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Trial registered on ANZCTR


Registration number
ACTRN12615001066572
Ethics application status
Approved
Date submitted
16/09/2015
Date registered
13/10/2015
Date last updated
19/09/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of isotretinoin on mucosal wound healing in patients with chronic sinusitis: a pilot study.
Scientific title
The effect of isotretinoin on mucosal wound healing in patients with chronic sinusitis, a pilot study by the Department of Surgery, University of Auckland.
Secondary ID [1] 287482 0
NIL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic sinusitis 296222 0
Condition category
Condition code
Inflammatory and Immune System 296495 296495 0 0
Other inflammatory or immune system disorders
Respiratory 296562 296562 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pilot RCT. 32 newly diagnosed patients with chronic sinusitis (CRS) will be recruited over 18 months. These patients will be on the waiting list for endoscopic sinus surgery, but have not yet undergone surgery.

Following informed consent to participate in the study, 2 weeks prior to surgery, a patient questionnaire to obtain subjective patient symptom scores (SNOT-22) will be performed. Swabs will be taken from the middle meatus to provide baseline data. This is a non-invasive procedure performed under endoscopic guidance, which is routinely undertaken in ORL clinics to guide appropriate antibiotic therapy for patients with sinusitis. Patients will then have topical anesthesia applied to the nasal cavity (co-phenylcaine or equivalent). A small, 3-5mm region of the antero-inferior aspect of the middle turbinate will be biopsied to create a wound.

Patients will then be allocated numbered but unmarked drug packs (double blinded) in a computer generated random sequence, to receive 2 weeks of either:

1) isotretinoin capsule 10mg once daily
2) a placebo capsule

Monitoring of medication adherence will be assessed by drug packet return.

Two weeks later, at the time of surgery, the SNOT-22 will be again performed by the patient as well as an intraoperative endoscopic healing score (Lund-Kennedy) by the surgeon. Swabs will again be taken from the middle meatus. The inferior aspect of the middle turbinate, which is often resected routinely, will be biopsied to remove both the lesion made in clinic and a small amount of the surrounding, uninjured mucosa.

Following surgery, patients will be continued on study medications (including placebo) at the same dose and frequency as the previously two weeks plus, for another two weeks. Patients will also be given any additional routine medications (usually antibiotics and steroids) as per clinical needs. Patients will be seen again at 2 weeks following surgery, at which point swabs will again be taken, along with the SNOT-5 and Lund-Kennedy scores. After this, patients will be discharged from the study and study medications (isotretinoin or placebo) stopped.
Intervention code [1] 292863 0
Treatment: Drugs
Comparator / control treatment
Data from patients receiving isotretinoin and the placebo tablet will be compared.

Placebo tablets contain microcellulose.
Control group
Placebo

Outcomes
Primary outcome [1] 296124 0
Histology
Composite outcomes - Analysis will be done for cilial recovery, collagen content, goblet cell recovery, epithelial thickness, mucosal thickness, immune cells and bacterial cells. Comparisons will be made between injured and uninjured tissue.
Timepoint [1] 296124 0
performed on sample collected at the time of surgery (2 weeks after starting study medication or placebo)
Primary outcome [2] 296177 0
Microbiology
The swabs taken before and after medical therapy will be compared. Alongside conventional culture methods, samples will also be subjected to PCR amplification of the bacterial 16S ribosomal RNA (16S rRNA) genes.
Timepoint [2] 296177 0
At times 0, 2 weeks (surgery) and 4 weeks (post op).
Primary outcome [3] 296178 0
Cytokines
Levels of important inflammatory cytokines will be measured in the mucus of the patients using a cytokine ELISA.
Timepoint [3] 296178 0
At times 0, 2 weeks (surgery) and 4 weeks (post op).
Secondary outcome [1] 317556 0
Patient reported symptom scores (Sinonasal Outcome Test –22)
Timepoint [1] 317556 0
At times 0, 2 weeks (surgery) and 4 weeks (post op).
Secondary outcome [2] 317721 0
Endoscopic scoring (Lund-Kennedy Endoscopic Score).
Timepoint [2] 317721 0
At times 0, 2 weeks (surgery) and 4 weeks (post op).
Secondary outcome [3] 318089 0
pH of mucus will be measured using a pH indicator
Timepoint [3] 318089 0
At times 0, 2 weeks (surgery) and 4 weeks (post op).

