Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000259640
Ethics application status
Approved
Date submitted
27/02/2014
Date registered
11/03/2014
Date last updated
5/02/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase II, randomized, double-blind, placebo-controlled dose ranging pilot study investigating the efficacy and safety of supplementation with Arthrem in patients with hip and knee osteoarthritis
Scientific title
A phase II, randomized, double-blind, placebo-controlled dose ranging pilot study investigating the efficacy and safety of supplementation with Arthrem, an extract of Artemisia annua, in improving symptoms of hip and knee osteoarthritis
Secondary ID [1] 283988 0
None
Universal Trial Number (UTN)
U1111-1150-7414
Trial acronym
ARTH01
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis of the hip or knee 291018 0
Condition category
Condition code
Alternative and Complementary Medicine 291361 291361 0 0
Herbal remedies
Musculoskeletal 291362 291362 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Two active treatment groups will receive the dietary supplement Arthrem, an extract of the medicinal plant Artemisia annua. Subjects will receive one capsule (orally) twice daily in either 17 mg Arthrem group (total daily dose 34 mg) or the 34 mg Arthrem group (total daily dose 68 mg).
Compliance will be assessed by patient medication diaries and also by the return of unused capsules at each visit.
Duration: 12 weeks
There will be an optional, open-label, long term safety follow up study. Subjects choosing to take part will receive 1x 17 mg capsule twice daily (total daily dose 34 mg) for up to 6 months after the double-blind 12 week study.
Intervention code [1] 288674 0
Treatment: Other
Comparator / control treatment
Subjects in the placebo group will receive two placebo capsules (orally) twice daily. The placebo capsules consist of an identical capsule to the active capsule but contain only vegetable oil.
Control group
Placebo

Outcomes
Primary outcome [1] 291357 0
The Western Ontario and McMaster Universities (WOMAC) index assesses pain, stiffness and functionality in patients with osteoarthritis.
Timepoint [1] 291357 0
0, 6, 12 weeks
Secondary outcome [1] 306586 0
Safety: adverse events, laboratory safety tests (full blood count, liver function tests, urea and electrolytes, C-reactive protein), vital signs, physical examination.
Adverse events will be collected and monitored throughout the study. Artemisia annua has not been previously tested in osteoarthritis, but from previous trials in other indications, it is anticipated that the most common adverse events will be gastrointestinal in nature (eg nausea).
Vital signs and laboratory safety tests will be measured at each study visit. Results will be classified by the principal investigator as normal, abnormal but not clinically significant, or abnormal and clinically significant. Parameters that are considered to be abnormal and clinically significant will be reported as adverse events.
Timepoint [1] 306586 0
0, 6, 12 weeks (and throughout the study for adverse events)
Secondary outcome [2] 306587 0
The Health Assessment Questionnaire (HAQ) assesses patients' abilities with sections on dressing, rising, eating, walking, hygiene, reach, grip and activities.
Timepoint [2] 306587 0
0, 6, 12 weeks
Secondary outcome [3] 306588 0
Visual analogue pain scale (VAS)
Timepoint [3] 306588 0
0, 6, 12 weeks

Eligibility
Key inclusion criteria
- Pain from either or both knees and/or hips on most days of the previous 3 months combined with definite radiological changes of osteoarthritis
- Stable dose of current regular medication for at least 4 weeks prior to study entry
- A minimum score on a pre-screening visual analogue pain scale of at least 30 mm on a 100 mm scale averaged over the last 7 days
Minimum age
35 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pregnancy/breastfeeding
- Significant renal or hepatic impairment
- Hip or knee surgery within past 6 months
- Current or recent (in the last 3 months) oral or intra-articular corticosteroid therapy;
- Co-morbid inflammatory arthritis such as rheumatoid arthritis
- History of hip or knee joint replacement or osteotomy at index joint
- Other previous hip or knee pathology such as a recent fracture (<3 months) or malignancy
- Significant illness other than osteoarthritis
- Taking any form of herbal/multivitamin/nutritional supplements for osteoarthritis (i.e. glucosamine, fish oil, green-lipped mussel) within 3 weeks
- Participation in another research study involving an investigational product in the past 12 weeks

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)
Participants will be recruited from the hospital records and also from newspaper and radio advertisements.
Participants will be randomised to one of three treatment groups: (1) Arthrem 17 mg twice daily, (2) Arthrem 34 mg twice daily, or (3) placebo twice daily.

