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Trial registered on ANZCTR


Registration number
ACTRN12615000227594
Ethics application status
Approved
Date submitted
6/01/2015
Date registered
12/03/2015
Date last updated
30/10/2018
Date data sharing statement initially provided
30/10/2018
Date results information initially provided
30/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Stepped Care Approach for Medial Tibiofemoral Osteoarthritis (STrEAMline)
Scientific title
STrEAMline: The remission of symptoms in Tibiofemoral Osteoarthritis following an adaptive treatment strategy in overweight/obese participants
Secondary ID [1] 285917 0
NIL
Universal Trial Number (UTN)
U1111-1165-7198
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medial tibiofemoral Osteoarthritis 293835 0
Obesity 294229 0
Depression 294230 0
Condition category
Condition code
Musculoskeletal 294136 294136 0 0
Osteoarthritis
Mental Health 294137 294137 0 0
Depression
Diet and Nutrition 294548 294548 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1 – 18 week diet and exercise as prescribed by the Healthy Weight for Life program (healthyweightforlife.com.au)
The Healthy Weight for Life is a specialised arthritis chronic disease management program that targets multiple modifiable OA risk factors by carefully integrating:
a. Weight loss and improved nutrition - a stepped intervention designed to achieve a progressive and practical implementation of normal, healthy portion-controlled eating and drinking, through education and resources. The participants will receive a resource pack that contains the Portion Planning eating system and tools (Healthy Weight for Life week-by-week guide book, KickStart (trademark) meal replacement, portion planner disc, reusable drink bottle, insulated combined lunch and snack bag and a tape measure for taking waist measurements) and the relevant instructions on how to use it. Throughout the program, the participants will be given a choice of meal replacement flavours and provided access to recipes for low fat and low glycaemic index meals. During the first 6 weeks (Motivational Loss Phase) 2 meals each day are replaced with a VLCD meal replacement KicStart (trademark). As patients move through the remaining 2 phases of the Integrated Osteoarthritis Management program, the number of meals replaced with KicStart (trademark) is gradually reduced to zero as they progressively build up the new sustainable healthy eating and lifestyle habits that are needed to keep weight under control in the longer term. Adequate hydration will also be encouraged using “free drinks” (e.g. mineral water, vegetable juice). Online healthy eating and lifestyle education will be provided, as will coaching and personalised telephone motivation, support and advice.
b. Muscle strengthening - an exercise program focused on balance, strengthening and improving range of motion of quadriceps, calf, hamstrings, gluteal and hip flexor and abductor muscles. This is a home-based intervention for which the participants will receive resources developed in collaboration with physiotherapists. The resources and tools included are a manual with step-by-step instructions for 42 different exercises across 3 levels, a DVD demonstrating and explaining each of the 42 exercises, resistance exercise tube and a hot and cold pack for pain management. Participants will be encouraged to maintain a routine of 3 sets of 10 minutes of physical daily activity (such as walking or water based), and between 12 to 15 level 1 strength, balance and mobility exercises that should be performed at least 3 times per week, on phase 1 (weeks 1-6) of the program, ideally separating each session by a day or two. Once comfortably completing the level 1 exercises, there to move Phase 2 (weeks 7-12), which will require a 1 x 30 minutes (or more) of daily physical activity (either land or water based), and between 12 to 15 level 2 strength, balance and mobility exercises that should be performed at least 3 times per week, ideally separating each session by a day or two. Finally, phase 3 (weeks 13 - ongoing) will require 30 minutes (or more) of physical activity daily (either land or water based) or the use of a pedometer to target 10,000 steps per day and between 12 to 15 level 3 strength, balance and mobility exercises that should be performed at least 3 times per week, ideally separating each session by a day or two. The time taken to perform the strength, balance and mobility exercises is not prescribed. Participants are asked to only exercise within their physical capabilities and to not continue exercising with increasing pain or pain that is moderate to severe. No specific target intensity is prescribed as the range of capabilities varies widely. If there are particular exercises in a level that they cannot do for any reason, they are to continue with the exercises that can be comfortably managed.
c. Monitoring and Engagement - A central team of clinical, navigation and logistical staff provide personalised engagement to each individual. PrimaLinx (Trademark) software enables extensive "real time" monitoring and analysis of each individual's symptom, biometric, satisfaction and engagement data. A live dashboard then directs proactive engagement by the central team through a multi-channel 2-way person communication (phone, SMS, email, electronic message board and reply paid post). All participants complete a weekly online weight and waist circumference tracking record that is monitored for progress towards set targets and engagement. Participants also have the option to complete a Diet and Activity Journal to identify where portions or habits can be improved.

- Reassessment at 20 weeks – If participants have achieved a PASS score that is equivalent to disease remission they will continue on the diet and exercise protocol until the 32 week mark.
- Participants that have not achieved remission will enter the Adaptive Treatment Stage


Arm 2 – Adaptive Treatment Stage
- At this stage, participants will be evaluated for referral into one of the three treatment arms depending on which of the following impediments present as the most significant:

- Depression: For patients that score less than or equal to 14 on the DASS-21, defined as moderately depressed.
Referred to CRUFAD – an online Cognitive Behavioural Therapy (CBT) course for the treatment of depression. This course involves 6 online lessons to be completed over 12-week period. The approximate duration is 30 minutes per session. This course provides a structured learning plan, downloadable materials, and guidance from a dedicated Clinical Psychologist at St Vincent’s Hospital who is experienced in the treatment of depression and anxiety. Research shows that online CBT programs can be just as effective as face-to-face CBT, whilst being quicker to access and more convenient than face-to-face treatments.
COURSE CONTENT:
- Lesson 1 - The diagnosis: Learning about the symptoms of depression
- Lesson 2 - Monitoring Your Thoughts and Activities: Identify the things a person does and the things a person thinks that maintain their symptoms of depression (that keeps their symptoms going)
- Lesson 3 - Learn to Improve Your Activities and Thoughts: Learn to challenge unhelpful thoughts and self-criticism.
- Lesson 4 - Facing Your Fears: Learn about how to confront your fears with step-by-step exercises.
- Lesson 5 - Being Assertive: Learn how to be assertive with effective communication techniques.
- Lesson 6 - Preventing Relapse: Learn about relapse prevention and how to stay well over the long-term.
CRUFAD research shows that three quarters of people who complete the depression course recover from symptoms of depression, and stay well over the longer term.
By the end of the program, the participant will be able to:
a. Identify their own symptoms of depression,
b. Identify the things that they do, and the thinking habits that maintain their symptoms of depression
c. Understand how depression is treated.
d. Learn and practice skills and techniques that will help them get better control over their symptoms.
e. Feel more confident in their ability to stay well over the long-term, and control heir symptoms of depression.

- Varus Thrust: Measured by clinical examiners through visual gait analysis, and if confirmed Varus Thrust, then by three-dimensional knee kinematics assessment (KneeKG System).
Participants with a varus thrust and varus malalignment of greater than or equal to 6 degrees will receive treatment to correct it via an unloader knee brace (provided free of charge to the participants).
- The Unloader FIT knee brace, developed and commercialised by Ossur, will be provided to the participants by the Australian Orthotic Technologies free of charge.
- The knee brace will be measured and fitted by a certified trained practitioner at the time of the participant's visit and inclusion to this treatment group.
- Participants will be advised to wear the brace throughout the day for normal activities of daily living. The brace will be worn for the whole duration of the Adaptive Treatment Stage (week 20 to 32).
- When first using the brace, the advice will be to gradually buildup the usage time, starting with up to 3 hours a day in active use and increase by a maximum of 1-2 hours each day.
- Participants with peripheral vascular disease, neuropathy, and sensitive skin will be monitored for any adverse reaction and will receive the appropriate required medical supervision.
- The Unloader FIT is field adaptable to relieve knee pain. Modifications to flexion/extension stops, DFS straps (Upper Dynamic Force Straps) and shell contour will only be made by certified practitioners.

