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Trial registered on ANZCTR


Registration number
ACTRN12616000022460
Ethics application status
Approved
Date submitted
8/01/2016
Date registered
14/01/2016
Date last updated
9/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Probiotic for Eczema Treatment
Scientific title
Safety testing of the probiotic, M. luteus Q24 for eczema treatment
Secondary ID [1] 288260 0
Nil known
Universal Trial Number (UTN)
U1111-1177-1288
Trial acronym
PET
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Eczema 297208 0
Condition category
Condition code
Skin 297416 297416 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Micrococcus luteus Q24 will be cultured to achieve a concentration of 10^7-8 cfu/gram. The Q24 cells will be killed so only the metabolites remain and then formulated as an ointment using a Cetomacrogol base, a peony perfume and carotene for colour.. There will be a 5% concentration of the killed bacteria in the final ointment. The actual volume used will depend on the extent of the eczema and the size of the body . Initially active, placebo and Cetomacrogol ointment will each be applied as open tests to healthy unaffected skin on vertical sites (3 square cm) of the mid-upper back of each individual participant.. Skin reactions will be monitored every 15 minutes for 1 hour by the study investigator. If there are no reactions to the open test, the active, placebo, Cetomacrogol ointments and a saline control will be applied to a different site of healthy skin on one side of the spine using patch tests. Patches will be removed after 48 hours by the participant and read 72 hours later by study investigator. Providing there are no adverse reactions following the open and patch tests on healthy skin, the study investigator will test the ointment that the participant will be randomised to on eczematous skin of each individual. The participant will be observed by the study investigator for 1 hour following the application to eczematous skin. If there are no adverse reactions, participants will be provided with the appropriate ointment to apply thinly each day on all eczema sites on their body and one non-eczema skin site for a period of 4 weeks. There are no washout periods between the different tests, as each test is to be conducted in a different location of the body.

Participants will be asked to keep a daily record of their use of the study ointment.
Intervention code [1] 293552 0
Treatment: Other
Comparator / control treatment
The placebo preparation will contain the Cetomacrogol base, the peonie perfume and carotene for colour, as used in the active intervention. The latter is so that both active and placebo appear a similar colour.
Control group
Placebo

Outcomes
Primary outcome [1] 296977 0
To assess safety, differences between active and placebo ointment in skin reactions after 1 hour, including area involved, erythema (area involvement and strength), papules and vesicles will be assessed using the standard scale for repeated open application tests (ROAT). The ROAT scale of evaluation was developed by Johansen JD et al (Contact Dermatitis 1997:39:95) to evaluate repeated applications of the test substance. We are using a modified version of this test where the test substances are applied only once but have adopted this ROAT scale for reading the test results. As far as I am aware the test has not been validated.
Timepoint [1] 296977 0
The open test is to be assessed every 15 mintue till 1 hour after application of the ointments
Primary outcome [2] 299635 0
Assuming there is no reaction to the open test, a patch test to the active and placebo ointments will be applied, A reaction will be measured using a standard patch test protocol with grades ranging from no reaction, doubtful reaction, weak positive reaction, strong positive reaction and extreme positive reaction. Each of these grades are determined by the amount of erythema, infiltration, papules and vesicles.
Timepoint [2] 299635 0
Patches are removed from the skin after 48 hours and read after 72 hours,
Primary outcome [3] 299636 0
Assuming no reaction to the patch test, tolerance to the study ointment that the participant is randomized to when placed on eczematous skin will be measured using the intensity criteria from the internationally standardised Eczema Area and Severity Index (EASI). These include erythema, oedema/papulation, excoriation and lichenification. The severity of each is scored on a scale of 0-3.
Timepoint [3] 299636 0
Every 15 minutes until 1 hour after application of ointment to eczematous skin.
Secondary outcome [1] 319790 0
To assess efficacy, differences between study groups in Eczema Area and Severity Index (EASI) using this standard international measure of eczema severity.
Timepoint [1] 319790 0
At baseline and after 4 weeks of daily application of ointment
Secondary outcome [2] 319791 0
Using skin swabs from one non-eczematous site and from the most severe eczema site at baseline and at the end of treatment, differences in skin microbiota between eczematous and non-eczematous sites and between study ointments will be measured using 16sRNA DNA sequencing. If the most severe site at the end of the study is different from the most severe site at baseline, a skin swab will also be taken from this site.
Timepoint [2] 319791 0
After 4 weeks of daily use
Secondary outcome [3] 319883 0
Ease of use of study ointments will be assessed by questionnaire
Timepoint [3] 319883 0
After 4 weeks
Secondary outcome [4] 319884 0
Acceptability of study ointments will be assessed by questionnaire
Timepoint [4] 319884 0
After 4 weeks
Secondary outcome [5] 319885 0
Self reported eczema severity measured by the standard Patient Orientated Eczema Measure (POEM) questionnaire.
Timepoint [5] 319885 0
POEM questionnaire to be completed at baseline and weekly for 4 weeks

