Osteoarthritis, DegenerativePhase 1/2PLUS+OANCT02034409
A Pilot Trial to Assess Low-Intensity Ultrasound in Osteoarthritis
A Phase 1/2 study testing Pulsed Low Intensity Ultrasound in people with Osteoarthritis, Degenerative, run by VA Office of Research and Development at 3 sites in United States.
Trial summary
The purpose of this exploratory trial is to investigate whether PLIUS is potentially effective as a disease and symptom modifying intervention in patients with early knee OA. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Osteoarthritis, Degenerative
- What is being tested?
- Pulsed Low Intensity Ultrasound
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 3 sitesUnited States
- Study dates
- 22 May 2015to 30 Sep 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 40 years of age or older, and a US Military Veteran
- Clinical symptoms of osteoarthritis for at least 6 months
- Pain in the index knee on motion or weight bearing for the majority of days during the month before screening
- Clinical diagnosis of primary osteoarthritis of the knee based on clinical and radiographic criteria
- American Rheumatism Association Functional Class I, II, or III
- Females of childbearing potential must be willing to use a reliable form of medically acceptable contraception
Who cannot join
- Concurrent medical/arthritis condition(s), or any other illness per the opinion of the investigator, that could interfere with the evaluation of pain or efficacy
- Spine or hip pain of significant magnitude
- History of significant ligament or meniscal injury of the index joint requiring surgical repair
- Arthroscopy of the index knee within 6 months of study entry
- Unable to undergo MRI of the knee
- Pregnancy or lactation
Show all 14Show fewer
- Corticosteroid treatment within 1 to 3 months prior to study entry
- Intra-articular injection of hyaluronic acid or congeners to the index knee within 6 months of study entry
- Use of excluded therapy(ies) prior to study entry
- Use of disease modifying anti-rheumatic medications and chronic tetracycline or its derivatives
- Exposure to glucosamine, chondroitin sulfate, or any other investigational treatment, within 1 month of study entry
- Use of any medical therapy, complementary or alternative regimens for the treatment of osteoarthritis within 7 days prior to study entry
- Initiation of physical therapy or muscle conditioning program to the lower extremities within 2 months within 2 months prior to study entry
- Unlikely to comply with study requirements
Trial locations and contacts
3 sites in 1 country.
United States3 sites
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
Dallas, Texas, 75216
VA Salt Lake City Health Care System, Salt Lake City, UT
Salt Lake City, Utah, 84148
VA San Diego Healthcare System, San Diego, CA
San Diego, California, 92161
About this study
The purpose of this exploratory trial is to investigate whether PLIUS is potentially effective as a disease and symptom modifying intervention in patients with early knee OA.
Read the detailed description
Osteoarthritis (OA), the most common form of arthritis, is a prevalent and debilitating disease without therapies that alter disease progress and is currently managed with symptom-modifying therapies that are only modestly effective. In spite of substantial progress in understanding the pathogenesis of OA, no effective disease modifying interventions have been established. Degenerative joint cartilage is a central feature of OA, yet joint cartilage has a limited capacity for repair. Results from animal research demonstrate that pulsed low intensity ultrasound (PLIUS) mechanically stimulates, and may promote, cartilage repair. This exploratory trial will investigate whether PLIUS is potentially effective as a disease and symptom modifying intervention in patients with early knee OA.
- Conditions
- Osteoarthritis, Degenerative
- Being tested
- Pulsed Low Intensity Ultrasound, Sham Comparator
- Keywords
- Knee Osteoarthritis, Pulsed Low Intensity Ultrasound
- Medical subject headings
- Joint Diseases, Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pulsed Low Intensity UltrasoundDevice
20 minutes daily for 48 weeks
Sham ComparatorDevice
20 minutes daily for 48 weeks
| Study group | Role | What they receive |
|---|---|---|
| Sham | Sham comparator | Treatment to index knee with sham device for 48 weeks Receives: Device: Sham Comparator |
| PLIUS | Experimental | Treatment to index knee with PLIUS device for 48 weeks Receives: Device: Pulsed Low Intensity Ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Co-Primary Measure: a) Symptom Reduction: OMERACT-OARSI Treatment Responsiveness
Outcome Measures in Rheumatology Clinical Trials- Osteoarthritis Research Society International (OMERACT-OARSI) Response incorporates changes in pain and global assessment to define response in OA clinical trials. A response is classified as: 1) An improvement in either pain or function of at least 50 percent accompanied by an absolute decrease of at least 20 mm on the visual-analogue scale for pain or function, OR 2) The occurrence of at least two of the following: a) a decrease in pain of at least 20 percent accompanied by a decrease of at least 10 mm on the visual-analogue scale; b) an improvement in function of at least 20 percent and a decrease of at least 10 mm on the visual-analogue scale; c) an increase in the patient's global assessment score by at least 20 percent accompanied by a decrease of at least 10 mm on the visual-analogue scale
Measured: 48 weeks
Co-Primary Measure: b) Disease Modification as Measured by Change From Baseline in Cartilage Thickness of the Central Medial Femoral Condyle Disease
The study has been designed to determine if PLIUS potentially diminishes articular cartilage thinning by measuring cartilage thickness in the tibial femoral joint. The measure selected to best evaluate this is cartilage thickness of the central medial femoral condyle because studies of the OAI (Osteoarthritis Initiative) data have shown this region to be among those most sensitive to change and, due to the anatomical positioning of the device, the most likely to be affected by treatment.
