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Trial registered on ANZCTR


Registration number
ACTRN12618000080224
Ethics application status
Approved
Date submitted
9/01/2018
Date registered
19/01/2018
Date last updated
4/06/2019
Date data sharing statement initially provided
4/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised trial of Curcuma longa for treating symptoms and effusion-synovitis of knee osteoarthritis.
Scientific title
A randomised trial of Curcuma longa for treating symptoms and effusion-synovitis of knee osteoarthritis.
Secondary ID [1] 292597 0
None
Universal Trial Number (UTN)
U1111-1200-3803
Trial acronym
CurKOA Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis 304287 0
Condition category
Condition code
Musculoskeletal 303635 303635 0 0
Osteoarthritis
Alternative and Complementary Medicine 305298 305298 0 0
Herbal remedies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
35 patients with clinical knee osteoarthritis, significant knee pain and effusion-synovitis on imaging will receive 1g (2 capsules of 500mg each) of Curcuma longa extract per day for 12 weeks. Adherence to treatment will be monitored by counting the returned capsules at the 12 week visit.
Intervention code [1] 298820 0
Treatment: Other
Comparator / control treatment
35 patients with clinical knee osteoarthritis, significant knee pain and effusion-synovitis on imaging will receive 1g (2 capsules of 500mg each) of inert placebo (microcrystalline cellulose capsules) per day for 12 weeks. Adherence to treatment will be monitored by counting the returned capsules at the 12 week visit.
Control group
Placebo

Outcomes
Primary outcome [1] 302994 0
Change in knee pain (assessed by 100mm VAS) over 12 weeks in patients with clinical knee OA
Timepoint [1] 302994 0
Mixed model accounting for the overall change (slope of the knee pain graph from baseline
though weeks 4, 8 and ending at week 12) in knee pain from baseline.
Primary outcome [2] 302995 0
Change in effusion-synovitis size from baseline to 12 weeks measured using MRI quantitative measurements in patients with symptomatic OA of the knee and knee effusion-synovitis.
Timepoint [2] 302995 0
MR Imaging at baseline and week 12
Secondary outcome [1] 337655 0
Change in WOMAC knee pain (total, weight bearing and non-weight bearing) from baseline to 4, 8 and 12 weeks in patients with clinical knee OA , significant knee pain and effusion-synovitis.
Timepoint [1] 337655 0
Baseline and weeks 4, 8 and 12.
Secondary outcome [2] 337656 0
Change in WOMAC knee function (assessed by WOMAC scoring system) from baseline to 4, 8 and 12 weeks in patients with clinical knee OA, significant pain and effusion-synovitis.
Timepoint [2] 337656 0
Baseline and weeks 4, 8 and 12.
Secondary outcome [3] 337657 0
Change in T1p and T2 mapping values (cartilage composition measured using MRI) from baseline to week 12 in patients with clinical knee OA, significant pain and effusion-synovitis.
Timepoint [3] 337657 0
Baseline and week 12.
Secondary outcome [4] 337658 0
Change in physical function as assesed by 30s Chair Stand Test, 40m Fast Walk Test and Stair Climb Test in patients from baseline to week 12 with clinical knee OA, significant pain and effusion-synovitis.
Timepoint [4] 337658 0
Baseline and week 12.
Secondary outcome [5] 337659 0
OMERACT_OARSI responders (20% improvement in WOMAC pain) at week 4, 8 and 12 in patients with clinical knee OA, significant pain and effusion-synovitis.
Timepoint [5] 337659 0
Baseline and weeks 4, 8 and 12.
Secondary outcome [6] 337660 0
Change in cartilage breakdown biomarkers (urinary CTX-II, serum COMP and serum hyaluronan) from baseline to week 12 in patients with clinical knee OA, significant pain and effusion-synovitis. These biomarkers will be assessed from urine and serum samples collected at baseline and 12 weeks.
Timepoint [6] 337660 0
Baseline and week 12.
Secondary outcome [7] 337661 0
Change in systemic inflammatory markers (hs-CRP, IL-6, TNF-a) from baseline to week 12 in patients with clinical knee OA, significant pain and effusion-synovitis. These biomarkers will be assessed from serum samples collected at baseline and 12 weeks.
Timepoint [7] 337661 0
Baseline and week 12.
Secondary outcome [8] 337662 0
Change in concomitant medications (assessed using self-reported medication history questionnaire) from screening to weeks 4, 8 and 12 in patients with clinical knee OA, significant pain and effusion-synovitis.
Timepoint [8] 337662 0
Screening and weeks 4, 8 and 12.
Secondary outcome [9] 337663 0
Change in quality of life (assessed by AQoL-15) from baseline to week 12 in patients with clinical knee OA, significant pain and effusion-synovitis.
Timepoint [9] 337663 0
Baseline and week 12.
Secondary outcome [10] 337664 0
Curcuma Longa is a very safe medication, with no major side effects attributable to the drug. Curcuma Longa treatments in clinical trials have reported gastrointestinal symptoms including dyspepsia and regurgitation. However, the control groups such as placebo and pain medicine (ibuprofen and diclofenac) also showed similar adverse effects.

