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Trial registered on ANZCTR


Registration number
ACTRN12615000301561
Ethics application status
Approved
Date submitted
19/03/2015
Date registered
31/03/2015
Date last updated
14/12/2018
Date data sharing statement initially provided
14/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Does amitriptyline reduce pain in knee osteoarthritis?
Scientific title
Does low dose amitriptyline reduce pain in knee osteoarthritis? A double blind, randomised, pragmatic, placebo controlled clinical trial of amitriptyline compared to active placebo in addition to usual care
Secondary ID [1] 286336 0
Nil
Universal Trial Number (UTN)
U1111-1168-1721
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Painful knee osteoarthritis 294452 0
Condition category
Condition code
Musculoskeletal 294757 294757 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Low-dose amitriptyline; 25mg; to be taken by mouth, in capsule form, alternate days for 2 weeks, then daily administration; 3 month duration

Bottles will be returned at the end of the study to assess compliance.
Intervention code [1] 291390 0
Treatment: Drugs
Comparator / control treatment
Benztropine 1mg: to be taken by mouth, in capsule form, on alternate days for 2 weeks then daily administration: 3 months duration

Bottles will be returned at the end of the study to assess compliance.

This is an active placebo
Control group
Placebo

Outcomes
Primary outcome [1] 294514 0
change in knee pain : WOMAC pain
Timepoint [1] 294514 0
3 months
Secondary outcome [1] 313544 0
Change in WOMAC total
Timepoint [1] 313544 0
3 months
Secondary outcome [2] 313545 0
OA Research Society International (OARSI) response criteria
Timepoint [2] 313545 0
3 months

Eligibility
Key inclusion criteria
1) Males and females with symptomatic knee OA for at least 3 months, defined by the ACR clinical and radiographic criteria (ie pain and radiographic OA) (Altman, R., et al., Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. . Arthritis Rheum, 1986. 29(8): p. 1039-49.)
2) Pain score of at least 30 mm on a 100 mm visual analogue scale (VAS);
3) Age > 40 years, and < 75 years old
Minimum age
40 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Inability to give informed consent;
2) Intra articular therapy over the past 3 months; Planning knee injection or surgical intervention in the next 4 months
3) Patients with rheumatoid arthritis, other inflammatory arthritis, or significant knee injury;
4) Patients with major depressive disorder for whom anti-depressant therapy is indicated
5) Patients taking medications that are contra-indicated when taking amitriptyline (monoamine oxidase inhibitors, other antidepressants, opioids, drugs that inhibit CYP3A4, etc)
6) Co-morbidity that may limit participation (e.g. any planned joint replacement in the next 4 months, medical conditions e.g. malignancy in the past 5 years other than non-melanoma skin cancer) or relocation;
7) Fibromyalgia, as this is evidence of an alternative underlying explanatory condition
8) Patients with contraindications to amitriptyline therapy eg acute angle glaucoma, prostatism,etc

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)
Allocation concealment will be ensured by the use of identical, active placebo, and the use of a central automated allocation procedure, with security in place to ensure allocation data cannot be accessed or influenced by any person.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization will be performed by a computerised random number generator, that will be held by an independent researcher not involved in other aspects of the trial.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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)
VIC
Recruitment hospital [1] 3560 0
The Alfred - Prahran
Recruitment postcode(s) [1] 9365 0
3004 - St Kilda Road Melbourne

Funding & Sponsors
Funding source category [1] 290912 0
Government body
Name [1] 290912 0
National Health and Medical Research Council
Address [1] 290912 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 290912 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Department of Epidemiology and Preventive Medicine
School of Public Health and Preventive Medicine
Monash University
Alfred Hospital
Commercial Road
Melbourne Vic 3004
Country
Australia
Secondary sponsor category [1] 289592 0
None
Name [1] 289592 0
Address [1] 289592 0
Country [1] 289592 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292512 0
Alfred Human Research Ethics Committee
Ethics committee address [1] 292512 0
Alfred Human Research Ethics Committee
Alfred Hospital
Commercial Road
Prahran 3181
Vic
Ethics committee country [1] 292512 0
Australia
Date submitted for ethics approval [1] 292512 0
26/11/2014
Approval date [1] 292512 0
19/12/2014
Ethics approval number [1] 292512 0
512/14

Summary
Brief summary
Knee osteoarthritis is one of the most common forms of arthritis. Pain, the main symptom, is poorly controlled by current treatment strategies. Pain is thought initially to originate from structural changes in an affected joint. However, after a while, in some people, changes occur in the nervous system that perpetuate the pain. These changes are referred to as pain sensitisation. They are not addressed by current treatments.
Amitriptyline is commonly used to treat pain related to pain sensitisation, such as in shingles or diabetic neuropathy.
This study is a randomised controlled trial of the use of amitriptyline, in addition to usual care, to manage pain in people with painful knee osteoarthritis.
People with knee osteoarthritis will be randomised to receiving low dose amitriptyline or a placebo with many of the same side effects of the active drug, benztropine. They will be followed for 12 weeks to determine the effect of amitriptyline on pain, function and other symptoms of knee osteoarthritis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 55662 0
A/Prof Anita Wluka
Address 55662 0
Department of Epidemiology and Preventive Medicine
Monash University
Alfred Hospital
Commercial Road
Melbourne VIC 3004
Country 55662 0
Australia
Phone 55662 0
+ 61 3 9903 0555
Fax 55662 0
Email 55662 0
anita.wluka@monash.edu
Contact person for public queries
Name 55663 0
Ms Molly Bond
Address 55663 0
Department of Epidemiology and Preventive Medicine
Monash University
Alfred Hospital
Commercial Road
Melbourne VIC 3004
Country 55663 0
Australia
Phone 55663 0
+ 61 3 9903 0553
Fax 55663 0
Email 55663 0
jointstudy@monash.edu
Contact person for scientific queries
Name 55664 0
A/Prof Anita Wluka
Address 55664 0
Department of Epidemiology and Preventive Medicine
Monash University
Alfred Hospital
Commercial Road
Melbourne VIC 3004
Country 55664 0
Australia
Phone 55664 0
+ 61 3 9903 0555
Fax 55664 0
Email 55664 0
anita.wluka@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Study participants were not asked to provide consent for data sharing to occur. This study was initiated in 2014.
What supporting documents are/will be available?
No other documents available
Summary results
No Results