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Trial registered on ANZCTR


Registration number
ACTRN12617000207314
Ethics application status
Approved
Date submitted
3/02/2017
Date registered
8/02/2017
Date last updated
25/11/2019
Date data sharing statement initially provided
19/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
“Quercetin as an augmentation agent in Treatment Resistant Schizophrenia”
Scientific title
“Quercetin as an augmentation agent in Treatment Resistant Schizophrenia”
Secondary ID [1] 291066 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
schizophrenia 301863 0
Condition category
Condition code
Mental Health 301543 301543 0 0
Schizophrenia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Addition of quercetin (600mg) bromelain (200mg) tablets (Quercetain) to current medication regimen in a placebo controlled double blind crossover trial.
Investigational product: Quercetain
Dose: 30mg/kg rounded to nearest whole capsule divided into 2 doses given morning and night. Quercetain is given twice a day for 60 days.
There is no washout period
Quercetain is added to the patient's existing regiment without any changes to the existing medications. All patients are inpatients and are administered their medications by nursing staff as normal ward procedure. Adherence will be monitored by the ward clinical pharmacist by chart review.
Total duration: 120 days
Crossover at 60 days
Intervention code [1] 297052 0
Treatment: Other
Comparator / control treatment
The control group is the placebo arm. Both the active and placebo will consist of overencapsulated tablets. The placebo tablets will consist of Avicel (microcrystalline cellulose tablets)
Control group
Placebo

Outcomes
Primary outcome [1] 300941 0
Proportion of participants with a reduction in PANSS of 20% or greater.
Timepoint [1] 300941 0
60 days of active treatment
Secondary outcome [1] 331249 0
Proportion of participants with a 25% or greater inprovement on NOSIE.
Timepoint [1] 331249 0
60 days of active treatment
Secondary outcome [2] 331250 0
Proportion of participants with 25% or greater increase in Functional health, as measured by change in scores on the Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form
Timepoint [2] 331250 0
60 days of active treatment
Secondary outcome [3] 331251 0
Proportion of participants with 25% or greater improvement on Self-assessment of side effects of medications as measured by the “My Medicines & Me Questionnaire (M3Q)
Timepoint [3] 331251 0
60 days of active treatment

Eligibility
Key inclusion criteria
Primary diagnosis of schizophrenia
Treatment resistant schizophrenia
Absence of centrally mediated side effects e.g. sedation, EPSE
Stable medications for 2 months
Minimum age
18 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Allergy to Quercetin or Quercetain (Registered Trademark)
Pregnancy or lactation
ongoing alcohol and substance abuse, brain damage or severe comorbid medical conditions that is likely to affect the CNS
Failure to respond to antipsychotic treatment because of non-adherence to treatment or intolerable side effects
Presence of a serious medical condition as defined as a disease that is likely to require an unplanned hospital admission for treatment in the period of the trial.
Use of medications which are likely to interact significantly with quercetin including: Digoxin, Verapamil, Cyclosporin, Topotecan, Quinidine, Raitanovir, Methotrexate, Dabigatran, Rivaroxaban. The Principal Investigator will evaluate the potential for interactions between quercetin and medications in the participant’s regimen.

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 involved contacting the holder of the allocation schedule (the clinical trials pharmacist) who was at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
a randomised number system generated by the statistical randomiser, “Research Randomizer” will be used to determine whether participants receive quercetin or placebo treatment
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
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Anecdotal evidence based on case studies suggests a medium to large effect size (Cohen’s d > 0.80) for the primary outcome measures (PANSS mean score).
Using Gpower (version 3.1.0), statistical power was estimated for the proposed sample sizes (n=10 in each group) and an alpha level of 0.05, for an effect size of >0.80 (Cohen’s d estimate). Calculations show that this study will possess a convincing capacity to detect medium to large effect size in key outcome measures with satisfactory statistical power.
Factorial repeated measures analysis of variance will be used to evaluate the change of psychopathology over time. The between group factor will be Quercetin versus Placebo and the within group factor will be the five assessments (baseline and four follow-up assessments).

