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Trial registered on ANZCTR


Registration number
ACTRN12618000342213
Ethics application status
Approved
Date submitted
28/02/2018
Date registered
6/03/2018
Date last updated
6/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A series of N-of-1 trials to assess the efficacy of a probiotic supplement in pain associated with osteoarthritis
Scientific title
A series of N-of-1 trials to assess the efficacy of a probiotic supplement in pain associated with osteoarthritis
Secondary ID [1] 294161 0
Nil
Universal Trial Number (UTN)
U1111-1209-8994
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
osteoarthritis 306793 0
Condition category
Condition code
Musculoskeletal 305896 305896 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
One 600mg probiotic capsule containing Lactobacillus rhamnosus (LGG®) (10 x 109CFU) Saccharomyces cerevisiae (boulardii) (7.5 x 109 CFU) and Bifidobacterium animalis ssp lactis (BB-12®) (5 x 109 CFU) will be administered orally twice daily for 3 treatment intervals of 3 weeks each.

Each treatment interval will be matched with a 3-week placebo interval, separated by a 2-week washout between intervals.

Compliance with both the active and placebo intervals with be assessed by counting the unused capsules which are returned at each clinical visit.

Rescue medication is paracetamol. The usage of paracetamol will be self-reported and recorded at each clinical visit. Paracetamol (500mg tablets) usage is recommended at a maximum dosage of 8 tablets per day at the participant's discretion.
Intervention code [1] 300453 0
Treatment: Other
Comparator / control treatment
Placebo consisting of identical capsules containing microcrystalline cellulose
Control group
Placebo

Outcomes
Primary outcome [1] 304936 0
Pain reduction using 100mm VAS
Timepoint [1] 304936 0
21 days post-commencement of intervention.
Secondary outcome [1] 343651 0
Patient Specific Functional Scale (PSFS) consisting of up to five self-nominated items that the participant perceives to most interfere with their daily functioning. The participant rates each item on a numerical scale 0 to 10 where 0 represents “no difficulties” and 10 represents “can’t do it at all”.
Timepoint [1] 343651 0
This scale will be completed at the beginning and end of each 3-week intervention period.
Secondary outcome [2] 343652 0
2005-Complete Digestive Stool Analysis (CDSA) kit to assess the micro-organism concentration: Lactobacillus rhamnosus (LGG); Bifidobacterium animalis ssp lactis (BB-12); Saccharomyces cerevisiae (boulardii)
Timepoint [2] 343652 0
Participants will collect stool samples using a NutriPATH CDSA Stool Kit on four occasions. Data collection will be recorded at beginning and end of treatment periods 1 & 2 i.e. Weeks 2, 5, 7 and 10.
Secondary outcome [3] 343653 0
Rescue medication usage. Paracetamol (500mg tablets) is the preferred rescue medication. This will be used at participant's discretion. Data in relation to usage will be sought and recorded by the naturopath at every clinical visit, i.e. Weeks 2, 5, 7, 10, 12, 15, 17, 20, 22, 25, 27, 30.
Timepoint [3] 343653 0
Paracetamol usage will be monitored throughout the 30 weeks of the trial duration. Data will be recorded at the beginning of each treatment and washout period i.e. Weeks 2, 5, 7, 10, 12, 15, 17, 20, 22, 25, 27, 30.
Secondary outcome [4] 344046 0
2005-Complete Digestive Stool Analysis (CDSA) kit to assess the metabolic markers: Short Chain fatty acids (SCFAs); butyrate; ß-Glucuronidase; pH; acetate; Propionate
Timepoint [4] 344046 0
Participants will collect stool samples using a NutriPATH CDSA Stool Kit on four occasions. Data collection will be recorded at beginning and end of treatment periods 1 & 2 i.e. Weeks 2, 5, 7 and 10.
Secondary outcome [5] 344047 0
2005-Complete Digestive Stool Analysis (CDSA) kit to assess the Inflammatory markers: Transglutaminase IgA; Eosinophil Protein X; Calprotectin
Timepoint [5] 344047 0
Participants will collect stool samples using a NutriPATH CDSA Stool Kit on four occasions. Data collection will be recorded at beginning and end of treatment periods 1 & 2 i.e. Weeks 2, 5, 7 and 10.

Eligibility
Key inclusion criteria
• Females and males, aged between 18 and 85 years
• Medical diagnosis and clinical evidence of osteoarthritis in any site
• In good general health
• Female participants of childbearing age who agree to continue using birth control measures for the duration of the study

Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• A history of trauma associated with the affected joint
• Rheumatoid arthritis or other inflammatory joint conditions
• Recent history gout
• Individuals with a chronic GIT condition, including diarrhoeic conditions
• Individuals with diabetes
• Individuals with a compromised immune system
• Individuals taking antidepressants with medication not stable for 6 months
• Individuals taking Warfarin or other anti-coagulant medication
• Use of corticosteroids (intra-articular or systematic) within 4 weeks prior to baseline and throughout the study
• Female participants who are lactating, pregnant or planning to become pregnant
• Participants who have participated in another clinical trial in the last 30 days
• Participants unwilling to comply with the study protocol
• Any other condition, which in the opinion of the investigators could compromise the 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)
Randomisation code will be generated by an individual not associated with the study personnel.
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
The people analysing the results/data
Intervention assignment
Other
Other design features
The N-of-1 design, a subgroup of the randomized control trial (RCT) methodology is an experimental design involving a single participant who is exposed and withdrawn from the active intervention during multiple periods over time. It resembles a cross-over RCT, since the participant is their own control, being alternately and successively exposed to the intervention and the comparator. This alternating exposure of both periods is called a block or pair, and must occur at least twice but three or more blocks are preferable. The sequence of the periods within a block is determined by a random process. This study will consist of three 3-week active treatment intervals matched with three 3-week placebo intervals. Each interval will be separated by a 2-week washout period.
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary method of analysing the data will be by systematic visual graphing of the pain scale over the exposure/placebo conditions. This is the method recommended by the CONSORT collaboration, extension for N-of-1 studies (CENT) (Shamseer et al., 2016). In keeping with the advice from CENT, this descriptive, graphic approach will be augmented with appropriate descriptive statistics and hypothesis testing using paired t-tests of aggregated means where appropriate. The primary research question is whether pain is reduced for the patient, which will be evident from the patient’s reports on which condition worked best and reinforced by the visual graph. As we are also conducting a series of N-of-1 trials, the results of all the trials will be aggregated to form a secondary analysis that may help to obtain generalisable, population estimates.

Recruitment
Recruitment status
Not yet 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)
NSW
Recruitment postcode(s) [1] 21754 0
2106 - Newport
Recruitment postcode(s) [2] 21755 0
2147 - Kings Langley

Funding & Sponsors
Funding source category [1] 298797 0
Commercial sector/Industry
Name [1] 298797 0
Australian Traditional Medicine Society
Address [1] 298797 0
12/27 Bank St, Meadowbank NSW 2114
Country [1] 298797 0
Australia
Primary sponsor type
Individual
Name
Assoc Professor Sandra Grace
Address
School of Health and Human Sciences,
Southern Cross University
Military Rd,
Lismore NSW 2480
Country
Australia
Secondary sponsor category [1] 297985 0
Commercial sector/Industry
Name [1] 297985 0
Metagenics Inc
Address [1] 297985 0
Health World Limited
741 Nudgee Road
Northgate, Queensland 4013
Country [1] 297985 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299743 0
Southern Cross University Human Research Ethics Committee
Ethics committee address [1] 299743 0
Southern Cross University
Military Rd,
Lismore NSW 2480
Ethics committee country [1] 299743 0
Australia
Date submitted for ethics approval [1] 299743 0
18/12/2017
Approval date [1] 299743 0
28/02/2018
Ethics approval number [1] 299743 0
ECN-18-001

Summary
Brief summary
Osteoarthritis (OA) is degenerative disease effecting joints and is characterized by articular cartilage remodeling. It is one of the most common musculoskeletal disorders worldwide and affects an estimated 15% of Australians (3 million people) (Glyn-Jones et al., 2015). OA causes pain and eventual disability, and while not usually considered an inflammatory condition, there is associated inflammation of synovial tissue (Benito et al., 2005). The complex nature of the symbiotic relationship between the gastrointestinal microflora or microbiome and the health of the host has been elucidated in recent years. An unbalanced microbiome, dominated by certain species increases the risk of diverse systemic diseases, and inflammation, often low grade and chronic, is a common factor in many of these conditions. Evidence from animal and human trials suggest probiotics may be able to positively impact bone metabolism, reduce inflammation and pain attenuating inflammation via improving muscosal barrier health (Collins et al, 2015, Lei et al., 2014)) (Lei, 2014). The project aims to assess whether a three week course of probiotics is effective for reducing the pain associated with osteoarthritis in two participants diagnosed with osteoarthritis.This is an N-of-1 series, consisting of two double-blind placebo-controlled N-of-1 trials in otherwise healthy individuals. Each trial incorporates 3 randomised blocks, each consisting of 2 X 3-week period, which may comprise either the active or placebo supplement, designated A or B . Between each period there is a 2-week washout period. The primary outcome is self-reported pain, as measured by a 100mm Visual Analogue Scale. Secondary outcomes include the Patient Specific Functional Scale (PSFS) which consists of up to five self-nominated items that the participant perceives to most interfere with their daily functioning. The participant rates each item on a numerical scale 0 to 10 where 0 represents “no difficulties” and 10 represents “can’t do it at all”. This scale will be completed at the beginning and end of each 3-week intervention period. Usage of the preferred rescue medication (paracetamol) will be monitored throughout the 30-week duration of the study. The 2005-Complete Digestive Stool Analysis (CDSA) kit will be used to monitor the probiotic concentration on four occasions (Weeks 2, 5, 7 and 10).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81430 0
A/Prof Sandra Grace
Address 81430 0
Director of Research School of Health & Human Sciences Southern Cross University PO Box 157, Lismore NSW 2480
Country 81430 0
Australia
Phone 81430 0
+61 2 6620 3648
Fax 81430 0
Email 81430 0
sandra.grace@scu.edu.au
Contact person for public queries
Name 81431 0
A/Prof Sandra Grace
Address 81431 0
Director of Research School of Health & Human Sciences Southern Cross University PO Box 157, Lismore NSW 2480
Country 81431 0
Australia
Phone 81431 0
+61 2 6620 3646
Fax 81431 0
Email 81431 0
sandra.grace@scu.edu.au
Contact person for scientific queries
Name 81432 0
A/Prof Sandra Grace
Address 81432 0
Director of Research School of Health & Human Sciences Southern Cross University PO Box 157, Lismore NSW 2480
Country 81432 0
Australia
Phone 81432 0
+61 2 6620 3646
Fax 81432 0
Email 81432 0
sandra.grace@scu.edu.au

No information has been provided regarding IPD availability
Summary results
No Results