- Quadriceps Weakness: Compared to normative data (maximum voluntary contraction test – dynamometer).
- Participants will follow a strengthening program designed and published by Bennell et al, 2008.
- The aim of the program is to improve the strength of the quadriceps. The participants in the quadriceps strengthening group will complete five specific non-weight-bearing exercises with the affected (most symptomatic or right) leg:
1. Quads over a roll (inner range knee extension)-using resistance of ankle weights.
2. Knee extension in sitting - start sitting with knee at 90 degrees flexion, fully extend using resistance of ankle weights.
3. Knee extension with hold at 30 degrees knee flexion - start sitting with knee at 90 degrees flexion, extend to 30 degrees using resistance of ankle weights.
4. Straight leg raise - start supine, raise leg to 30 degrees hip flexion using resistance of ankle weights.
5. Elastic band exercise - start sitting with knee at 90 degrees flexion, extend to 60 degrees against resistance of elastic band.
Ten repetitions will be performed in each set of quadriceps exercises. Two sets will be performed at the start of the program, progressing to three sets as quickly as possible. The starting weight should be the participant's 10-repetition maximum weight if possible. However, the starting weight can also be determined by asking the participant their level of effort, which should be 5-8 out of ten (hard to very hard) on the modified Borg RPE CR-10 scale for strength training. Each repetition will be performed slowly and in a controlled manner. The end position is held for five seconds initially and progressed to ten seconds. Breath holding during the isometric component of the exercises can increase blood pressure; therefore participants will be instructed to continue breathing throughout each phase (concentric, isometric and eccentric) of the exercises. Exercises should be carried out within tolerable levels of pain. The same pain monitoring scale as described above will be used and pain should subside to usual levels by the next day with no increase in swelling following the exercise session. If joint swelling or 'unacceptable' pain occurs, the resistance, frequency and/or number of repetitions will be reduced. Progression is again an important part of the program and participants will aim to increase their ankle weight or elastic band resistance at regular intervals during the program as guided by their physiotherapist. During all exercises, the level of effort experienced should be self-rated as at least five out of ten (hard) on a RPE CR-10 scale for strength training.
- Participants will be asked to perform the prescribed exercises at home four times per week, and are expected to take approximately 30-45 minutes to complete them.
- They will also be asked to have booster session visits, which will consist of 7 face to face sessions, over the 12-week period for the Adaptive Treatment Stage. These sessions will be performed on a group basis, under the supervision of a physiotherapist, and are expected to take approximately 30-45 minutes.
- There will be no formal control of adherence to the home exercise program, but the participants will be checked for form and execution, by the physiotherapist, during their booster visit sessions

- Participants with multiple problems at 20-weeks
- For those participants who fit the criteria for entry into more than one treatment arm at the 20-week assessment the following decision-making matrix will be implemented in order to categories each participant:
Depression > Varus thrust > Quadriceps weakness
- In accordance with this matrix, any participant who qualifies for multiple treatment arms – of which depression is one of them – will be treated for their depression over any problems with alignment and muscle weakness. Similarly, if a participant has both a varus thrust and quadriceps weakness they will enter the treatment arm for varus thrust.
The decision to rank these treatment modalities in this way is due to the level of impact each of these problems has to achieving remission of OA. A recent study by Shimura et al, 2014 found that pain severity in patients with depression was significantly increased in comparison to that in those without depression, suggesting that depression complicated with knee OA is associated with the symptoms rather than the severity of the disease. Furthermore, depression has a high impact on not only OA but also quality of life. For this reason, it is extremely important that all participants with depression receive adequate treatment.
Ranking varus thrust ahead of quadriceps weakness was decided with the hope that correcting existing malalignment will help to improve the mechanical functioning of the joint, and in doing so will allow the muscles that act on the knee joint to function correctly.

Final assessment at 32 weeks
- Participants in both the active treatment and control group will be reassessed at 32 weeks for their weight and BMI measurements and will have their final PASS score calculated.
Intervention code [1] 290891 0
Treatment: Other
Intervention code [2] 290892 0
Treatment: Devices
Intervention code [3] 290893 0
Behaviour
Comparator / control treatment
The Control Group will be provided with a selection of education pamphlets. These fact sheets will be taken from MyJointPain.org.au, a website which was launched in partnership with Arthritis Australia and is a source of reliable information for individuals with OA. It can inform patients if they have the disease and how to manage it. Similarly, it provides users with a collection of OA healthcare services in order to allow patients to determine who is best suited to manage their disease.
Control group
Active

