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Trial registered on ANZCTR


Registration number
ACTRN12614000098639
Ethics application status
Approved
Date submitted
22/01/2014
Date registered
28/01/2014
Date last updated
3/11/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
The maximum tolerated dose of walking for people with osteoarthritis of the knee: a phase I trial
Scientific title
Determining the maximum tolerated dose of prescribed physical activity (in the form of walking) for people with severe osteoarthritis of the knee in the community in terms of safety and feasibility
Secondary ID [1] 283961 0
Nil
Universal Trial Number (UTN)
U1111-1152-4646
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
knee osteoarthritis 290991 0
Condition category
Condition code
Musculoskeletal 291334 291334 0 0
Osteoarthritis
Physical Medicine / Rehabilitation 291351 291351 0 0
Physiotherapy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a phase I dose-response trial to find out how much physical activity, in the form of walking, can be prescribed for people with knee osteoarthritis in terms of safety and feasibility.
Groups of 3 participants will be individually supervised to walk at a prescribed level of physical activity over one week. This prescribed level of physical activity will not change for individual participants but may escalate for subsequent groups of participants.
The walking doses will be in minutes per week, of at least moderate intensity, in a minimum of 10 minute bouts, so that the doses can be compared with the current physical activity guidelines.
The dose level of prescribed physical activity will follow a modified Fibonacci scheme starting with an initial dose of 10 minutes per week of moderate intensity supervised walking for the first group of participants.
Moderate intensity walking will be defined as a 3 on the modified Borg 0-10 perceived exertion scale, where 3 = “I am still comfortable but am breathing a little harder.”
Dose escalation will depend on the presence or absence of adverse incidents among the group of 3 participants.
Depending on the feasibility and safety of the prescribed dose of walking, the dose may or may not be escalated between subsequent groups of participants.
Dose escalation will start with early larger dose increments between groups which get smaller for higher doses until the guideline stopping value of 150 minutes of walking per week is reached (i.e. 10, 20, 35, 50, 70, 95, 120, 150 mins)
The trial will stop when/if a group of participants can achieve 150 minutes of prescribed walking as this reflects physical activity guidelines.
Intervention code [1] 288649 0
Rehabilitation
Comparator / control treatment
There will be no control group but the trial will involve dose comparison. The first group of participants will walk for 10 minutes per week. Depending on feasibility and safety, the dose of walking will escalate between groups of participants following a modified Fibonacci scheme of 10, 20, 35, 50, 70, 95, 120 and 150 minutes of walking per week.
Control group
Dose comparison

Outcomes
Primary outcome [1] 291324 0
(1) An estimation of the maximum tolerated dose for prescribed walking for people with severe knee osteoarthritis
Timepoint [1] 291324 0
The maximum tolerated dose of physical activity will be identified when either:
- groups of participants can no longer safely and feasibly complete the prescribed dose of walking
- a group of participants achieves 150 minutes per week of prescribed walking (as dose escalation will not continue as this value reflects physical activity guidelines)
Primary outcome [2] 291350 0
(2) the proportion of people with severe knee osteoarthritis that do not complete the prescribed walking dose for feasibility reasons (i.e. reason other than safety).
Timepoint [2] 291350 0
The proportion of people with severe knee osteoarthritis that do not complete the prescribed walking dose for feasibility reasons (i.e. reason other than safety) will be identified when either:
- groups of participants can no longer safely and feasibly complete the prescribed dose of walking
- a group of participants achieves 150 minutes per week of prescribed walking (as dose escalation will not continue as this value reflects physical activity guidelines)
Secondary outcome [1] 306528 0
Pain, stiffness and activity limitation using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
Timepoint [1] 306528 0
Day 1
Day 7
Secondary outcome [2] 306529 0
Pain measured on an 11 point Numerical Pain Rating Scale
Timepoint [2] 306529 0
1. Start of each walking bout
2. During each walking bout at 5 minute intervals
3. 2 hours after each walking bout
Secondary outcome [3] 306530 0
Physical activity measures of cadence, number of steps and distance covered during the walking bout will be measured using an electronic pedometer worn by the participant
Timepoint [3] 306530 0
Day 7 - average for each walking bout

Eligibility
Key inclusion criteria
(1) Adult aged at least 50 years and living independently in the community;
(2) diagnosed with moderate-to-severe knee osteoarthritis rated as grade III or IV;
(3) able to understand English;
(4) able to participate safely in the moderate-intensity physical activity trial using the 7-item Physical Activity Readiness Questionnaire.
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) live in supported accommodation such as a nursing home;
(2) they report their daily resting level of pain to be 9 or 10 on an 11 point Numerical Pain Rating Scale. This level of pain may be indicative of a more serious pathology such as acute or inflammatory condition;
(3) high or very high levels of psychological distress as measured by the Kessler 10 questionnaire with a K10 score > 21;
(4) have an intellectual or mental impairment as measured by the Short Portable Mental Status Questionnaire with a score of 7 or less;
(5) have a systemic arthritic condition such as rheumatoid arthritis;
(6) have a neurological condition such as Parkinson’s disease or stroke that affects walking;
(7) had knee surgery or intra-articular corticosteroid injection within past six months;
(8) currently (within four weeks) using oral corticosteroids.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
This is a non-randomised trial. The trial will be a phase I dose-response study using the 3+3 design (Gao et al 2008, Lin and Shih 2001).

Patients will be recruited consecutively and allocated to a prescribed physical activity dose.

The dose level of prescribed physical activity will follow a modified Fibonacci scheme starting with an initial dose of 10 minutes of supervised walking per week for the first group of participants, with early larger dose increments which get smaller for higher doses until the guideline stopping value of 150 minutes of walking per week is reached. Prescribed
walking doses will be 10, 20, 35, 50, 70, 95, 120, 150 mins.

Dose escalation will depend on the presence or absence of adverse incidents.

150 minutes is the maximum minutes of prescribed walking per week because if this is achieved without incident it means that participants can safely meet physical activity guidelines for older adults.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
This is a non-randomised trial.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
This is a phase I dose-response trial.
Groups will be dose comparison.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
The primary analysis of the maximum tolerated dose in terms of minutes of moderate intensity physical activity per week will be based on the decision rules by Lin et al 2001.

The primary analysis of the feasibility will be based on the proportion of participants that not able to complete the prescribed dose for feasibility reasons.

The secondary analyses will describe the sample of participants in terms of pain levels, stiffness, activity limitation and physical activity associated with the prescribed doses and the maximum tolerated dose.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
6/01/2014
Actual
8/01/2014
Date of last participant enrolment
Anticipated
1/05/2014
Actual
8/04/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
45
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1990 0
Box Hill Hospital - Box Hill
Recruitment hospital [2] 1991 0
Maroondah Hospital - Ringwood East
Recruitment postcode(s) [1] 7715 0
3128 - Box Hill
Recruitment postcode(s) [2] 7716 0
3135 - Ringwood East

Funding & Sponsors
Funding source category [1] 288594 0
Hospital
Name [1] 288594 0
Eastern Health
Country [1] 288594 0
Australia
Primary sponsor type
Individual
Name
Jason Wallis
Address
Box Hill Hospital
Physiotherapy department - Level 3
Nelson Rd
Box Hill, VIC 3128
Country
Australia
Secondary sponsor category [1] 287301 0
Individual
Name [1] 287301 0
Nicholas Taylor
Address [1] 287301 0
Physiotherapy Department
La Trobe University
Bundoora VIC 3086
Country [1] 287301 0
Australia
Secondary sponsor category [2] 287302 0
Individual
Name [2] 287302 0
Kate Webster
Address [2] 287302 0
La Trobe University
Bundoora VIC 3086
Country [2] 287302 0
Australia
Secondary sponsor category [3] 287303 0
Individual
Name [3] 287303 0
Pazit Levinger
Address [3] 287303 0
Institute of Sport, Exercise & Active Living (ISEAL),
Victoria University
Melbourne VIC 8001
PO Box 14428
Country [3] 287303 0
Australia
Secondary sponsor category [4] 287304 0
Individual
Name [4] 287304 0
Chris Fong
Address [4] 287304 0
5 Arnold Street
Box Hill Hospital
Vic 3128
Country [4] 287304 0
Australia
Secondary sponsor category [5] 287305 0
Individual
Name [5] 287305 0
Parminder Singh
Address [5] 287305 0
Maroondah Hospital
Davey Dr,
Ringwood East
VIC 3135
Country [5] 287305 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290457 0
Eastern Health Research and Ethics Committee
Ethics committee address [1] 290457 0
Level 3, 5 Arnold Street
Box Hill
VIC 3128
Ethics committee country [1] 290457 0
Australia
Date submitted for ethics approval [1] 290457 0
Approval date [1] 290457 0
03/12/2013
Ethics approval number [1] 290457 0
E08 - 1314
Ethics committee name [2] 290458 0
La Trobe University Human Ethics Committee
Ethics committee address [2] 290458 0
Human Ethics Committee
La Trobe University
Bundoora
VIC 3086
Ethics committee country [2] 290458 0
Australia
Date submitted for ethics approval [2] 290458 0
Approval date [2] 290458 0
05/12/2013
Ethics approval number [2] 290458 0
E08 - 1314

Summary
Brief summary
Lack of physical activity is a major health issue for people with osteoarthritis of the knee leading to increased risks of
cardiovascular disease. Only about 1 in 10 people with knee osteoarthritis meets the current physical activity guidelines of at least 150 minutes of moderate intensity activity in minimum of 10 minute bouts each week. It is not known if it is safe or feasible to encourage these people to increase their physical activity level as recommended in the guidelines. This project will determine how much physical activity in the form of walking can be safely and feasibly prescribed for people with severe knee osteoarthritis in the community. Patients that attend the orthopaedic outpatients department at Eastern Health will be invited to participate. We will apply methods commonly used in drug trials to work out how much of a medication can be safely prescribed, but apply these methods to physical activity to work out the maximum tolerated dose of walking for people with severe knee osteoarthritis. The project will begin with prescribing small doses of walking, and measuring the participants’ responses to determine if the prescribed dose is tolerated safely. For example, the walking dose may cause substantial knee pain for the participant that does not settle quickly with rest. This response is termed an adverse or undesired event. If there are no adverse events, the prescribed dose of walking will be escalated in the next independent group of participants until the maximum tolerated dose is reached. This is a phase I dose response trial to characterise the safety profile of a treatment. The outcome of this study will provide evidence for the level of physical activity that can be safely tolerated by people with knee osteoarthritis, and assist health professionals to prescribe safe amounts of walking.
Trial website
Trial related presentations / publications
Wallis JA, Webster KE, Levinger P, Fong C, Singh PJ, Taylor NF. The maximum tolerated dose of walking for people with severe osteoarthritis of the knee: a phase I trial, Osteoarthritis Cartilage 2015;23:1285-93.
Public notes

Contacts
Principal investigator
Name 45790 0
Mr Jason Wallis
Address 45790 0
Box Hill Hospital
Physiotherapy Department - level 3
Nelson Rd
Box Hill, VIC 3128
Country 45790 0
Australia
Phone 45790 0
+61 3 98953715
Fax 45790 0
Email 45790 0
[email protected]
Contact person for public queries
Name 45791 0
Jason Wallis
Address 45791 0
Box Hill Hospital
Physiotherapy Department - level 3
Nelson Rd
Box Hill, VIC 3128
Country 45791 0
Australia
Phone 45791 0
+61 3 98953715
Fax 45791 0
Email 45791 0
[email protected]
Contact person for scientific queries
Name 45792 0
Jason Wallis
Address 45792 0
Box Hill Hospital
Physiotherapy Department - level 3
Nelson Rd
Box Hill, VIC 3128
Country 45792 0
Australia
Phone 45792 0
+61 3 98953715
Fax 45792 0
Email 45792 0
[email protected]

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