Measured: Baseline, 48 weeks
Secondary outcomes (10)
Change From Baseline in WOMAC Stiffness Subscale Score
The WOMAC® Index questionnaire is a tri-dimensional, disease-specific, self-administered, health status measure. It probes clinically important, patient-relevant symptoms in the areas of pain, stiffness and physical function in patients with osteoarthritis of the hip and/or knee. The WOMAC has been linguistically validated and is a reliable and responsive measure of outcome, and has been used in diverse clinical and interventional environments. Range is from 0 - 200. The higher the score, the worse the symptoms.
Measured: Baseline, week 24, week 48
Change From Baseline in WOMAC Pain Subscale Score
The WOMAC® Index questionnaire [33] is a tri-dimensional, disease-specific, self-administered, health status measure. It probes clinically important, patient-relevant symptoms in the areas of pain, stiffness and physical function in patients with osteoarthritis of the hip and/or knee. The WOMAC has been linguistically validated and is a reliable and responsive measure of outcome, and has been used in diverse clinical and interventional environments. WOMAC pain scores from 0-500 mm. The higher the score, the worse the symptoms.
Measured: Baseline, week 24, week 48
Change From Baseline in WOMAC Functional Limits Subscale Score
The WOMAC® Index questionnaire [33] is a tri-dimensional, disease-specific, self-administered, health status measure. It probes clinically important, patient-relevant symptoms in the areas of pain, stiffness and physical function in patients with osteoarthritis of the hip and/or knee. The WOMAC has been linguistically validated and is a reliable and responsive measure of outcome, and has been used in diverse clinical and interventional environments. Range is from 0 - 1700. The higher the score, the worse the symptoms.
Measured: Baseline, week 24, week 48
Change From Baseline in Total WOMAC Score
The WOMAC® Index questionnaire is a tri-dimensional, disease-specific, self-administered, health status measure. It probes clinically important, patient-relevant symptoms in the areas of pain, stiffness and physical function in patients with osteoarthritis of the hip and/or knee. The WOMAC has been linguistically validated and is a reliable and responsive measure of outcome, and has been used in diverse clinical and interventional environments. Range is from 0 - 2400. The higher the score, the worse the symptoms.
Measured: Baseline, week 24, week 48
Change From Baseline in Patient Global Assessment of Disease Status
A patient global assessment of disease status on a Visual Analog Scale (VAS) will be measured at each clinic visit. Patients will be asked to quantify their disease status on a 100 mm VAS as follows: "Considering all the ways your arthritis of the knee affects you, mark 'X' on the scale for how well you are doing." The scale shows the left hand marker "Very Well", and the right hand marker "Very Poor." Range 0 to 100 mm. The higher the score, the worse the symptoms.
Measured: Baseline, week 24, week 48
Change From Baseline in Investigator Global Assessment of Disease Status
An investigator global assessment of disease status on a 100 mm VAS was measured at each clinic visit as follows: "Make a global assessment of the patient's disease status, with regard to the index knee, by marking an 'X' on the scale below.", with left hand marker "Very Well" and right hand marker "Very Poor." Range 0 to 100 mm. The higher the score, the worse the symptoms.
Measured: Baseline, week 24, week 48
Change From Baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) Constant Pain Subscale
This 11-item tool is designed to assess pain in individuals with knee osteoarthritis taking into account both constant and intermittent pain experiences. This tool is designed to be interviewer-administered. Study participants are asked to respond to the questionnaire items based on index knee in the past week (i.e., past 7-day period). Study participants responded to all questions for the same joint. This tool is intended to be responsive to change in OA pain over time or with treatment. Range 0 to 100 mm. The higher the score, the worse the symptoms.
Measured: Baseline, week 24, week 48
Change From Baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) Intermittent Pain Subscale
This 11-item tool is designed to assess pain in individuals with knee osteoarthritis taking into account both constant and intermittent pain experiences. This tool is designed to be interviewer-administered and takes less than 10 minutes to complete. Study participants will be asked to respond to the questionnaire items based on index knee in the past week (i.e., past 7-day period). Study participants will respond to all questions for the same joint. This tool is intended to be responsive to change in OA pain over time or with treatment. Range 0 to 100 mm. The higher the score, the worse the symptoms.
Measured: Baseline, week 24, week 48
Change From Baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) Total Pain Score
This 11-item tool is designed to assess pain in individuals with knee osteoarthritis taking into account both constant and intermittent pain experiences. This tool is designed to be interviewer-administered and takes less than 10 minutes to complete. Study participants will be asked to respond to the questionnaire items based on index knee in the past week (i.e., past 7-day period). Study participants will respond to all questions for the same joint. This tool is intended to be responsive to change in OA pain over time or with treatment. Range 0 to 100 mm. The higher the score, the worse the symptoms.
Measured: Baseline, week 24, week 48
Number of Participants Discontinuing the Study Device Due to an Adverse Device Event
Difference between study groups in number of participants who discontinued usage of the study device due to adverse device events at 4, 8, 12, 24, 36, and 48-week visits.
Measured: Baseline, 4, 8, 12, 24, 36, and 48-week visits
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2014 (estimated)
- Study start22 May 2015
- Primary completion1 Jun 2020
- Study completion30 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Osteoarthritis, DegenerativeStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants in this double-blind, randomized, sham-controlled trial will be randomly assigned to receive either sham or PLIUS device for 48 weeks.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Daniel O Clegg, MD, Principal investigator, VA Salt Lake City Health Care System, Salt Lake City, UT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02034409
- Sponsor's protocol ID
- CLIN-006-13S
- Other IDs
- CXI01CX000954-01A1
- Acronym
- PLUS+OA
- Status last verified
- Oct 2021
- First submitted
- 9 Jan 2014
- Last updated
- 18 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Sawitzke AD, Jackson CG, Carlson K, Bizien MD, Leiner M, Reda DJ, Sindowski T, Hanrahan C, Spencer RG, Kwoh CK, Lee SJ, Hose K, Robin L, Cain DW, Taylor MD, Bangerter N, Finco M, Clegg DO. Effect of Pulsed Low-Intensity Ultrasonography on Symptom Relief and Tibiofemoral Articular Cartilage Thickness Among Veterans Affairs Enrollees With Knee Osteoarthritis: A Randomized Clinical Trial. JAMA Netw Open. 2022 Mar 1;5(3):e220632. doi: 10.1001/jamanetworkopen.2022.0632.
PubMed 35258579
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial to Assess Low-Intensity Ultrasound in Osteoarthritis
- ClinicalTrials.gov ID
- NCT02034409
- Acronym / sponsor ID
- PLUS+OA / CLIN-006-13S
- Conditions
- Osteoarthritis, Degenerative
- Keywords
- Knee Osteoarthritis, Pulsed Low Intensity Ultrasound
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 22 May 2015 (actual)
- Primary completion
- 1 Jun 2020 (actual)
- Study completion
- 30 Sep 2020 (actual)
- First posted
- 13 Jan 2014 (estimated)
- Results
- Posted 18 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this exploratory trial is to investigate whether PLIUS is potentially effective as a disease and symptom modifying intervention in patients with early knee OA.
Detailed description
Osteoarthritis (OA), the most common form of arthritis, is a prevalent and debilitating disease without therapies that alter disease progress and is currently managed with symptom-modifying therapies that are only modestly effective. In spite of substantial progress in understanding the pathogenesis of OA, no effective disease modifying interventions have been established. Degenerative joint cartilage is a central feature of OA, yet joint cartilage has a limited capacity for repair. Results from animal research demonstrate that pulsed low intensity ultrasound (PLIUS) mechanically stimulates, and may promote, cartilage repair. This exploratory trial will investigate whether PLIUS is potentially effective as a disease and symptom modifying intervention in patients with early knee OA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants in this double-blind, randomized, sham-controlled trial will be randomly assigned to receive either sham or PLIUS device for 48 weeks.
