ANZCTR - Registration

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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

4/10/2022

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]

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

Condition category

Condition code

Musculoskeletal

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]

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]

change in knee pain : WOMAC pain

Timepoint [1]

3 months

Secondary outcome [1]

Change in WOMAC total

Timepoint [1]

3 months

Secondary outcome [2]

Substantial response: the proportion of participants achieving a substantial response (reduction in pain intensity of >= 50%) at 3 months, measured on VAS (0-100mm).

Timepoint [2]

3 months

Secondary outcome [3]

Moderate response: the proportion of participants achieving a moderate response (reduction in pain intensity of >= 30%) at 3 months, measured on VAS (0-100mm).

Timepoint [3]

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

Sex

Both males and females

Can healthy volunteers participate?

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

Completed

Date of first participant enrolment

Anticipated

7/07/2015

Actual

7/07/2015

Date of last participant enrolment

Anticipated

Actual

2/09/2021

Date of last data collection

Anticipated

30/11/2021

Actual

10/01/2022

Sample size

Target

160

Accrual to date

Final

160

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

The Alfred - Prahran

Recruitment postcode(s) [1]

3004 - St Kilda Road Melbourne

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Human Research Ethics Committee

Ethics committee address [1]

Alfred Human Research Ethics Committee
Alfred Hospital
Commercial Road
Prahran 3181
Vic

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

26/11/2014

Approval date [1]

19/12/2014

Ethics approval number [1]

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

Prof Anita Wluka

Address

Department of Epidemiology and Preventive Medicine
Monash University
Alfred Hospital
Commercial Road
Melbourne VIC 3004

Country

Australia

Phone

+ 61 3 9903 0555

Fax

anita.wluka@monash.edu

Contact person for public queries

Name

Molly Bond

Address

Department of Epidemiology and Preventive Medicine
Monash University
Alfred Hospital
Commercial Road
Melbourne VIC 3004

Country

Australia

Phone

+ 61 3 9903 0553

Fax

jointstudy@monash.edu

Contact person for scientific queries

Name

Anita Wluka

Address

Department of Epidemiology and Preventive Medicine
Monash University
Alfred Hospital
Commercial Road
Melbourne VIC 3004

Country

Australia

Phone

+ 61 3 9903 0555

Fax

anita.wluka@monash.edu

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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 Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Effect of low-dose amitriptyline on reducing pain in clinical knee osteoarthritis compared to benztropine: study protocol of a randomised, double blind, placebo-controlled trial.	2021	https://dx.doi.org/10.1186/s12891-021-04690-y

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically