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Trial registered on ANZCTR


Registration number
ACTRN12617001524381
Ethics application status
Approved
Date submitted
28/07/2017
Date registered
2/11/2017
Date last updated
6/05/2021
Date data sharing statement initially provided
6/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised trial of colchicine for osteoarthritis of the hand (COLAH)
Scientific title
A randomised trial of colchicine for reducing osteoarthritis-related pain in the hand (COLAH)
Secondary ID [1] 291981 0
Nill known
Universal Trial Number (UTN)
U1111-1199-9761
Trial acronym
COLAH
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Hand Osteoarthritis
 303333 0
Condition category
Condition code
Musculoskeletal 302767 302767 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Colchicine , Oral Tablet, 0.5mg, twice daily.
Duration of administration, 12 weeks
To monitor adherence, at the week 6 phone call participants will be asked to count their remaining pills to determine how many have been taken.
All pill packets will be returned at week 12 visit to determine left over pills.
Intervention code [1] 298106 0
Treatment: Drugs
Comparator / control treatment
identical placebo (cellulose) Oral Tablet, twice daily
Control group
Placebo

Outcomes
Primary outcome [1] 302155 0
VAS pain scores
Timepoint [1] 302155 0
0 weeks, 6 weeks, 12 weeks and 16 weeks
Secondary outcome [1] 334982 0
AUSCAN score
Timepoint [1] 334982 0
0 weeks, 6 weeks, 12 weeks and 16 weeks
Secondary outcome [2] 340227 0
Ultrasound measured synovitis
Timepoint [2] 340227 0
0 weeks and 12 weeks
Secondary outcome [3] 340228 0
Adverse effects (measured by patient report, renal, haematological and hepatic function)
Timepoint [3] 340228 0
Week 6, Week 12 and Week 16
Secondary outcome [4] 380976 0
C-reactive protein (from blood samples) at week 0 and week 12
Timepoint [4] 380976 0
Week 12
Secondary outcome [5] 380977 0
Grip strength measured by dynamometer at week 0 and week 12.
Timepoint [5] 380977 0
Week 12
Secondary outcome [6] 380978 0
Number of tender joints of affected hand at week 0 and week 12
Timepoint [6] 380978 0
Week 12
Secondary outcome [7] 380979 0
Number of swollen joints at week 0 and week 12
Timepoint [7] 380979 0
Week 12

Eligibility
Key inclusion criteria
1) Aged between 40 and 80 years old
2) Men and women with significant hand pain within the last 48 hours (defined as a VAS greater than or equal to 40 mm) with a history of Hand pain for minimum of 6 months.
3) Radiological OA (Kellgren and Lawrence (KL) grade > 1) in > 1 joint
4) Meet American College of Rheumatology (ACR) clinical criteria for hand OA
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Concomitant inflammatory rheumatic disease
2. Contraindication to colchicine. This includes renal dysfunction (eGFR <50, abnormal LFT, haematologic condition
3. Chronic glucocorticoid, DMARD or immunosuppressant therapy for arthritis or other indications
4. Women who are pregnant or breast feeding
5. Use of any investigational drug(s) and/or devices within 30 days prior to randomisation
6. Presence of any serious medical illness that may preclude 24 week follow up.
7. Inability to provide informed consent.

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)
Central randomisation by computer at the clinical trial pharmacy
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
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
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
An intention-to-treat approach will be taken, consistent with CONSORT guidelines. Baseline characteristics between groups will be analysed by unpaired t test. For the primary endpoint, we will use a random intercept longitudinal regression model over each time point, with the constraint that the baseline means for the two groups are equal. Safety data will be analysed by means of descriptive statistics. Subgroup analysis will be performed for those participants with synovitis identified by ultrasound (exploratory analysis)


Sample Size
The average VAS in a previous RCT of symptomatic hand OA similar to the proposed study was 67.1mm (standard deviation 13.1mm). With 31 in each group, the study will have 80% power to detect a VAS pain difference of 10mm, including projected 10% drop-out rate.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
20/11/2017
Actual
20/03/2018
Date of last participant enrolment
Anticipated
31/12/2018
Actual
10/10/2019
Date of last data collection
Anticipated
30/04/2019
Actual
30/01/2020
Sample size
Target
62
Accrual to date
Final
61
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 8030 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 16017 0
5011 - Woodville

Funding & Sponsors
Funding source category [1] 296491 0
Charities/Societies/Foundations
Name [1] 296491 0
The Hospital Research Foundation
Country [1] 296491 0
Australia
Primary sponsor type
Individual
Name
Dr Catherine Hill
Address
Rheumatology Clinical Trials
TQEH, Level 5C
28 Woodville Road
Woodville South, SA 5011
Country
Australia
Secondary sponsor category [1] 295449 0
Charities/Societies/Foundations
Name [1] 295449 0
Arthritis Australia
Address [1] 295449 0
Arthritis Australia
Level 2/255 Broadway
GLEBE NSW 2037
Country [1] 295449 0
Australia
Secondary sponsor category [2] 296923 0
Charities/Societies/Foundations
Name [2] 296923 0
The Hospital Research Foundation
Address [2] 296923 0
60 Woodville Rd, Woodville, SA 5011
Country [2] 296923 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297711 0
HREC of The Queen Elizabeth Hospital. (TQEH/LMH/MH)
Ethics committee address [1] 297711 0
The Queen Elizabeth Hospital
Ethics: DX465101
Ground Floor, Basil Hetzel Institute
28 Woodville Road
WOODVILLE SOUTH SA 5011
Ethics committee country [1] 297711 0
Australia
Date submitted for ethics approval [1] 297711 0
16/11/2016
Approval date [1] 297711 0
01/06/2017
Ethics approval number [1] 297711 0
HREC/16/TQEH/261

Summary
Brief summary
BACKGROUND: Osteoarthritis (OA) is the most common joint disease and frequently involves the hand. Painful hand OA is associated with a significant disease burden and reduced quality of life. Indeed, the effect of symptomatic hand OA on quality of life is comparable to rheumatoid arthritis, but affects considerably more people (prevalence ~20% versus ~1% in older adults). With an ageing population, the burden and health-care costs related to hand OA will increase. Patients often rely on NSAIDs or opiates with concomitant adverse effects in this age group to control pain. Hand OA is a heterogeneous condition with approximately 50% of patients having evidence of synovitis. This phenotype of hand OA with inflammatory signs i.e. those with evidence of synovitis is associated with increased pain. In addition, hand OA joints with synovitis are 3.5 times more likely to experience rapid joint destruction and radiographic progression than those without synovitis. Ultrasound (US) has been shown to reliably detect synovitis in the joints of the hand when performed by an experienced technician. Therefore, this is the subgroup of patients with hand OA that are most in need of evidence-based therapies. Previous study to assess treatments for hand OA using of plaquenil, etanercept or adalimumab found not superior to placebo to alleviate pain. There is possible effect if structural modification with etanercept and adalimumab has been shown to be beneficial in erosive and inflamed hand OA. The cost however of these medications in 20K/per year, therefore there use is an expensive alternative.

Currently, there are no proven pharmacological treatments for hand OA. The lack of categorization of hand OA according to inflammatory phenotype may have contributed to previous negative outcomes in clinical trials. Cost-effective therapies targeting synovitis may offer a novel approach for reducing disease burden from hand OA.

Colchicine is a low cost drug which has long been used in the anti-inflammatory treatment of acute gout. There has been recent renewed interest in this ancient drug, particularly its effects in cardiovascular diseases such as pericarditis. The primary mechanism of action of colchicine is tubulin disruption leading to subsequent down-regulation of multiple inflammatory pathways and modulation of innate immunity. Preliminary studies in knee OA have indicated that colchicine may have a beneficial effect on pain and a larger randomized clinical trial of colchicine in knee OA is currently underway. No studies of colchicine have been undertaken in hand OA.

STUDY AIMS
Primary hypothesis:
Colchicine decreases pain (assessed by 100mm VAS) by 10mm more than identical placebo over 12 weeks in patients with clinical hand OA.

STUDY DESIGN
Randomised, placebo-controlled double-blind clinical trial.
This study will be carried out at The Queen Elizabeth Hospital and Royal Adelaide Hospital.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1925 1925 0 0
/AnzctrAttachments/372964-Approval Letter - Q20161109 - Hill.pdf (Ethics approval)
Attachments [2] 1926 1926 0 0
/AnzctrAttachments/372964-ColchicineprotocolbookTQEH.V3, 30MAY 2017 clean.docx (Protocol)
Attachments [3] 1927 1927 0 0
/AnzctrAttachments/372964-COLAH_PICF -V3, 30th MAY 2017_clean.docx (Participant information/consent)

Contacts
Principal investigator
Name 74914 0
Prof Catherine Hill
Address 74914 0
TQEH, Level 5C
28 Woodville Rd
Woodville, 5011
South Australia
Country 74914 0
Australia
Phone 74914 0
+61 8 8222 6688
Fax 74914 0
Email 74914 0
[email protected]
Contact person for public queries
Name 74915 0
Carlee Ruediger
Address 74915 0
TQEH, Level 5C
28 Woodville rd
Woodville, 5011
South Australia
Country 74915 0
Australia
Phone 74915 0
+61 8 8222 7369
Fax 74915 0
Email 74915 0
[email protected]
Contact person for scientific queries
Name 74916 0
Catherine Hill
Address 74916 0
TQEH, Level 5C
28 Woodville rd
Woodville, 5011
South Australia
Country 74916 0
Australia
Phone 74916 0
+61 8 8222 6688
Fax 74916 0
Email 74916 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the individual participant data collected during the trial, after de-identification.
When will data be available (start and end dates)?
Immediately following publication of results, without an end date
Available to whom?
At the discretion of the principle investigator, upon application.
Available for what types of analyses?
This will be assessed on a case by case basis, likely meta-analyses would be acceptable.
How or where can data be obtained?
From the principle investigator upon request.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
7266Study protocol    372964-(Uploaded-28-10-2019-14-34-25)-Study-related document.docx



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseColchicine is not effective for reducing osteoarthritic hand pain compared to placebo: A randomised, placebocontrolled trial (COLAH).2020https://dx.doi.org/10.1111/imj.14932
EmbaseColchicine is not effective for reducing osteoarthritic hand pain compared to placebo: a randomised, placebo-controlled trial (COLAH).2021https://dx.doi.org/10.1016/j.joca.2020.11.002
N.B. These documents automatically identified may not have been verified by the study sponsor.