Recruitment
Recruitment status
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)
WA
Recruitment hospital [1] 7434 0
Graylands Selby-Lemnos & Special Care Hospital - Mount Claremont
Recruitment postcode(s) [1] 15240 0
6010 - Mount Claremont

Funding & Sponsors
Funding source category [1] 295505 0
Hospital
Name [1] 295505 0
Graylands Hospital
Address [1] 295505 0
Brockway Rd
Mt Claremont
Western Australia
6010
Country [1] 295505 0
Australia
Funding source category [2] 295507 0
University
Name [2] 295507 0
University of Western Australia
Address [2] 295507 0
The University of Western Australia
35 Stirling Highway
CRAWLEY, WA 6009
Country [2] 295507 0
Australia
Funding source category [3] 295508 0
Commercial sector/Industry
Name [3] 295508 0
Bioceuticals
Address [3] 295508 0
Unit 1/ Level 1, 85 O'Riordan St
Alexandria 2015
New South Wales Australia
Country [3] 295508 0
Australia
Primary sponsor type
University
Name
University of Western Australia School of Medicine and Pharmacology
Address
The University of Western Australia
35 Stirling Highway
CRAWLEY, WA 6009
Country
Australia
Secondary sponsor category [1] 294326 0
None
Name [1] 294326 0
Address [1] 294326 0
Country [1] 294326 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296833 0
NMHS MH HREC
Ethics committee address [1] 296833 0
NMHS-MH REGO
Executive Officer
Gascoyne House, Graylands Campus
Locked Bag No. 1
PO CLAREMONT WA 6910
Ethics committee country [1] 296833 0
Australia
Date submitted for ethics approval [1] 296833 0
13/02/2017
Approval date [1] 296833 0
15/09/2017
Ethics approval number [1] 296833 0
Ethics committee name [2] 296835 0
University of Western Australia Human Research Ethics Committee (HREC)
Ethics committee address [2] 296835 0
The University of Western Australia
35 Stirling Highway
CRAWLEY, WA 6009
Ethics committee country [2] 296835 0
Australia
Date submitted for ethics approval [2] 296835 0
31/03/2017
Approval date [2] 296835 0
21/11/2017
Ethics approval number [2] 296835 0

Summary
Brief summary
The hypothesis for this study is that a proportion of patients with schizophrenia may not respond to medication because the medication does not cross the blood brain barrier well enough. The blood brain barrier keeps substances out of the brain and is made up of several parts. One part is a group of proteins called “efflux pumps” or “transporters” which act to pump foreign substances out of the brain, back into the blood stream. We believe that some patients who do not respond to medications for schizophrenia have such fast and efficient efflux pumps that the medications cannot get into the brain effectively.
The speed and efficiency of these efflux pumps are determined by the genes for these pumps. The particular pumps that are of interest in this study are called P-glycoprotein (PgP) and Breast Cancer Resistance Protein (BCRP).
This study will test the addition of a natural product, quercetin, to the patient’s regular medicine. Quercetin is known to slow down these pumps.
The aim of the study is:
To show that quercetin has beneficial effects when added to the usual medications used in in schizophrenia
Objectives:
-To figure out the how quercetin has a beneficial effect.
-To identify the symptoms of schizophrenia which responded best to quercetin use
-To see if there are groups of genes that indicate fast efflux pumps in patients with schizophrenia who do not improve with the usual medications.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72170 0
Mr Darren Schwartz
Address 72170 0
Pharmacy Department
Graylands Hospital
Brockway Rd
Mt Claremont
WA
6010
Country 72170 0
Australia
Phone 72170 0
+61893476400
Fax 72170 0
+61 8 93844586
Email 72170 0
darren.schwartz@health.wa.gov.au
Contact person for public queries
Name 72171 0
Mr Darren Schwartz
Address 72171 0
Pharmacy Department
Graylands Hospital
Brockway Rd
Mt Claremont
WA
6010
Country 72171 0
Australia
Phone 72171 0
+61893476400
Fax 72171 0
+61 8 93844586
Email 72171 0
darren.schwartz@health.wa.gov.au
Contact person for scientific queries
Name 72172 0
Mr Darren Schwartz
Address 72172 0
Pharmacy Department
Graylands Hospital
Brockway Rd
Mt Claremont
WA
6010
Country 72172 0
Australia
Phone 72172 0
+61893476400
Fax 72172 0
+61 8 93844586
Email 72172 0
darren.schwartz@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Study protocol
Ethical approval
How or where can supporting documents be obtained?
Type [1] 5835 0
Study protocol
Citation [1] 5835 0
Link [1] 5835 0
Email [1] 5835 0
darren.schwartz@health.wa.gov.au
Other [1] 5835 0
Attachment [1] 5835 0
Type [2] 5836 0
Ethical approval
Citation [2] 5836 0
Link [2] 5836 0
Email [2] 5836 0
darren.schwartz@health.wa.gov.au
Other [2] 5836 0
Attachment [2] 5836 0
Summary results
No Results