Eligibility
Key inclusion criteria
Patients newly diagnosed with CRS, are eligible for sinus surgery and on the waiting list for endoscopic sinus surgery, but not yet undergone surgery.

Patients providing fully informed consent to participate in this study.
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who are acutely unwell.
Patients with cystic fibrosis.
Patients with a history of previous nasal surgery.
Male patients less than 16 years of age
Female patients less than 45 years of age (owing to isotretinoin teratogenicity risk)
Immunodeficiency (congenital or acquired)
Congenital mucociliary problems (e.g. primary ciliary dyskinesia)
Non-invasive and invasive fungal sinus disease
Systemic vasculitis and granulomatous diseases
History of cocaine abuse;
Patients requiring sinus surgery for neoplasia
Patients unable to consent (e.g. lack of mental capacity)

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 database
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Central randomisation by computer database
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 1
Type of endpoint/s
Efficacy
Statistical methods / analysis
As the effect size for this intervention is not known, this study serves as a pilot RCT.

Analysis of variance for changes following treatment and differences of means within groups will be assessed. Alpha and beta diversity of microbial communities will be analysed. Statistical significance will be accepted at the 0.05 level.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/11/2015
Actual
23/02/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
32
Accrual to date
Final
Recruitment outside Australia
Country [1] 7170 0
New Zealand
State/province [1] 7170 0
Country [2] 7171 0
United States of America
State/province [2] 7171 0
California

Funding & Sponsors
Funding source category [1] 292058 0
Self funded/Unfunded
Name [1] 292058 0
N/A
Country [1] 292058 0
Primary sponsor type
Individual
Name
Associate Professor Richard Douglas
Address
Department of Surgery
The University of Auckland
Level 12, Room 12-087, ACH Support Building, Park Road, Grafton. 1142.
Country
New Zealand
Secondary sponsor category [1] 290729 0
Individual
Name [1] 290729 0
Dr Ravi Jain
Address [1] 290729 0
Department of Surgery
The University of Auckland
Level 12, Room 12-087, ACH Support Building, Park Road, Grafton. 1142.
Country [1] 290729 0
New Zealand
Other collaborator category [1] 278630 0
Individual
Name [1] 278630 0
Professor Peter Hwang
Address [1] 278630 0
Stanford ENT
801 Welch Rd
MC 5739
Stanford, CA94305
Country [1] 278630 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293541 0
New Zealand Northern A Health and Disability Ethics Committee
Ethics committee address [1] 293541 0
Ethics committee country [1] 293541 0
New Zealand
Date submitted for ethics approval [1] 293541 0
Approval date [1] 293541 0
07/09/2015
Ethics approval number [1] 293541 0
15/NTA/86

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

Contacts
Principal investigator
Name 60378 0
A/Prof Richard Douglas
Address 60378 0
Department of Surgery University of Auckland Private Bag 92019 Auckland Mail Centre 1142
Country 60378 0
New Zealand
Phone 60378 0
+64 27 2186083
Fax 60378 0
Email 60378 0
[email protected]
Contact person for public queries
Name 60379 0
Richard Douglas
Address 60379 0
Department of Surgery University of Auckland Private Bag 92019 Auckland Mail Centre 1142
Country 60379 0
New Zealand
Phone 60379 0
+64 27 2186083
Fax 60379 0
Email 60379 0
[email protected]
Contact person for scientific queries
Name 60380 0
Richard Douglas
Address 60380 0
Department of Surgery University of Auckland Private Bag 92019 Auckland Mail Centre 1142
Country 60380 0
New Zealand
Phone 60380 0
+64 27 2186083
Fax 60380 0
Email 60380 0
[email protected]

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

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