Eligibility
Key inclusion criteria
Eligible participants will:
1. be adults (age >15-60)
2. with visible eczema according to the UK criteria and
3. an Eczema Area and Severity Index (EASI) value >=2 to exclude minor eczema or <=50 to exclude those with very severe eczema whose symptoms may worsen if their treatment regime changes.
Minimum age
16 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Non-English speaking
2. Pregnant or planning to become pregnant
3. Use in the last 6 months of oral steroids
4. *Use in the last 14 days of topical or systemic antibiotics applied to eczema
5. Continuous use of systemic antibiotics over past 3 months
6 *Use of wet wraps in the last 14 days
7. A severe systemic disorder e.g. renal failure, heart disease, cystic fibrosis, immunodeficiency, muscular dystrophy or cancer where in the opinion of the investigator participation is inappropriate.
8. *Use of immune suppressants such as cyclosporine, methotrexate, mycophenolate and azathioprine in the last 30 days.
9. *Use of pimecrolimus (Elidel), tacrolimus (Protopic) or ultraviolet treatment in the last 14 days.
10. **Current or planned use of probiotic supplements, applications or drinks
11. Moving from study centre during 6 weeks of study duration
12. Refusal of permission to contact health carers
13. Any other reason that deems the participant inappropriate for study
14. Has contact dermatitis only (symptoms present on hands only)
15. Has a known intolerance to Cetomacrogol, as this is the ointment used as a base in both the active and placebo arms of the trial.
16. Has past reaction to soya or dairy foods and avoids eating either of these.

*Recruitment may occur at a later date if these treatments can be avoided for the specified time.
**Recruitment may occur if probiotics are stopped for 2 weeks and a commitment is made not to recommence them for the study duration

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 will be concealed by use of allocation schedules developed by a statistician who will not be involved in study assessments. The numbers on the schedules will correspond to numbers (for efficacy randomisation) or letters (for safety open and patch skin tests) on the pots of ointment..
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
There are two stages of the study. For each stage, randomisation schedules will be prepared by a statistician using computerized sequence generation.
1. Safety testing of the product. There are 2 different tests at this stage - the open and the patch test. For each eligible participant undergoing the open test, the active, placebo or Cetomacrogol ointment will be randomly assigned using computerized sequence generation to an upper, mid of lower position on one side of the participant’s mid to upper spine so the ointments are not visible to the participant. Then, for each participant undergoing the patch test, the active, placebo and Cetomacrogol ointments and saline control will be randomly assigned using computerized sequence generation to one of four wells within the patch test. For each test, the researcher applying the ointment will be different from the researcher who is assessing the skin at the end of the test. All participants, will also undergo a two week run-in period during which they use Cetomacrogol moisturizer daily.

2. Efficacy All participants who demonstrate tolerance to the study ointments during the safety testing and the Cetomacrogol during the run-in period will be given a study number and randomly assigned using computerized sequence generation to the active (n=20) or placebo (n=20) arm of the study.
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
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
A phase 1 trial is not expected to be powered to show statistically significant differences in adverse events that may be attributable to an intervention. Nevertheless indications of any safety concerns will be assessed by describing and comparing the degree of severity of any skin reactions between study groups using Wilcoxon signed-rank tests. Positive and negative comments by participants will be coded and their frequency investigated by study group. The biological plausibility of any significant or large differences between study groups will be assessed by a physician. The trial is also not powered to examine efficacy of the study probiotic, which is a secondary outcome. Rather, mean (SD) EASI (Eczema Area and Severity Index) will be compared between groups and used to inform a power calculation for a larger future study.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Safety concerns
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 outside Australia
Country [1] 7502 0
New Zealand
State/province [1] 7502 0
Wellington

Funding & Sponsors
Funding source category [1] 292645 0
University
Name [1] 292645 0
University of Otago
Address [1] 292645 0
P O Box 7343
Wellington South
Wellington 6021
Country [1] 292645 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
P O Box 7343
Wellington South
Wellington 6021
Country
New Zealand
Secondary sponsor category [1] 291361 0
None
Name [1] 291361 0
None
Address [1] 291361 0
None
Country [1] 291361 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294121 0
Health and Disability Ethics Committee
Ethics committee address [1] 294121 0
Ministry of Health
P O Box 5013
Wellington 6011
Ethics committee country [1] 294121 0
New Zealand
Date submitted for ethics approval [1] 294121 0
02/12/2015
Approval date [1] 294121 0
04/02/2016
Ethics approval number [1] 294121 0
15/NTA/213

Summary
Brief summary
Eczema is a major problem among New Zealand children, particularly among Maori and Pacific peoples where infected eczema is a leading cause of hospitalization. We plan to safety test a lysate of Micrococcus luteus Q24 as an eczema treatment. This lysate is from a bacterium that naturally occurs on the skin. There is evidence that it has both anti-inflammatory and antibacterial properties and thus offers a natural alternative to topical steroids and antibiotics, important given the well-recognized global problem of antibiotic resistance. This will pave the way for a larger test of efficacy and a new way of managing eczema.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62550 0
Dr Kristin Wickens
Address 62550 0
P O Box 7343
Wellington South
Wellington 6021
Country 62550 0
New Zealand
Phone 62550 0
+64 4 918 6780
Fax 62550 0
+64 4 385 5489
Email 62550 0
kristin.wickens@otago.ac.nz
Contact person for public queries
Name 62551 0
Dr Kristin Wickens
Address 62551 0
P O Box 7343
Wellington South
Wellington 6021
Country 62551 0
New Zealand
Phone 62551 0
+64 4 918 6780
Fax 62551 0
+64 4 385 5489
Email 62551 0
kristin.wickens@otago.ac.nz
Contact person for scientific queries
Name 62552 0
Dr Kristin Wickens
Address 62552 0
P O Box 7343
Wellington South
Wellington 6021
Country 62552 0
New Zealand
Phone 62552 0
+64 4 918 6780
Fax 62552 0
+64 4 385 5489
Email 62552 0
kristin.wickens@otago.ac.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary