Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 96 of 33575 for:    Placebo AND placebo effect

Saline Injections vs Education and Exercise in Knee Osteoarthritis (DISCO)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03843931
Recruitment Status : Not yet recruiting
First Posted : February 18, 2019
Last Update Posted : June 28, 2019
Sponsor:
Information provided by (Responsible Party):
Marius Henriksen, Frederiksberg University Hospital

Brief Summary:

Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition mainly affecting older people, causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended by leading international organisations and authorities based on extensive research that documents that exercise and education are superior to no-attention control groups.

In Denmark, an initiative to implement these recommendations was initiated in 2013. The initiative is called Good Life with osteoArthritis in Denmark (GLA:D) and aims at facilitating high quality care of patients with OA in the Danish population. The core components of the GLA:D program are 8 weeks of education (2 sessions) and supervised neuromuscular exercise delivered by GLA:D certified physiotherapists. The GLA:D concept has been exported to Canada, China and Australia.

While several randomised controlled trials have investigated exercise and education for knee OA none have used a placebo comparison group. The effect size of exercise plus education therapy is in line with the current theories that the contact with a caring clinician that believes in efficacy of the treatments he/she provides can result in beneficial health effects. In exercise and education programs (such as the GLA:D program) frequent and lengthy contacts with a physiotherapist are typically necessary. Hence, a significant proportion of the beneficial effects can be expected to be attributable to placebo or placebo.like effects.

In trials of intra-articular treatment of knee OA (e.g. in trials of corticosteroids, viscosupplementation, or platelet-rich-plasma) saline injections are a commonly used as placebo comparator. While saline is recognised as a pharmacologically inert agent, a recent systematic review and meta-analysis concluded that although intra-articular saline injection is often used as a "placebo" treatment in clinical trials for knee OA it can provide substantial pain relief. The effect size of saline injections is in line with the current theories that the "invasiveness" of a procedure is an important determinant for the magnitude of placebo effects.

This trial aims to compare a widely used 8-week education plus exercise program (the GLA:D program) with 4 intra-articular saline injections as treatments of knee OA symptoms. Outcomes are taken at baseline, after 8-weeks of treatment (week 9) and after additionally 4 weeks of follow-up (week 12).


Condition or disease Intervention/treatment Phase
Osteoarthritis, Knee Behavioral: GLA:D Drug: Intra-articular saline injection Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open Label, Parallel Group Study in Patients With Knee Osteoarthritis to Compare Intra-articular Saline Injections With Education Plus Exercise Therapy
Estimated Study Start Date : August 1, 2019
Estimated Primary Completion Date : November 1, 2020
Estimated Study Completion Date : December 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: GLA:D
8 weeks of education (1 session/week for 2 weeks) and exercise therapy (2 sessions/week for 6 week)
Behavioral: GLA:D
The GLA:D exercise and education program is an 8-week treatment program delivered by GLA:D certified physiotherapists. It consists of 2 educational sessions over 2 weeks (1/week in week 1 and 2) and 12 exercise sessions over 6 weeks (2/week in weeks 2 thru 8) The 2 educational sessions provide knowledge of OA, treatment and self-management, with a special focus on exercise and its benefits. The exercise part lasts for 6 weeks with 2 exercise sessions per week of approximately 1 hour (12 sessions total). The exercise sessions are group based at a facility supervised by a GLA:D certified physiotherapist. The goal is the obtain muscle control and stability in situations resembling daily life and/or more strenuous activities.
Other Name: Education and Exercise

Placebo Comparator: Intra-articular saline injection
Intra-articular saline injection (5 ml of 0.9% sodium chloride) every 2 weeks over an 8-week period
Drug: Intra-articular saline injection

Four [4] dosages of 5 ml intra-articular isotonic saline (0.9% (9 mg/mL) Sodium Chloride Injection (sterile, isotonic solution of sodium chloride and sterile water for injection)) every other week from baseline (week 1, 3, 5 and 7 = 4 injections).

The injections will be carried out with a 21 gauge (38 mm) needle and a Luer-lock syringe under ultrasound guidance to ensure that the needle is inserted into the study knee joint cavity and document correct deposition of the bolus in the joint cavity.

If the investigator detects presence of excessive joint fluid during the ultrasound guided preparation of the injection, this will be aspirated before injection of the saline - if possible.

Other Name: Physiological salinated water




Primary Outcome Measures :
  1. Change from baseline in knee pain [ Time Frame: week 9 ]

    Assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale (patient-reported questionnaire).

    The KOOS pain subscale consists of 9 questions with a five-point Likert scale scoring system (ranging from 0 (least severe) to 4 (most severe)). The answers are summed and a 0-100 normalized score is calculated with 0 indicating extreme pain and 100 indicating no pain.



Secondary Outcome Measures :
  1. Change from baseline in physical function [ Time Frame: week 9 and week 12 ]
    Assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS) physical function subscale (patient-reported questionnaire)The KOOS physical function subscale consists of 17 questions with a five-point Likert scale scoring system (ranging from 0 (least severe) to 4 (most severe)). The answers are summed and a 0-100 normalized score is calculated with 0 indicating extreme functional impairment and 100 indicating no functional impairment.

  2. Change from baseline in symptoms [ Time Frame: week 9 and week 12 ]
    Assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS) symptoms subscale (patient-reported questionnaire) The KOOS symptoms subscale consists of 7 questions with a five-point Likert scale scoring system (ranging from 0 (least severe) to 4 (most severe)). The answers are summed and a 0-100 normalized score is calculated with 0 indicating extreme symptoms and 100 indicating no symptoms.

  3. Change from baseline in knee related quality of life [ Time Frame: week 9 and week 12 ]
    Assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS) knee related quality of life subscale (patient-reported questionnaire) The KOOS knee related quality of life subscale consists of 4 questions with a five-point Likert scale scoring system (ranging from 0 (least severe) to 4 (most severe)). The answers are summed and a 0-100 normalized score is calculated with 0 indicating extremely poor knee related quality of life pain and 100 indicating very good knee related quality of life .

  4. Change from baseline in patient's global assessment of impact of osteoarthritis [ Time Frame: week 9 and week 12 ]
    Assessed by a 0-100 mm visual analog scale (VAS)(patient-reported questionnaire)

  5. Number of treatment responders according to OMERACT-OARSI response criteria [ Time Frame: week 9 and week 12 ]

    following two conditions is observed at the post-baseline assessment:

    • In either pain (KOOS pain subscale) or function (KOOS function subscale), a high improvement in the subscale, where high improvement in a subscale is achieved if there is both a > 50% improvement from Baseline and an absolute change from Baseline of > 20 points (0-100 scale), OR
    • Improvement in at least two of the following three:

      1. Improvement in pain (KOOS pain subscale) defined as > 20% improvement from Baseline and an absolute change from Baseline of > 10 points (0-100 scale)
      2. Improvement in function (KOOS function subscale) defined as > 20% improvement from Baseline and an absolute change from Baseline of > 10 points (0-100 scale)
      3. Improvement in patient's global assessment defined as > 20% improvement from Baseline and an absolute change from Baseline of > 10 mm (0-100 scale)

  6. Change from baseline in 4x10 meter fast walk test [ Time Frame: Week 9 and week 12 ]

    The 4x10 meter fast walk test (40mFWT) is a physical performance test that quantifies short distance walking performance. The 40mFWT is a measure of walking speed over short distances and changing direction during walking. It is recommended as a performance-based test to assess physical function in people diagnosed with hip or knee OA.

    The participant is asked to walk as quickly but as safely as possible to a mark 10 m away, return, and repeat for a total distance of 40 m. Regular walking aid is allowed and recorded. Time of one trial, with turn time excluded, is recorded and expressed as speed m/s by dividing distance (40 m) by time (s).


  7. Change from baseline in the 30 seconds chair stand test [ Time Frame: Week 9 and week 12 ]

    The 30 seconds chair stand test (30sCST) is a physical performance test that quantifies how many sit-to-stand movements an individual is able to perform within 30 seconds. The 30sCST is a measure of balance during functional activities and lower extremity function and strength. It is recommended as a performance-based test to assess physical function in people diagnosed with hip or knee OA.

    From the sitting position in the middle of seat with feet shoulder width apart, flat on the floor, arms crossed at chest, the participant is asked to stand completely up, then sit completely back down, repeatedly for 30 seconds. The total number of complete chair stands (up and down represents one stand) is counted. There is given only one trial. If a full stand is completed at 30 seconds, then this is counted in the total. The same chair is used at all assessments.


  8. Change from baseline in Stair climbing test [ Time Frame: Week 9 and week 12 ]

    A stair climbing test (SCT) is a physical performance test that quantifies how fast an individual is able to ascend and descend a flight of stairs in a usual manner. The SCT is a measure of balance during functional activities and lower extremity function and strength. It is recommended as a performance-based test to assess physical function in people diagnosed with hip or knee OA.

    The participant is asked to ascend and descend a flight of stairs in a usual manner, and at a safe and comfortable pace. Use of any walking aid and handrail is permitted and recorded. Total time to ascend and descend steps for one trial is recorded in seconds. The same flight of stairs is used at all assessments.



Other Outcome Measures:
  1. Joint fluid aspiration volume [ Time Frame: week 9 and 12 ]
    During an ultrasound examination, presence of excess joint fluid will be visualised and, if possible, aspirated by inserting a needle into the joint cavity (under ultrasound guidance). The volume (in ml) of the aspirated fluid will recorded. The ultrasound examination and fluid removal will be conducted by a trained medical doctor (rheumatologist or orthopaedic surgeon).

  2. Change from baseline in swollen knee joint count [ Time Frame: week 9 and 12 ]
    An investigator (medical doctor) will examine both knees and record if they are swollen or not based on the presence of palpable effusion. The outcome of the examination will be recorded for each knee as a dichotomous score (present/absent).

  3. Change in current knee pain at treatment visits [ Time Frame: Week 1, 2, 3, 4, 5, 6, 7, and 8 ]

    At arrival to each treatment session (education, exercise or injection) we will ask the participants to assess their current knee pain in the target knee a 0-10 points numerical rating scale, with 0 representing "no pain" and 10 representing "worst imaginable pain".

    The assessment is repeated when the participants leave the session and the change on that day is calculated.


  4. Time course pattern of changes from baseline in knee OA symptoms during the treatment period [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7, and 8 ]
    Assessed by repeated administration of the Knee injury and Osteoarthritis Outcome Score (KOOS)(patient-reported questionnaire) The KOOS consists of 42 items covering five domains, namely, Pain (9 items), Symptoms (7 items), Activities of Daily Living (ADL) (17 items), Sports and Recreation (5 items), and knee-related QoL (4 items). The KOOS adopts a five-point Likert scale scoring system (ranging from 0 (least severe) to 4 (most severe)). A normalized score is calculated for each domain with 0 indicating extreme symptoms and functional impairment and 100 indicating no symptoms and functional impairment.

  5. Time course pattern of changes from baseline in morning knee OA pain [ Time Frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9 and 12 ]
    Assessed by repeated administration of a 100 mm analogue scale (VAS) relating to the degree of the patient's perceived averaged morning knee pain during the last week with anchors: 0="No pain" and 100 = "Worst imaginable pain". (patient-reported questionnaire)

  6. Change from baseline in intermittent and constant knee pain [ Time Frame: Week 9 and 12 ]
    Assessed by the Measure of Intermittent and Constant Osteoarthritis Pain - ICOAP (patient-reported questionnaire).

  7. Use of acetaminophen and ibuprofen during study participation [ Time Frame: Baseline, Week 9 and 12 ]
    Patient reported use of acetaminophen



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥50 years.
  2. Body Mass index ≤ 35
  3. A clinical diagnosis of tibiofemoral OA in the target knee according to the American College of Rheumatology (12).
  4. Average knee pain in the last week during weight bearing activities of at least 4 on a 0 to 10 points scale (0=no pain; 10=worst possible pain).
  5. Verification of clinical diagnosis by definite tibiofemoral OA on posterior-anterior weight bearing semi-flexed knee radiographs with severity equivalent to Kellgren and Lawrence grade 2 or more.

Exclusion Criteria:

  1. Intra-articular treatments of any kind of either knee 3 months before inclusion
  2. Scheduled surgery during study participation
  3. Knee joint fluid aspiration within 3 month of baseline visit
  4. Participation in exercise therapy within 3 months of baseline visit
  5. Evidence of other inflammatory joint disease (e.g. rheumatoid arthritis or gout)
  6. History of knee surgery within 12 months
  7. History of arthroplasty in the target knee
  8. Use of oral glucocorticoids
  9. Use of synthetic or non-synthetic opioids
  10. Other musculoskeletal, neurological, medical conditions precluding participation in exercise
  11. Contraindications to intra-articular injections, such as wounds or skin rash over injection site.
  12. Contraindications to exercise
  13. Planning to start other treatment for knee OA in the study participation period
  14. Regional pain syndromes
  15. Generalised pain syndromes such as fibromyalgia
  16. Lumbar or cervical nerve root compression syndromes
  17. Any other condition or impairment that, in the opinion of the investigator, makes a potential participant unsuitable for participation or which obstruct participation, such as large knee joint effusion, uncontrolled diabetes, psychiatric disorders, or opiate dependency.

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): NCT03843931


Contacts
Layout table for location contacts
Contact: Elisabeth Bandak, PhD +4538164155 elisabeth.ann.bandak@regionh.dk
Contact: Line Rustad +4538164158

Locations
Layout table for location information
Denmark
The Parker Institute, Frederiksberg Hospital
Copenhagen, Denmark, 2000
Sponsors and Collaborators
Marius Henriksen
Investigators
Layout table for investigator information
Study Director: Marius Henriksen, PhD The Parker institute
Principal Investigator: Henning Bliddal, DMSc The Parker institute

Layout table for additonal information
Responsible Party: Marius Henriksen, Professor, Frederiksberg University Hospital
ClinicalTrials.gov Identifier: NCT03843931     History of Changes
Other Study ID Numbers: APPI2-PT-2019-01
First Posted: February 18, 2019    Key Record Dates
Last Update Posted: June 28, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: We will share the IPD, protocol and SAP, but the circumstances and timing has not been decided yet

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Marius Henriksen, Frederiksberg University Hospital:
Exercise
Placebo
Injection

Additional relevant MeSH terms:
Layout table for MeSH terms
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases