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A Pilot Trial to Assess Low-Intensity Ultrasound in Osteoarthritis (PLUS+OA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02034409
Recruitment Status : Completed
First Posted : January 13, 2014
Results First Posted : October 18, 2021
Last Update Posted : October 18, 2021
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief 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.

Condition or disease Intervention/treatment Phase
Osteoarthritis, Degenerative Device: Pulsed Low Intensity Ultrasound Device: Sham Comparator Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Pilot Trial to Assess Low-Intensity Ultrasound in Osteoarthritis
Actual Study Start Date : May 22, 2015
Actual Primary Completion Date : June 1, 2020
Actual Study Completion Date : September 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Sham Comparator: Sham
Treatment to index knee with sham device for 48 weeks
Device: Sham Comparator
20 minutes daily for 48 weeks

Experimental: PLIUS
Treatment to index knee with PLIUS device for 48 weeks
Device: Pulsed Low Intensity Ultrasound
20 minutes daily for 48 weeks




Primary Outcome Measures :
  1. 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

  2. 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.


Secondary Outcome Measures :
  1. Change From Baseline in WOMAC Stiffness Subscale Score [ Time Frame: Baseline, week 24, week 48 ]
    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.

  2. Change From Baseline in WOMAC Pain Subscale Score [ Time Frame: Baseline, week 24, week 48 ]
    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.

  3. Change From Baseline in WOMAC Functional Limits Subscale Score [ Time Frame: Baseline, week 24, week 48 ]
    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.

  4. Change From Baseline in Total WOMAC Score [ Time Frame: Baseline, week 24, week 48 ]
    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.

  5. Change From Baseline in Patient Global Assessment of Disease Status [ Time Frame: Baseline, week 24, week 48 ]
    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.

  6. Change From Baseline in Investigator Global Assessment of Disease Status [ Time Frame: Baseline, week 24, week 48 ]
    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.

  7. Change From Baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) Constant Pain Subscale [ Time Frame: Baseline, week 24, week 48 ]
    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.

  8. Change From Baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) Intermittent Pain Subscale [ Time Frame: Baseline, week 24, week 48 ]
    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.

  9. Change From Baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) Total Pain Score [ Time Frame: Baseline, week 24, week 48 ]
    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.

  10. 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 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02034409


Locations
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United States, California
VA San Diego Healthcare System, San Diego, CA
San Diego, California, United States, 92161
United States, Texas
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
Dallas, Texas, United States, 75216
United States, Utah
VA Salt Lake City Health Care System, Salt Lake City, UT
Salt Lake City, Utah, United States, 84148
Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Principal Investigator: Daniel O Clegg, MD VA Salt Lake City Health Care System, Salt Lake City, UT
  Study Documents (Full-Text)

Documents provided by VA Office of Research and Development:
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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT02034409    
Other Study ID Numbers: CLIN-006-13S
CXI01CX000954-01A1 ( Other Identifier: eRA project Reference )
First Posted: January 13, 2014    Key Record Dates
Results First Posted: October 18, 2021
Last Update Posted: October 18, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by VA Office of Research and Development:
Knee Osteoarthritis
Pulsed Low Intensity Ultrasound
Additional relevant MeSH terms:
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Osteoarthritis
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases