solid organ carcinoma
- active renal disease defined by a creatinine clearance of <35 or history of kidney stones within the past year
- use of anticonvulsant or digoxin therapy
- inflammatory disease (bowel disease, spondylitis, lupus, fibromyalgia, psoriasis, rheumatoid arthritis, etc)
- current or past treatment with teriparatide
- use of immunosuppressants
- 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)
- dementia, cognitive impairment or other factors that referring provider feels would prevent ability to obtain informed consent and/or follow study protocol
- pregnancy or intent to become pregnant in the two and a half years following enrollment
- women who are currently breastfeeding
- Paget's disease
- osteoporosis diagnosis by DXA in medical history (T-score less than or equal to -2.5)
- reliance on assistive walking devices (canes, walkers, braces, etc.)
- participation in concurrent clinical studies involving investigational medications
Sites / Locations
- URMC Orthopaedics, Clinton Crossings Building D
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Group 1- Treatment
Group 2- Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Knee MRI
Analysis using Regional Cartilage Volume Segmentation
Secondary Outcome Measures
Flexed Knee Radiograph
Interpreted using fractal signature analysis.
Urine Biomarker Analysis
Analyzed immediately via enzyme-linked immunosorbent assay (ELISA) to quantify the following biomarker: urinary type II collagen
Serum Biomarker Analysis
Analyzed immediately via enzyme-linked immunosorbent assay (ELISA) to quantify the following biomarker: serum type II collagen degradation neoepitope.
GAITRite
Change in gait pre- and post-treatment analyzed using the GAITRite walking test.
Timed up and go
Change in gait pre- and post-treatment analyzed using the timed-up-and-go (TUG) test.
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.
PROMIS Depression
The Depression scale from the Patient-Reported Outcomes Measurement Information System (PROMIS) measures measures subjective changes in mood, pre- and post-treatment.
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.
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.
Full Information
NCT ID
NCT03072147
First Posted
February 21, 2017
Last Updated
May 10, 2023
Sponsor
Christopher Ritchlin
Collaborators
Eli Lilly and Company, University of Rochester, Duke University, Milton S. Hershey Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03072147
Brief Title
Teriparatide as a Chondroregenerative Therapy in OA
Official Title
Evaluating Teriparatide as a Chondroregenerative Therapy in Human Osteoarthritis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
May 1, 2017 (Actual)
Primary Completion Date
September 30, 2022 (Actual)
Study Completion Date
September 30, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Christopher Ritchlin
Collaborators
Eli Lilly and Company, University of Rochester, Duke University, Milton S. Hershey Medical Center
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Knee Osteoarthritis, Cartilage Degeneration
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
This is a prospective, randomized, placebo controlled, double blinded study. Interim results will determine if there is a crossover.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Researchers, providers, and subjects will be blinded to treatment group so that outcomes will not be influenced by expectations about the experimental treatment.
Allocation
Randomized
Enrollment
76 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1- Treatment
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Group 2- Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Teriparatide
Other Intervention Name(s)
Group 1, Forteo
Intervention Description
20 mcg of teriparatide injected in thigh or abdomen once a day for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Group 2
Intervention Description
20 mcg of saline injected in thigh or abdomen once a day for 24 weeks.
Primary Outcome Measure Information:
Title
Knee MRI
Description
Analysis using Regional Cartilage Volume Segmentation
Time Frame
Change from Baseline through study completion (baseline, 24 weeks, 48 weeks), an average of one year.
Secondary Outcome Measure Information:
Title
Flexed Knee Radiograph
Description
Interpreted using fractal signature analysis.
Time Frame
Change from Baseline through study completion (baseline, 24 weeks, 48 weeks), an average of one year.
Title
Urine Biomarker Analysis
Description
Analyzed immediately via enzyme-linked immunosorbent assay (ELISA) to quantify the following biomarker: urinary type II collagen
Time Frame
Change from Baseline through study completion (baseline, 12 weeks, 24 weeks, 48 weeks), an average of one year.
Title
Serum Biomarker Analysis
Description
Analyzed immediately via enzyme-linked immunosorbent assay (ELISA) to quantify the following biomarker: serum type II collagen degradation neoepitope.
Time Frame
Change from Baseline through study completion (baseline, 12 weeks, 24 weeks, 48 weeks), an average of one year.
Title
GAITRite
Description
Change in gait pre- and post-treatment analyzed using the GAITRite walking test.
Time Frame
Change from Baseline through study completion (baseline, 12 weeks, 24 weeks, 48 weeks), an average of one year.
Title
Timed up and go
Description
Change in gait pre- and post-treatment analyzed using the timed-up-and-go (TUG) test.
Time Frame
Change from Baseline through study completion (baseline, 12 weeks, 24 weeks, 48 weeks), an average of one year.
Title
WOMAC 3.1
Description
The Western Ontario and McMaster Universities Arthritis Index (WOMAC 3.1) measures pre- and post-treatment changes in subjective pain and functionality.
Time Frame
Change from Baseline through study completion (baseline, 12 weeks, 24 weeks, 48 weeks), an average of one year.
Title
PROMIS Depression
Description
The Depression scale from the Patient-Reported Outcomes Measurement Information System (PROMIS) measures measures subjective changes in mood, pre- and post-treatment.
Time Frame
Change from Baseline through study completion (baseline, 4 weeks, 12 weeks, 24 weeks, 48 weeks), an average of one year.
Title
PROMIS Pain Interference
Description
The Pain Interference scale from the Patient-Reported Outcomes Measurement Information System (PROMIS) measures subjective changes in pain distress, pre- and post-treatment.
Time Frame
Change from Baseline through study completion (baseline, 4 weeks, 12 weeks, 24 weeks, 48 weeks), an average of one year.
Title
PROMIS Physical Function
Description
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.
Time Frame
Change from Baseline through study completion (baseline, 4 weeks, 12 weeks, 24 weeks, 48 weeks), an average of one year.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
male or female 40 to 60 years old.
radiographic evidence of Kellgren-Lawrence score (K-L score) grade I-II OA in the affected knee
unilateral symptomatic knee OA
willingness to forgo potential standard of care treatments (hyaluronic acid and cortisol injections) for knee pain for the duration of the study
body Mass Index of ≤40
normal screening vitamin D levels (≥20 and ≤100 mg/ml)
normal screening serum calcium level (8.5- 10.2 mg/dL)
a negative screening serum pregnancy test for premenopausal women
Exclusion Criteria:
history of primary hyperparathyroidism disease, hypercalcemia, or persistently abnormal intake PTH levels (≥10 or ≤65 pg/ml)
history of musculoskeletal malignancy or solid organ carcinoma
active renal disease defined by a creatinine clearance of <35 or history of kidney stones within the past year
use of anticonvulsant or digoxin therapy
inflammatory disease (bowel disease, spondylitis, lupus, fibromyalgia, psoriasis, rheumatoid arthritis, etc)
current or past treatment with teriparatide
use of immunosuppressants
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)
dementia, cognitive impairment or other factors that referring provider feels would prevent ability to obtain informed consent and/or follow study protocol
pregnancy or intent to become pregnant in the two and a half years following enrollment
women who are currently breastfeeding
Paget's disease
osteoporosis diagnosis by DXA in medical history (T-score less than or equal to -2.5)
reliance on assistive walking devices (canes, walkers, braces, etc.)
participation in concurrent clinical studies involving investigational medications
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Zuscik, PhD
Organizational Affiliation
University of Rochester
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Emily Carmody, MD
Organizational Affiliation
University of Rochester
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Christopher Ritchlin, MD
Organizational Affiliation
University of Rochester
Official's Role
Principal Investigator
Facility Information:
Facility Name
URMC Orthopaedics, Clinton Crossings Building D
City
Rochester
State/Province
New York
ZIP/Postal Code
14618
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Teriparatide as a Chondroregenerative Therapy in OA
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