| Arm | Type | Receives |
|---|---|---|
| Sham | Sham comparator | Device: Sham ComparatorTreatment to index knee with sham device for 48 weeks |
| PLIUS | Experimental | Device: Pulsed Low Intensity UltrasoundTreatment to index knee with PLIUS device for 48 weeks |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 40 years of age or older, and a US Military Veteran
- Clinical symptoms of osteoarthritis for at least 6 months
- Pain in the index knee on motion or weight bearing for the majority of days during the month before screening
- Clinical diagnosis of primary osteoarthritis of the knee based on clinical and radiographic criteria
- American Rheumatism Association Functional Class I, II, or III
Key exclusion criteria (14 listed)
- Concurrent medical/arthritis condition(s), or any other illness per the opinion of the investigator, that could interfere with the evaluation of pain or efficacy
- Spine or hip pain of significant magnitude
- History of significant ligament or meniscal injury of the index joint requiring surgical repair
- Arthroscopy of the index knee within 6 months of study entry
- Unable to undergo MRI of the knee
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pulsed Low Intensity Ultrasound20 minutes daily for 48 weeks | Device | PLIUS |
| Sham Comparator20 minutes daily for 48 weeks | Device | Sham |
Primary outcome
Co-Primary Measure: a) Symptom Reduction: OMERACT-OARSI Treatment Responsiveness
Time frame: 48 weeks
Outcome Measures in Rheumatology Clinical Trials- Osteoarthritis Research Society International (OMERACT-OARSI) Response incorporates changes in pain and global assessment to define response in OA clinical trials. A response is classified as: 1) An improvement in either pain or function of at least 50 percent accompanied by an absolute decrease of at least 20 mm on the visual-analogue scale for pain or function, OR 2) The occurrence of at least two of the following: a) a decrease in pain of at least 20 percent accompanied by a decrease of at least 10 mm on the visual-analogue scale; b) an improvement in function of at least 20 percent and a decrease of at least 10 mm on the visual-analogue scale; c) an increase in the patient's global assessment score by at least 20 percent accompanied by a decrease of at least 10 mm on the visual-analogue scale
Co-Primary Measure: b) Disease Modification as Measured by Change From Baseline in Cartilage Thickness of the Central Medial Femoral Condyle Disease
Time frame: Baseline, 48 weeks
The study has been designed to determine if PLIUS potentially diminishes articular cartilage thinning by measuring cartilage thickness in the tibial femoral joint. The measure selected to best evaluate this is cartilage thickness of the central medial femoral condyle because studies of the OAI (Osteoarthritis Initiative) data have shown this region to be among those most sensitive to change and, due to the anatomical positioning of the device, the most likely to be affected by treatment.
10 secondary outcomes
Change From Baseline in WOMAC Stiffness Subscale Score
Time frame: Baseline, week 24, week 48
Change From Baseline in WOMAC Pain Subscale Score
Time frame: Baseline, week 24, week 48
Change From Baseline in WOMAC Functional Limits Subscale Score
Time frame: Baseline, week 24, week 48
Change From Baseline in Total WOMAC Score
Time frame: Baseline, week 24, week 48
Change From Baseline in Patient Global Assessment of Disease Status
Time frame: Baseline, week 24, week 48
Change From Baseline in Investigator Global Assessment of Disease Status
Time frame: Baseline, week 24, week 48
Change From Baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) Constant Pain Subscale
Time frame: Baseline, week 24, week 48
Change From Baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) Intermittent Pain Subscale
Time frame: Baseline, week 24, week 48
Change From Baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) Total Pain Score
Time frame: Baseline, week 24, week 48
Number of Participants Discontinuing the Study Device Due to an Adverse Device Event
Time frame: Baseline, 4, 8, 12, 24, 36, and 48-week visits
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35258579Sawitzke AD, Jackson CG, Carlson K, Bizien MD, Leiner M, Reda DJ, Sindowski T, Hanrahan C, Spencer RG, Kwoh CK, Lee SJ, Hose K, Robin L, Cain DW, Taylor MD, Bangerter N, Finco M, Clegg DO. Effect of Pulsed Low-Intensity Ultrasonography on Symptom Relief and Tibiofemoral Articular Cartilage Thickness Among Veterans Affairs Enrollees With Knee Osteoarthritis: A Randomized Clinical Trial. JAMA Netw Open. 2022 Mar 1;5(3):e220632. doi: 10.1001/jamanetworkopen.2022.0632.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel O Clegg, MD principal investigator
VA Salt Lake City Health Care System, Salt Lake City, UT
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pulsed Low Intensity Ultrasound in people with Osteoarthritis, Degenerative, run by VA Office of Research and Development at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Co-Primary Measure: a) Symptom Reduction: OMERACT-OARSI Treatment Responsiveness (time frame: 48 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02034409, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2021.