Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000501842
Ethics application status
Approved
Date submitted
20/02/2012
Date registered
9/05/2012
Date last updated
25/11/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
Train High Eat Low for Osteoarthritis: THE LO Study
Scientific title
A randomised controlled trial of the effects of progressive resistance training, high protein/low glycaemic index diet and gait re-training on knee adductor moment in overweight/obese adults with medial knee osteoarthritis.
Secondary ID [1] 279912 0
Nil known
Universal Trial Number (UTN)
U1111-1128-0932
Trial acronym
THE LO Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis 285821 0
Overweight/Obese 285822 0
Condition category
Condition code
Physical Medicine / Rehabilitation 285999 285999 0 0
Other physical medicine / rehabilitation
Diet and Nutrition 286000 286000 0 0
Obesity
Musculoskeletal 286674 286674 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
We have designed a novel, evidence-based lifestyle modification program which targets most of the treatable aetiological factors in OA: “Train High Eat Low for Osteoarthritis” or THE LO Study). It i s important to study these components in additive fashion, however, a s there are no previous randomised controlled trial (RCT) data on the application of gait training or a low GI/GL diet alone in individuals with knee OA to our knowledge. As we have recently reviewed, there are a large number of randomised controlled trials (RCTs) of isolated resistance training for knee OA, including our own recent trial, and therefore less rationale for studying isolated PRT once again.

Theoretically, each intervention will reduce KAM via a different pathway, and thus we anticipate a dose-response effect with the application of a singular component or all three components of the program.

ARM 1 – GAIT RE-TRAINING (GAIT GROUP)
Pelvic obliquity, trunk lean and insufficient leg flexion have been related to an increase in KAM, while increased medial-lateral sway, widened stance, knee flexion and altered toe position can lower KAM. Recognising that a single gait modification might not suit all participants, however, our strategy will beto ask subjects to adjust their gait in whatever way reduces pain and KAM, while receiving visual feedback reinforcement. The potential effectiveness of this motor learning approach for our proposed gait training intervention is supported by Wishart and Lee, who found that older adults in particular benefit from concurrent augmented visual feedback when learning a bimanual task. Similarly, we have shown that concurrent augmented visual feedback significantly improved patterns of work during an exercise task, compared with no augmented feedback.

Ten trials of participants’ habitual gait will be recorded per 60-90 minute training session. During each of the habitual gait trials, the subject will be provided with visual and verbal feedback of their ground reaction force vector and the significance of the feedback will be explained. The participant will be shown how to alter his/her gait so as to reduce KAM and knee pain, and further gait trials will be recorded while the participant attempts to replicate this modified gait. Participant will be asked to rate the knee pain experienced during the each trial on a Likert pain scale and to report if using the modified gait introduces any other discomfort. Adequate rest will be provided after each trial.

Participants will be asked to practice the new technique at home using a mirror each day for 10 minutes and to try to use the modified gait whenever walking. Home practice of the gait modification will be monitored and supported via a simple logbook, reviewed by educators weekly.

Participants will return to the biomechanics laboratory to gain further feedback about their progress in mastering the pain-reducing gait technique once each week for one month. Over the month the number of trials during which feedback will be provided will be reduced until there is no feedback. Participants will be asked to return to the laboratory once per month for the duration of the 12-mo study for reinforcement and visual feedback of their modified gait.

For each participant, the time series of the net joint forces, moments and powers will be evaluated for all ten trials using Cortex (ver. 2, Motion Analysis Corporation, USA). The research team will discuss the outcomes of this analysis together with the pain scale, post-data collection participant discussion results with the objective of optimising the magnitude of pain and KAM reduction at the participant’s next visit.

ARM 2 – HIGH PROTEIN/LOW GLYCAEMIC LOAD DIET (DIET GROUP)
Participants in this group will be coached to adopt a high protein/low GI weight loss diet. The goal of the diet is to reduce weight by 5-10% over 12 months with a sustainable change in eating patterns and moderate energy restriction similar to the diabetes prevention programs.
The target macronutrient composition is 45% of energy from carbohydrates, emphasising low glycaemic sources, 35% from fat, and 20% from protein. This macronutrient distribution is similar to the average Australian diet, but the GI index is lower. The diet will aim to be as low in GI as practical and achieved by replacing higher GI carbohydrates (e.g., conventional white or wholemeal bread, breakfast cereals, potatoes) with lower GI carbohydrates (e.g., Burgen 'Registered Trademark' grain breads, oats, pasta, Basmati rice). The GI of the low GI/GL diet will be <50 (glucose < 100) and calculated using published data for Australian foods, which has been largely generated by CIB. The diet will emphasise lean sources of protein and restriction of saturated and trans fat (but not total fat).

Individual dietary counselling is necessary to identify current dietary patterns, recommend specific changes, and identify barriers and target behavioural change strategies to the individual successfully. This will be accomplished by having the OA educators meet individually with participants in 60 minute sessions, once per week for the first 4 weeks, then fortnightly for the next 8 visits, then monthly for remainder of the year. Participants will be provided with leaflets that outline the carbohydrate choices and the food amounts that constitute one serving. The OA educators will also provide information on the whole diet to ensure energy and overall nutrient balance and be available for telephone queries outside of scheduled visits. To further encourage dietary adherence, key foods will be provided in the form of a hamper (sample bag).

All participants will be weighed at each diet visit the same calibrated scale at the laboratory, as frequent weighing has been shown to enhance weight loss significantly. The participants will also be asked to weigh themselves each morning and measure their waist circumference once a week using tools we give them, and record this in their logbooks. They will also be asked to complete a 24 hour recall of their food intake once a week. All of these results will be recorded in a pocket-sized log that the participant will keep for the year. These logs will be reviewed each week at the time of weighing by the OA educators. Logging of behaviour and goals has been shown to significantly enhance compliance and weight loss.

At 3, 6 and 12 months, unannounced 24-hour food recall interviews will be conducted in conjunction with collection of 3-day food diaries to assess dietary compliance. Participants who have low adherence (<75%) will receive additional individual booster sessions by the OA educators, in person or by telephone if they are not attending sessions. The behavioural change principles that will be utilised to maximise adherence include the theoretically-grounded principles of decisional balance, social cognitive theory and the stages of change model. Multi-skilled health professional educators with expertise in both the dietary and exercise components of the lifestyle modification program are critical to oversee the intervention and nurture participant perception that these elements are inextricably linked to successful long-term weight control and OA management.

ARM 3 – PROGRESSIVE RESISTANCE TRAINING (PRT GROUP)
Participants assigned to this group will undergo high intensity PRT for 60-90 minutes, 2 times per week for 12 months, including seated leg press, knee extension, knee flexion, standing hip flexion and hip abduction, using Keiser pneumatic strength training equipment, which allows for low impact, and smooth, continuous progressive loading. Sessions will be conducted in small groups supervised by an experienced exercise physiologist. The specific protocol for the strength training has been successfully used in the REACH study (Lange et al, 2009) by our team and is supported by a large RCT evidence base for the use of PRT in knee OA which we have recently reviewed. Legs will be trained unilaterally (3 sets of 8 reps) to maximise isolation of the muscle groups and training adaptations, as well as to customise loads for asymmetry in strength due to underlying arthritis. Initial resistance will be set at 50% of the baseline 1RM, and increased to 80% of participant’s initial 1RM over the first 4 weeks of training. The resistance will be increased progressively at each session by approximately 3% or the appropriate load in order to keep the training intensity between 15 and 18 (HARD) on the Borg scale of Perceived Exertion, modified as needed for joint pain.

ARM 4 – GAIT + DIET + PRT (COMBINED GROUP)
Volunteers assigned to this group will receive all the components of the gait training, progressive resistance training and the high protein / low GI diet intervention. Visits to Lidcombe will offer combined training/educational sessions to minimise burden on the subjects in the combined group.
We expect that, based on ADAPT study (Messier et al, 2004), each of the intervention arms will be more effective than usual care advice, as was shown in ADAPT with diet and/or aerobic exercise vs. usual care. We anticipate that our interventions will be more effective and sustainable than the ADAPT diet and exercise interventions due to their more targeted approach to the pathophysiology of knee OA than standard weight loss diets and walking exercise, and higher efficacy of DIOGENES-type diet compared to low fat, energy restricted weight loss diet.
Intervention code [1] 284236 0
Treatment: Other
Intervention code [2] 284237 0
Lifestyle
Intervention code [3] 284238 0
Behaviour
Comparator / control treatment
ARM 5 – USUAL CARE (CONTROL GROUP)
The Lifestyle Advice control group provides attention, social interaction and general health education in one 60 minute group session completed in the first three months, separated in time and location from the experimental group so as to prevent contamination. An OA educator will provide presentations on a healthy lifestyle including exercise and diet recommendation based on the successful ADAPT exercise and diet intervention. Dietary advice will include a restriction in calorie intake without any specific information on GI index. Weekly phone contact will be maintained on a weekly basis over the 12 months to ensure equal ascertainment of adverse events/health status.
Control group
Active