Outcomes
Primary outcome [1] 293938 0
Disease Remission to be measured by the Patient Acceptable Symptom State Score (PASS)
Timepoint [1] 293938 0
At Baseline and at 20 and 32 weeks after intervention commencement
Secondary outcome [1] 312183 0
Knee pain as assessed using a Visual Analogue Scale
Timepoint [1] 312183 0
at baseline and at 20 and 32 weeks after intervention commencement
Secondary outcome [2] 312184 0
Knee Injury and Osteoarthritis Outcome Score (KOOS)
Timepoint [2] 312184 0
at baseline and at 20 and 32 weeks after intervention commencement
Secondary outcome [3] 312185 0
Comorbid diseases to be measured by Comorbidity index
Timepoint [3] 312185 0
at baseline and at 20 and 32 weeks after intervention commencement
Secondary outcome [4] 312186 0
Functional mobility to be measured by Timed up and Go test
Timepoint [4] 312186 0
at baseline and at 20 and 32 weeks after intervention commencement
Secondary outcome [5] 312189 0
Patient’s ability to walk short distances to be measured by Fast-paced walk test 40m
Timepoint [5] 312189 0
at baseline and at 20 and 32 weeks after intervention commencement
Secondary outcome [6] 312190 0
Body Mass Index (BMI)
Timepoint [6] 312190 0
at baseline and at 20 and 32 weeks after intervention commencement
Secondary outcome [7] 312191 0
Waist-Hip ratio
Timepoint [7] 312191 0
at baseline and at 20 and 32 weeks after intervention commencement
Secondary outcome [8] 312192 0
Quadriceps Strength to be measured by Hand-held dynamometer
Timepoint [8] 312192 0
at baseline and at 20 and 32 weeks after intervention commencement
Secondary outcome [9] 312193 0
Severity of depression, anxiety and stress symptoms to be measured by Depression, Anxiety and Stress Scale (DASS 21)
Timepoint [9] 312193 0
at baseline and at 20 and 32 weeks after intervention commencement
Secondary outcome [10] 312194 0
Varus thrust to be measured by Gait analysis (visual assessment and KneeKG System)
Timepoint [10] 312194 0
at baseline and at 20 and 32 weeks after intervention commencement
Secondary outcome [11] 312195 0
Knee range of motion (ROM) to be measured by Goniometry of knee extension and flexion
Timepoint [11] 312195 0
at baseline and at 20 and 32 weeks after intervention commencement
Secondary outcome [12] 312196 0
Knee alignment to be measured by Goniometry valgus and varus deformity
Timepoint [12] 312196 0
at baseline and at 20 and 32 weeks after intervention commencement
Secondary outcome [13] 312197 0
Treatment response to be measured by Qualitative question (much worse; moderately worse; slightly worse; no change; slightly better; moderately better and much better)
Timepoint [13] 312197 0
at 20 and 32 weeks after intervention commencement
Secondary outcome [14] 312198 0
Knee gait analysis to be measured by Knee KG
Timepoint [14] 312198 0
at 20 and 32 weeks after intervention commencement

Eligibility
Key inclusion criteria
- Age 50 years and over
- BMI greater than or equal to 28
- VAS pain greater than or equal to 4 out of 10
- PASS scores greater than 32.0mm for pain, 32.0mm for global assessment score and 31mm for the WOMAC questions
- Knee pain and stiffness in the past 30 days
- Radiographic evidence of a definite osteophyte
- Radiographic evidence of disease in the medial tibiofemoral compartment -Minimum grade 1 medial tibiofemoral joint space narrowing based on the Osteoarthritis Research Society International (OARSI) atlas
Minimum age
50 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Clinical evidence of predominant patellofemoral disease
- Clinical evidence of lateral tibiofemoral disease
- Any other knee pathology that is likely to be contributing to their knee pain (e.g. pes anserine bursitis, referred pain from back or hip, secondary osteoarthritis (from inflammatory rheumatic diseases such as rheumatoid arthritis or gout)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients that have been identified at baseline to have medial tibiofemoral OA will be assigned to either the intervention or the control groups using a permuted block randomisation schedule prepared by a statistician not directly involved in the conduct of the study. Allocation will be concealed in sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation schedule will be prepared by an independent statistician using random permuted blocks.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Descriptive statistics such as total number, mean (standard deviation), median (range or interquartiles) or proportions will be used to summarize the data. Data will be analysed according to intention-to-treat principles based on original group assignment. For the primary outcome, the chi-square test will used to determine whether there is a difference in disease remission rate between the two groups. Both the differences in rate and odds ratio with a 95% confident interval will be reported. A further analysis adjusting for important baseline covariates such as BMI, gender, OA KL grade etc will be conducted using a logistic regression model.
A 25% difference in disease remission rate between the two groups will make the program worthwhile. For this trial, we estimate that 45% in the control and 70% in the intervention will have disease remission at 30-week. With 68 subjects in each group there will be sufficient power (80%) to detect a significant difference (p<0.05). Considering a dropout rate of 25%, a sample size of 170 in total will be needed for the study.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 3301 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 9084 0
2065 - Royal North Shore Hospital

Funding & Sponsors
Funding source category [1] 290497 0
Government body
Name [1] 290497 0
National Health and Medical Research Council
Address [1] 290497 0
National Health and Medical Research Council
GHD Building Level 1, 16 Marcus Clarke Street, Canberra ACT 2601
Country [1] 290497 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney, Northern Clinical School
Level 7 – Clinical Administration 7C – Rheumatology Dept
Royal North Shore Hospital
Reserve Rd, St Leonards NSW 2065
Country
Australia
Secondary sponsor category [1] 289196 0
None
Name [1] 289196 0
Address [1] 289196 0
Country [1] 289196 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292154 0
Northern Sydney Coast Human Research Ethics Committee
Ethics committee address [1] 292154 0
Research Office
Kolling Building, Level 13, Pacific Hwy
Royal North Shore Hospital
St Leonards NSW 2065
Ethics committee country [1] 292154 0
Australia
Date submitted for ethics approval [1] 292154 0
07/11/2014
Approval date [1] 292154 0
08/12/2014
Ethics approval number [1] 292154 0
HREC/14/HAWKE/381

Summary
Brief summary
The current approach in the management of osteoarthritis is primarily palliative and is aimed at alleviating symptoms. By contrast, current literature is increasingly advocating the identification of prognostic indicators, such as muscle weakness, mal­alignment and depression that may be amenable to treatment. That is, to provide a more holistic approach to the management of osteoarthritis as well as to facilitate an improvement in an individual’s joint pain and function rather than treating every patient with a “one size fits all” approach.
With this is mind, the primary aim of this pilot study is to establish whether a “stepped up”, adaptive treatment protocol can increase frequency of disease remission and improve long­term functional outcomes such as pain and stiffness among persons with medial tibiofemoral knee osteoarthritis.
Participants in this pilot study will be randomized into either a control or treatment group. The treatment group will follow a diet and exercise program for 18 weeks. Reassessment of their Patient Acceptable Symptom Score (PASS) occurs at 20­week and participants who fail to reach the threshold level for disease remission based on disease symptoms and an individual’s perceived functionality will then enter into the Adaptive Treatment Protocol phase. Participants will receive additional treatment for muscle weakness, mal­alignment or depression. The control group will be provided with educational pamphlets about knee OA, largely focused on diet, exercise and weight loss.
Final follow-up and assessment of disease remission will take place at 32­week. The purpose of this protocol is to develop a clinical algorithm for individualised patient treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 53810 0
Prof David Hunter
Address 53810 0
Royal North Shore Hospital
Rheumatology Department, 7C Clinical Administration
St. Leonards NSW 2065 Australia
Country 53810 0
Australia
Phone 53810 0
+61 2 9463 1887
Fax 53810 0
+61 2 9463 1077
Email 53810 0
david.hunter@sydney.edu.au
Contact person for public queries
Name 53811 0
Dr Sarah Rubia Robbins
Address 53811 0
Royal North Shore Hospital
Rheumatology Department, 7C Clinical Administration
St. Leonards NSW 2065 Australia
Country 53811 0
Australia
Phone 53811 0
+61 2 94631855
Fax 53811 0
+61 2 9463 1077
Email 53811 0
sarah.robbins@sydney.edu.au
Contact person for scientific queries
Name 53812 0
Prof David Hunter
Address 53812 0
Royal North Shore Hospital
Rheumatology Department, 7C Clinical Administration
St. Leonards NSW 2065 Australia
Country 53812 0
Australia
Phone 53812 0
+61 2 9463 1887
Fax 53812 0
+61 2 9463 1077
Email 53812 0
david.hunter@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The study does not have ethics approval to make IPD available.
What supporting documents are/will be available?
Other
'Other' documents specified
Protocol paper
How or where can supporting documents be obtained?
Type [1] 51 0
Other
Citation [1] 51 0
Link [1] 51 0
Email [1] 51 0
Other [1] 51 0
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Yes
Results – basic reporting
Results – plain English summary