Potential participants will be invited to telephone the clinical trial nurse who will assess their initial eligibility. Eligibility will be confirmed at a screening visit.

Participants will be given sequential patient numbers, which will correspond to one of three treatments according to a computer-generated randomisation schedule. The study treatments will be pre-labelled with the participants' study numbers according to the randomisation schedule. Neither the patients nor the person dispensing the treatment will be able to see which treatment the participant will be allocated to.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer-generated block randomisation schedule will be created by an independent scientist not otherwise associated with 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
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The primary endpoint is the change from baseline in overall WOMAC score at Week 12.
Summaries and change from baseline in overall WOMAC score at each time point will be presented using descriptive statistics by treatment group; these will include mean, standard deviation, median, minimum and maximum. The change from baseline to Week 12 will be analysed using a linear mixed model with dose as a fixed effect and subject as a random effect. The change from baseline for each treatment group will be compared to zero and a 95% confidence interval for the change will be presented.
The secondary endpoints include the change from baseline in HAQ and VAS pain score at Week 12 and the change from baseline in WOMAC pain score at Week 12; these will be summarized using the same method employed for the primary endpoint.
There are currently no suitable data available that allow a persuasive sample size calculation for the effects of the effects of Arthrem in osteoarthritis. Due to this limitation the study is considered as a pilot, proof of concept study. The sample size is based on the between patient variation in WOMAC overall score previously observed in OA patients and assuming a mean of 38.0 and a standard deviation of 18.0.
A total of 42 participants will be treated with the investigational product. This study will have approximately 80% power to detect a 20% reduction in overall WOMAC score with a significance level of 5%. Thirteen participants per group are needed to provide an 80% power in this pilot study. To allow for a 5% drop-out (attrition rate) 14 participants will be enrolled in each of the three treatment groups (low dose, high dose and placebo) in a 1:1:1 ratio (42 participants overall). The type I error (alpha level) has been set at 0.05 for subjects.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/04/2014
Actual
28/05/2014
Date of last participant enrolment
Anticipated
Actual
17/11/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
42
Accrual to date
Final
42
Recruitment outside Australia
Country [1] 5779 0
New Zealand
State/province [1] 5779 0
Dunedin

Funding & Sponsors
Funding source category [1] 288614 0
Commercial sector/Industry
Name [1] 288614 0
Promisia Ltd
Country [1] 288614 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Promisia Ltd
Address
Level 15, 171 Featherston Street
Wellington 6011
Country
New Zealand
Secondary sponsor category [1] 287322 0
None
Name [1] 287322 0
Address [1] 287322 0
Country [1] 287322 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290474 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 290474 0
Ethics committee country [1] 290474 0
New Zealand
Date submitted for ethics approval [1] 290474 0
23/01/2014
Approval date [1] 290474 0
26/02/2014
Ethics approval number [1] 290474 0
14/NTB/11

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

Contacts
Principal investigator
Name 45814 0
Dr Simon Stebbings
Address 45814 0
Rheumatology Research Unit
Department of Medicine
Dunedin School of Medicine
University of Otago
PO Box 913
Dunedin 9054
Country 45814 0
New Zealand
Phone 45814 0
+64 3 474 0999
Fax 45814 0
Email 45814 0
simon.stebbings@otago.ac.nz
Contact person for public queries
Name 45815 0
Sheena Hunt
Address 45815 0
Promisia Ltd
Level 15, 171 featherston Street
Wellington 6011
Country 45815 0
New Zealand
Phone 45815 0
+64 4 894 8524
Fax 45815 0
Email 45815 0
sheena@promisia.com
Contact person for scientific queries
Name 45816 0
Sheena Hunt
Address 45816 0
Promisia Ltd
Level 15, 171 featherston Street
Wellington 6011
Country 45816 0
New Zealand
Phone 45816 0
+64 4 894 8524
Fax 45816 0
Email 45816 0
sheena@promisia.com

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
EmbaseA pilot randomized, placebo-controlled clinical trial to investigate the efficacy and safety of an extract of Artemisia annua administered over 12 weeks, for managing pain, stiffness, and functional limitation associated with osteoarthritis of the hip and knee.2016https://dx.doi.org/10.1007/s10067-015-3110-z
EmbaseAn open-label six-month extension study to investigate the safety and efficacy of an extract of artemisia annua for managing pain, stiffness and functional limitation associated with osteoarthritis of the hip and knee.2016
N.B. These documents automatically identified may not have been verified by the study sponsor.