The difference in adverse events reported (using adverse event form filled by a research nurse and reviewed by a physician) at week 4, 8 and 12 in patients with clinical knee OA, significant pain and effusion-synovitis.
Timepoint [10] 337664 0
Weeks 4, 8 and 12.
Secondary outcome [11] 341807 0
Change in synovitis volume (synovitis measured using contrast-enhanced MRI) from baseline to week 12 in patients with clinical knee OA, significant pain and effusion-synovitis.
Timepoint [11] 341807 0
baseline to 12 weeks
Secondary outcome [12] 341808 0
Change in the dGEMRIC index (delayed Gadolinium Enhanced MRI of the cartilage) from baseline to week 12 in patients with clinical knee OA, significant pain and effusion-synovitis.
Timepoint [12] 341808 0
baseline to 12 weeks

Eligibility
Key inclusion criteria
1. Aged over 40 years old.
2. Men and women with significant knee pain on most days (defined as a VAS >40mm).
3. Knee effusion–synovitis on US (>=4mm thickness measure).
4. Meet American College of Rheumatology (ACR) clinical criteria for knee OA confirmed by a clinician.
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Inability to have an MRI (claustrophobia, metal in eyes or selected knee, pacemakers).
2. Severe knee OA (joint space narrowing (JSN) on X-ray of Grade 3 using the Osteoarthritis Research Society International (OARSI) atlas).
3. Unwillingness to stop taking Curcuma longa medications 2 weeks prior to randomization
4. Other forms of inflammatory arthritis (especially rheumatoid arthritis and gout).
5. Significant knee injury within the last 6 months.
6. Arthroscopy or open surgery in the index knee in the last 12 months, or planned.
7. Injections of corticosteroids (last 3 months) or hyaluronic acid (last 6 months) in the index knee.
8. Pregnancy or breastfeeding.
9. Use of any investigational drug(s) and/or devices within 30 days prior to randomisation
10. Presence of any serious medical illness that may preclude 24 week follow up.
11. Inability to provide informed consent.
12. Study Investigators consider the patient is otherwise unsuitable for the study including the assessment of kidney function for a contrast-enhanced MRI study.

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.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block 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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Statistical Analyses:
The comparisons of pain and function scores will be made using a repeated–measures mixed model with terms of treatment, time and corresponding baseline values as covariates (in addition to age, gender, BMI). The correlation within the repeated measures will be addressed by using an individual participant identification as a random effect. The effect of treatment will be evaluated by the intervention by time interaction, and then proceed to the main effects model with only group and time. Linear regression will be used to compare changes in effusion and synovitis size in univariate and multivariable modelling (if groups are not well matched at baseline) between groups. All data will be analysed using intention–to–treat principles. Per protocol analyses will be completed for study participants consuming >=80% of capsules.

Power calculations:
Sample size and power calculations were based on the primary endpoints of VAS pain score change from baseline to 12 weeks. Based on in–house data from the 4Jointz trial (SD=24), assuming 18mm difference between treatment and placebo groups on the VAS pain scale, alpha=0.05, we will need 32 participants in each group. Adjusting for 10% loss to follow–up, we need 70 participants (35 in each arm).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
25/01/2018
Actual
12/06/2018
Date of last participant enrolment
Anticipated
25/09/2018
Actual
21/12/2018
Date of last data collection
Anticipated
24/12/2018
Actual
15/03/2019
Sample size
Target
70
Accrual to date
Final
70
Recruitment in Australia
Recruitment state(s)
TAS

Funding & Sponsors
Funding source category [1] 297179 0
University
Name [1] 297179 0
Menzies Institute for Medical Research, UTAS
Country [1] 297179 0
Australia
Funding source category [2] 298357 0
Commercial sector/Industry
Name [2] 298357 0
Natural Remedies Ltd
Country [2] 298357 0
India
Primary sponsor type
University
Name
University of Tasmania
Address
Churchill Avenue,
Sandy Bay
Tasmania 7005
Country
Australia
Secondary sponsor category [1] 297481 0
None
Name [1] 297481 0
Address [1] 297481 0
Country [1] 297481 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298342 0
Tasmanian Health & Medical Human Research Ethics Committee (EC00337)
Ethics committee address [1] 298342 0
Ethics committee country [1] 298342 0
Australia
Date submitted for ethics approval [1] 298342 0
17/07/2017
Approval date [1] 298342 0
12/12/2017
Ethics approval number [1] 298342 0
H0016713

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

Contacts
Principal investigator
Name 76774 0
Dr Benny Antony
Address 76774 0
Menzies Institute for Medical Research
Private Bag 23
Hobart, TAS, 7000
Country 76774 0
Australia
Phone 76774 0
+61362264255
Fax 76774 0
Email 76774 0
[email protected]
Contact person for public queries
Name 76775 0
Gudrun Wells
Address 76775 0
Menzies Institute for Medical Research
17 Liverpool Street
Hobart, TAS, 7000
Country 76775 0
Australia
Phone 76775 0
61362266909
Fax 76775 0
61362267764
Email 76775 0
[email protected]
Contact person for scientific queries
Name 76776 0
Benny Antony
Address 76776 0
Menzies Institute for Medical Research
Private Bag 23
Hobart, TAS, 7000
Country 76776 0
Australia
Phone 76776 0
+61362264255
Fax 76776 0
Email 76776 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
we will decide on the IPD sharing agreement as soon as we publish the paper from the trial


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
EmbaseEffectiveness of curcuma longa extract for the treatment of symptoms and effusion-synovitis of knee osteoarthritis.2020https://dx.doi.org/10.7326/M20-0990
N.B. These documents automatically identified may not have been verified by the study sponsor.