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Trial registered on ANZCTR


Registration number
ACTRN12617001582347
Ethics application status
Approved
Date submitted
6/11/2017
Date registered
27/11/2017
Date last updated
27/11/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Tonsil and adenoid analysis study to investigate the causes of large tonsils and adenoids in children undergoing surgical removal of the tonsils and adenoids.
Scientific title
The nature of microbial involvement in the development of adenotonsillar hyperplasia in the paediatric population.
Secondary ID [1] 293291 0
Nil known
Universal Trial Number (UTN)
U1111-1179-9697
Trial acronym
TAAS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
tonsillitis
 305364 0
adenoid hyperplasia 305365 0
tonsil hyperplasia 305366 0
Condition category
Condition code
Inflammatory and Immune System 304653 304653 0 0
Other inflammatory or immune system disorders
Respiratory 304792 304792 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Patients with a diagnosis of adenoid or tonsillar hyperplasia requiring surgery will be recruited from the Paediatric ORL Clinic at Auckland Hospital. We will then follow these patients through to surgery and gain consent for the use of a small amount of the tissue that is removed from the adenoids and the tonsils at the time of surgery and then take this tissue to the laboratory for analysis. We will look at the bacteria on the surface of the tissue and the
bacteria within the tissue to determine if there is any difference between the two. We will then aim to use these results to determine what is causing these disease processes so that our understanding of how to treat them will increase. In addition, normal control samples (nasopharyngeal and tonsillar swabs from paediatric patients having general anaesthetics for conditions not affecting the upper airways) will be obtained in order to compare our
results from patients with disease to patients without disease.
Intervention code [1] 299544 0
Diagnosis / Prognosis
Comparator / control treatment
Normal control samples (nasopharyngeal and tonsillar swabs from paediatric patients having general anaesthetics for conditions not affecting the upper airways) will be obtained in order to compare our results from patients with disease to patients without disease.
Control group
Active

Outcomes
Primary outcome [1] 303873 0
To identify the members of the adenoids microbiota in disease and healthy individuals.
Once in the laboratory the swab samples will be immediately frozen at -20oC and stored until genomic DNA is extracted. The bacterial diversity of the samples will be measured using next-generation sequencing technologies (explained in more detail below).
The first step toward describing the microbiome is to extract DNA from collected swabs or tissue. This will be conducted using a bead-beating approach that we have previously applied to sinus swab samples (Biswas et al. 2015). Extracted DNA of sufficient quantity and quality will then be subjected to PCR amplification of the bacterial 16S ribosomal RNA (16S rRNA) genes. These genes occur in all bacteria, and their analysis by sequencing or related approaches is a cornerstone of contemporary microbial ecology (Amann et al. 1995; Tringe & Hugenholtz 2008). We will employ Illumina MiSeq sequencing, one of the so-called next-generation sequencing approaches, to sequence bacterial 16S rRNA genes, using sample preparation, bioinformatics and statistics protocols that are well established in our laboratory (Webster et al. 2010; Taylor et al. 2013; Biswas et al. 2014; Schmitt et al. 2012; Simister et al. 2012). This sequencing approach yields thousands to tens of thousands of sequences per sample, enabling us to identify both the abundant and rare members of the microbiome and to survey large numbers of patients (Kuczynski et al. 2010).
Timepoint [1] 303873 0
18 months following commencement of study.
Patients with palatine tonsil hypertrophy who are undergoing adenotonsillectomy will have both their adenoid tonsils and palatine tonsils removed. These will be collected so that a comparison can be made between the microbiome of the palatine tonsils and adenoid tonsils in the same patient. Swabs will be taken from the tonsils and adenoid at the time of surgery immediately before tonsil and adenoid removal. Adenoid tonsil tissue will be removed with a curette and placed in a sterile container “fresh.” Palatine tonsils will be removed and placed in a sterile container (right and left seperate) “fresh.” These will be stored on ice and immediately collected at the end of the operation and transported to the laboratory. A 5ml blood sample from each patient involved in this study will be taken at the time of general anaesthetic when the patient is having an intravenous line sited for anaesthetic.
Secondary outcome [1] 340325 0
To investigate the 'pathogen reservoir hypothesis' with respect to adenoid- associated microbiota.
The first step toward describing the microbiome is to extract DNA from collected swabs or tissue. This will be conducted using a bead-beating approach that we have previously applied to sinus swab samples (Biswas et al. 2015). Extracted DNA of sufficient quantity and quality will then be subjected to PCR amplification of the bacterial 16S ribosomal RNA (16S rRNA) genes. These genes occur in all bacteria, and their analysis by sequencing or related approaches is a cornerstone of contemporary microbial ecology (Amann et al. 1995; Tringe & Hugenholtz 2008). We will employ Illumina MiSeq sequencing, one of the so-called next-generation sequencing approaches, to sequence bacterial 16S rRNA genes, using sample preparation, bioinformatics and statistics protocols that are well established in our laboratory (Webster et al. 2010; Taylor et al. 2013; Biswas et al. 2014; Schmitt et al. 2012; Simister et al. 2012). This sequencing approach yields thousands to tens of thousands of sequences per sample, enabling us to identify both the abundant and rare members of the microbiome and to survey large numbers of patients (Kuczynski et al. 2010).
Timepoint [1] 340325 0
18 months following study commencement.
All samples will be collected at the time of surgery while the patient is under general anaesthetic.
Secondary outcome [2] 340326 0
Examine the effect of S. aureus SAgs on T lymphocytes in adenoid tissue.
A portion of freshly excised adenoid tissue will be prepared for flow cytometry using an established method to quantify the major T and B cell subsets and assess TCR VB skewing using the IOTest® Beta Mark TCR VB Repertoire Kit (Beckman Coulter). Patient blood samples will be assessed in parallel as a comparator for systemic versus localized TCR VB skewing. Skewing will be defined as a percentage of Vß-expression >2 SD of that seen in normal blood (control values supplied with the kit), as described previously , and successfully employed in our laboratory for TCR subset analysis of tonsil tissue. Excess adenoid tissue will be preserved for assessment of bacterial diversity as outlined above, histology, localization of bacteria by fluorescent in situ hybridisation (FISH) and cultivation of bacteria.
Timepoint [2] 340326 0
24 months following study commencement.
All samples will be collected at the time of surgery while the patient is under general anaesthetic.