Outcomes
Primary outcome [1] 286492 0
The primary endpoint for this study will be the change in knee adductor moment (KAM) at 12 months. KAM is assessed in the biomechanics lab at University of Sydney, Cumberland Campus. Reflective markers are placed on the participant who is then asked to perform several walks across a force platform in front of infrared cameras that collect data from the markers.
Timepoint [1] 286492 0
At baseline and 6- and 12-months after intervention commencement.
Primary outcome [2] 286560 0
Peak knee adduction moment during gait at baseline and 6- and 12-months after intervention commencement: KAM and other biomechanical parameters of gait at habitual and maximal velocity and during chair rise will be computed from inverse dynamics analysis of an eight segment body model defined by 32 markers over anatomical landmarks on the trunk, pelvis and lower limbs. Peak KAM has been shown to be highly reproducible, with a mean difference between test sessions of 0.1% normalised for body weight x height. Both absolute and normalised KAM will be of interest, to ascertain what portion of the variance in KAM after intervention is unexplained by weight change.
Timepoint [2] 286560 0
At baseline, 6- and 12-months after intervention commencement.
Secondary outcome [1] 296018 0
Knee Cartilage Thickness Change via Radiography: The project will use the SynaFlexer Frame with innovative image analysis techniques to assess joint space narrowing using fixed flexion standing PA knee radiography as an indirect measure of articular cartilage thickness.
Timepoint [1] 296018 0
At baseline and 12-months after intervention commencement.
Secondary outcome [2] 296170 0
Body composition analysis: DXA scan for whole body and regional muscle and fat and bone mass, with which CIA has extensive experience over 20 yrs.
Timepoint [2] 296170 0
At baseline, 6- and 12-months after intervention commencement.
Secondary outcome [3] 296171 0
Muscle strength: The 1 Repetition Maximum (1RM) Test will be used to determine the dynamic maximal muscle strength. This technique has been used extensively to monitor gains in muscle strength in strength training intervention in older adults and gives a good reliability.
Timepoint [3] 296171 0
At baseline, 6- and 12-months after intervention commencement.
Secondary outcome [4] 296172 0
Pain, stiffness, and physical functional disability: Disease specific symptoms will be evaluated with the Western Ontario and McMaster Universities (WOMAC), internationally accepted as the standard clinical assessment tool in OA and is sensitive to change with interventions.
Timepoint [4] 296172 0
At baseline, 6- and 12-months after intervention commencement.
Secondary outcome [5] 296173 0
Physical Performance: Maximal chair stand, stair climb, balance and 6-minute walk distance.
Timepoint [5] 296173 0
At baseline, 6- and 12-months after intervention commencement.
Secondary outcome [6] 296174 0
Habitual physical activity and sedentary behaviour: Actigraph accelerometers set at 10 s epochs will be worn during all waking hours for 7 days on the non-dominant hip as well as on the non-dominant wrist at all times to monitor sleep quality.
Timepoint [6] 296174 0
At baseline, 6- and 12-months after intervention commencement.
Secondary outcome [7] 296175 0
Nutritional assessment: comprehensive food recall/diary and 24-hour urine sample for assessment of dietary nitrogen.
Timepoint [7] 296175 0
At baseline, 6- and 12-months after intervention commencement.
Secondary outcome [8] 296176 0
Inflammation, metabolism and cartilage turnover: We will measure adipokines and inflammatory markers (serum leptin, serum adiponectin and serum IL-6, hsCRP and orosomucoid levels) and cartilage turnover (serum cartilage oligomeric matrix protein, serum hyaluronic acid, serum N-terminal propeptide of type IIA collagen, serum collagen helical peptide). We will also look at fasting levels of insulin, glucose, LFTs, creatinine and creatinine clearance, total protein, and 24-hour urine creatinine and protein.
Timepoint [8] 296176 0
At baseline, 6- and 12-months after intervention commencement.
Secondary outcome [9] 296177 0
Gait parameters: We will also analyse gait cadence, velocity, step length, range of motion in ankle, knee and hip, and rate of loading. The gait parameters are assessed in the biomechanics lab at University of Sydney, Cumberland Campus. Reflective markers are placed on the participant who is then asked to perform several walks across a force platform in front of infrared cameras that collect data from the markers.
Timepoint [9] 296177 0
At baseline, 6- and 12-months after intervention commencement.

Eligibility
Key inclusion criteria
The following inclusion criteria enable the volunteer to participate in the THE LO Study:
- Primary osteoarthritis of at least one knee
- BMI >27.5 kg/m2
- Aged 40 years or more

Criteria used to make OA diagnosis:
- Knee pain
- +ve at least 1 of 3:
- Age > 50 years
- Stiffness < 30 minutes
- Crepitus
- +ve Osteophytes
- +ve Xray diagnosis (or other previous scans)
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The following conditions permanently exclude the subject from participation in the THE LO STUDY:
- Unstable aortic aneurysm
- Rapidly progressive or terminal illness
- Severe left ventricular dysfunction/end stage congestive heart failure
- Severe aortic stenosis
- Secondary osteoarthritis (traumatic or post-surgical), rheumatic disease, gouty or septic arthritis, Paget's disease, pseudogout, major congenital abnormalities, hemachromatosis, Wilson's disease and other rare forms of arthritis)
- Previous or anticipated (within 6-12 months) joint replacement operation
- Severe psychosis or behavioural disturbance or cognitive impairment
- Surgery to any structure (cartilage, bone, tendons, ligaments, muscle) in or around the knee joint

The following conditions require medical intervention or re-evaluation prior to participation in THE LO Study:
- Abnormal resting ECG
- Angina (unstable)
- Arrhythmias or heart block (uncontrolled)
- Breathing problem or motion disorder
- Cardiac surgery (within last 6 months)
- Cataract extraction (within last month)
- CHF (uncontrolled)
- Cognitive impairment (mild-moderate)
- COPD / CAL (uncontrolled)
- Diabetes (uncontrolled, eg. HbA1c > 10%)
- Deep venous thrombosis (acute)
- Endocarditis
- Fracture (recent or delayed union)
- Haemorrhoids (severe)
- Hernia (unrepaired or symptomatic; abdominal or inguinal)
- Hypertension (uncontrolled; arterial or pulmonary)
- Knee joint injury within the past 6 months
- Knee Injections (e.g. Corticosteroids – cortisone); no more than 2 in the last 5 years, and only one in the last 6 months.
- Myocardial infarction (acute; within last 6 months)
- Neurological disease (rapidly progressive or unstable)
- Pericarditis (acute)
- Pulmonary embolism or infarction (acute)
- Retinopathy, recently treated, unstable
- Severe functional limitation (unable to walk unaided by a person)

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)
Recruitment will primarily be conducted through the physicians at the rheumatology clinics and other departments (including radiology) of the following hospitals:
- Concord Repatriation General Hospital
- Royal Prince Alfred Hospital

Potentially eligible participants will be given flyer detailing the aims of the study, basic eligibility criteria, and a University of Sydney staff member contact number to call if they are interested in participating. Participants who are recruited from one of the Rheumatology Clinics (Concord Hospital, RPA Hospital) may fill in a form requesting to be contacted by a study investigator if they prefer.

Other sources of potential volunteers include:
- Arthritis NSW Website
- Specialist / GP referral
- Newspaper advertisements
- Seniors magazine advertisements
- Databases from previous studies where individuals have indicated that they would like to be contacted for future studies

To assess subject eligibility for THE LO Study, interested volunteers will undergo a telephone screening. The questions on the form were designed to address all inclusion and exclusion criteria. A 30 minute phone call from the interviewer will allow all volunteers to answer the questions and ask any that they may have about the study. All telephone screening questionnaires will be reviewed by the study physicians every week.

Participants will be informed about their eligibility or placed on hold for further medical information and/or investigation(s). An information package will be sent to potentially eligible subjects and will include an appointment to see the study physician, information regarding location of the screening, testing venue, a permission slip for access of medical records, and a brief outline of the assessment procedure. If not eligible, the research team will ask volunteers for permission to keep the volunteer’s contact details in case their situation changes over time and they become eligible at a later date. To obtain medical clarification for volunteers, letters were sent to their respective doctors along with the signed permission slip from the volunteer indicating that the physician may release relevant medical information.

Potentially eligible participants invited to the screening at Lidcombe will be given the participant information statement and an informed consent form at their first visit to the University of Sydney (Lidcombe). They will be guided through all aspects of the information statement and have any questions answered to their satisfaction. Those subjects who agree to participate in the study will be asked to sign the consent form according to guidelines of the Sydney South West Area Health Service and the University of Sydney Human Research Ethics Committees. To determine final eligibility the study physician will examine, consult and review the medical records and telephone screening of each subject.

Eligible subjects will then continue on with the then asked to attend baseline screening days. Screening assessments will take place over two days at The University of Sydney (Lidcombe) and one morning at Concord Repatriation General Hospital (Concord) for a standing knee x-ray. The outcome of the physician screening and knee x-ray form part of the eligibility criteria. Those found to be eligible after the completion of the baseline assessments will be randomised to one of the intervention arms. Where medial knee OA has not been confirmed by x-ray or MRI, participants will need to sign the consent form and complete the xray first.

Once the participant has completed the baseline assessment, he/she is deemed eligible for enrolment. The holder of the allocation schedule is located off-site and is contacted for participant allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Concealed randomisation will be prepared by an offsite research assistant not involved in testing/training, using a computer-generated random number sequence. Participants will be stratified according to gender and BMI <35 or >35 kg/m2. Sequential treatment allocations will be enclosed in numbered, opaque sealed envelopes, and distributed by this research assistant to each participant after completion of the baseline assessment.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/02/2012
Actual
9/09/2011
Date of last participant enrolment
Anticipated
30/04/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
125
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 284742 0
Government body
Name [1] 284742 0
National Health and Medical Research Council
Country [1] 284742 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Faculty of Health Science
Exercise, Health and Performance Research Group
75 East St
Lidcombe NSW 2141
Country
Australia
Secondary sponsor category [1] 283635 0
Hospital
Name [1] 283635 0
Concord Repatriation General Hospital
Address [1] 283635 0
Hospital Rd
Concord NSW 2139
Country [1] 283635 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286747 0
Concord Repratriation General Hospital Human Research Ethics Committee
Ethics committee address [1] 286747 0
Ethics committee country [1] 286747 0
Australia
Date submitted for ethics approval [1] 286747 0
Approval date [1] 286747 0
08/04/2011
Ethics approval number [1] 286747 0
HREC/11/CRGH/47

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33758 0
Prof Maria Fiatarone Singh
Address 33758 0
The University of Sydney Faculty of Health Sciences Exercise, Health & Performance Faculty Research Group Room K221, 75 East St Lidcombe NSW 2141
Country 33758 0
Australia
Phone 33758 0
+61 2 9351 9755
Fax 33758 0
+61 2 9036 7400
Email 33758 0
[email protected]
Contact person for public queries
Name 17005 0
Yareni Guerrero
Address 17005 0
The University of Sydney
Faculty of Health Sciences
Exercise, Health & Performance Faculty Research Group Room C113, 75 East St
Lidcombe NSW 2141
Country 17005 0
Australia
Phone 17005 0
+61 2 9351 9826
Fax 17005 0
+61 2 9036 7400
Email 17005 0
[email protected]
Contact person for scientific queries
Name 7933 0
Prof Maria Fiatarone Singh
Address 7933 0
The University of Sydney
Faculty of Health Sciences
Exercise, Health & Performance Faculty Research Group Room K221, 75 East St
Lidcombe NSW 2141
Country 7933 0
Australia
Phone 7933 0
+61 2 9351 9755
Fax 7933 0
+61 2 9351 9204
Email 7933 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseTrain High Eat Low for Osteoarthritis study (THE LO study): protocol for a randomized controlled trial.2015https://dx.doi.org/10.1016/j.jphys.2015.05.020
N.B. These documents automatically identified may not have been verified by the study sponsor.