Eligibility
Key inclusion criteria
Age between 3 and 16 years.
Undergoing otolaryngology surgery for non-infectious pathology.
Patients selected following study participant recruitment to represent age, ethnicity, and gender of participant population group.
Minimum age
3 Years
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with genetic syndromes, metabolic disorders, neurologic diseases or congenital malformations will be excluded.
Patients with anatomical abnormality of the upper aerodigestive tract.
Patients who have had antibiotics within the 2 weeks prior to surgery.
Previous adenoidectomy, tonsillectomy, or grommet insertion.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
One hundred patients with a diagnosis of adenotonsillar hyperplasia will be recruited from the Paediatric ORL Clinic at Auckland Hospital. In addition twenty five normal control samples (nasopharyngeal swabs from paediatric patients having general anaesthetics for conditions not affecting the upper airways) will be obtained.Blood samples will also be taken from both groups of patients for analysis. The first step toward describing the microbiome is to extract DNA from collected swabs and tissue.

After meeting with a biostatistician we calculated that power was sufficient to test for a difference of a binary outcome between 2 groups, 100 in study group, 25 in controls, there would be 80% power to detect a difference at the 5% level of significance if the real occurrence is approximately 30% more in the study group compared to controls (controls 5%, study group 29%, controls 20% study 50%, controls 50% study 79%) Increasing the controls
to 50 only changes the study group values to 22%, 43% and 73% respectively. As we are focusing on a large difference between control and study group we calculate that 25 patients in the control group is enough detect clinical significance.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
5/06/2017
Date of last participant enrolment
Anticipated
14/05/2018
Actual
Date of last data collection
Anticipated
14/05/2018
Actual
Sample size
Target
125
Accrual to date
30
Final
Recruitment outside Australia
Country [1] 9335 0
New Zealand
State/province [1] 9335 0
Auckland

Funding & Sponsors
Funding source category [1] 297915 0
University
Name [1] 297915 0
The University of Auckland
Country [1] 297915 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
Research Office
University of Auckland
Private Bag 92019
Auckland Mail Centre
1142
Country
New Zealand
Secondary sponsor category [1] 296978 0
None
Name [1] 296978 0
Address [1] 296978 0
Country [1] 296978 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298965 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 298965 0
Ethics committee country [1] 298965 0
New Zealand
Date submitted for ethics approval [1] 298965 0
28/04/2016
Approval date [1] 298965 0
24/05/2016
Ethics approval number [1] 298965 0
16/STH/53

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2175 2175 0 0
/AnzctrAttachments/373940-TAAS Study Protocol_3 June 2016.docx (Protocol)
Attachments [2] 2176 2176 0 0
/AnzctrAttachments/373940-TAAS Parent Legal Gaurdian Information Sheet and Consent From_Version 3.docx (Participant information/consent)
Attachments [3] 2177 2177 0 0
/AnzctrAttachments/373940-TAAS Control Parent Legal Gaurdian Information Sheet and Consent From_Version 3.docx (Participant information/consent)
Attachments [4] 2178 2178 0 0
/AnzctrAttachments/373940-HDEC Letter 16STH53 Approved FULL Application with NSC.pdf (Ethics approval)

Contacts
Principal investigator
Name 78818 0
Dr James Johnston
Address 78818 0
Department of Surgery
University of Auckland
Private Bag 92019
Auckland Mail Centre 1142
Country 78818 0
New Zealand
Phone 78818 0
+64211716814
Fax 78818 0
Email 78818 0
jj.johnston@auckland.ac.nz
Contact person for public queries
Name 78819 0
James Johnston
Address 78819 0
Department of Surgery
University of Auckland
Private Bag 92019
Auckland Mail Centre 1142
Country 78819 0
New Zealand
Phone 78819 0
+64211716814
Fax 78819 0
Email 78819 0
jj.johnston@auckland.ac.nz
Contact person for scientific queries
Name 78820 0
James Johnston
Address 78820 0
Department of Surgery
University of Auckland
Private Bag 92019
Auckland Mail Centre 1142
Country 78820 0
New Zealand
Phone 78820 0
+64211716814
Fax 78820 0
Email 78820 0
jj.johnston@auckland.ac.nz

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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