Clinical Trials Unit (incorporating Cadence Clinical Trials)

Overview

Initially funded by the John Cade Fellowship, the Cadence Clinical Trials Program was established to find better treatments for psychotic disorders, linking QCMHR clinical researchers, staff from the Queensland Brain Institute, and clinicians around south-east Queensland to:

• build a clinical trials platform in South-East Queensland
• work towards improving clinical outcomes for people with psychosis, particularly early psychosis
• concentrate on “augmentation” or add-on studies that are pragmatic in design
• investigate safer and more effective treatments
• develop introductory clinical trials training to foster the next generation of researchers

Genesis of the program

Professor John McGrath was awarded a John Cade Fellowship in Mental Health Research by the National Health and Medical Research Council (NHMRC) in 2013 (NHMRC grant APP1056929). This five-year grant supported Professor McGrath’s research into modifiable risk factors for schizophrenia.

Most importantly, the Fellowship enabled Professor McGrath and his team to establish the Cadence Clinical Trials platform in South-East Queensland to improve clinical outcomes for people with psychosis, particularly early psychosis.

The first trial, Cadence BZ, commenced in 2015, with other trials following over subsequent years. The program was strengthened by collaborations with the Royal Australian and New Zealand College of Psychiatrists (RANZCP) to build capacity in the next generation of mental health researchers.

The John Cade Fellowship has now come to an end, but the Cadence Clinical Trials team has now morphed into our Clinical Trials Unit, and under Andrea Baker’s leadership, has become QCMHR’s ninth research stream supporting a new generation of clinical trials. It continues to operate under the auspices of the Queensland Centre for Mental Health Research (West Moreton Hospital and Health Service) and the Queensland Brain Institute (The University of Queensland).

QCMHR is immensely grateful for the support of the John Cade Fellowship, which enabled us to establish this clinical trials capability and improve outcomes for people with psychosis long into the future.

 Cadence working group: L to R (floor) Alex Ryan, Andrew Amos, Sue Patterson, Victoria Gore-James, Justin Chapman L to R (back row) Julanne Frater, Kara Forde, Melissa Connell, Ros Cole, Andrea Baker, John McGrath, Anne Gordon, Elinor HIggs, Michael Duhig, Phillip Williams, Saveenah Singh, Victoria Satchwell, Rachel Petro, Alison Bowers, Frances Dark, James Scott, Vinod Raveendran, Michael Berk, Olivia Dean.

Further reading

To find out about other aspects of Professor McGrath’s John Cade Fellowship, for example his vitamin D research, read his article The John Cade Fellowship: Modifiable risk factors for serious mental illness published in the Australian and New Zealand Journal of Psychiatry in 2014.

We want immediate, complete and sustained recovery for everyone who experiences serious mental illness, with no harmful side effects.

We want better outcomes for people with psychosis, thus we need safer and more effective treatments.

Clinical trials are the best way to test new interventions, which could be medications, psychosocial interventions, models of service etc.

The NHMRC John Cade Fellowship allowed us to build a clinical trials capacity and to improve general literacy (i.e. understanding) of why clinical trials are an important part of health services.

In this video, Professor John McGrath describes his vision for the Cadence trials – a vision that still holds true today.

Clinical trials are the gold standard for testing new treatments

We must not be content with current treatments. Our patients deserve better treatments and they need this urgently.

The wisdom of clinicians and discoveries from brain sciences will generate new ideas for treatment, but we need efficient ways to test candidate treatments in clinical settings.

Health research is everyone’s business – research is the “R and D” (i.e. research and development) arm of the health sector. Australia spends $130 billion dollars a year on health services. We need a greater investment in research that results in better treatments.

Clinical trials are the gold standard way to test new treatments.

In this video Professor McGrath explains how clinical trials will help us find better treatments for people with serious mental illness.

Current treatments

Current treatments for early psychosis are a combination of medication and psychosocial intervention (e.g. therapy and practical support).

However, current medications have a range of undesirable side effects such as sedation, weight gain and impairment of sexual function. Even with the best possible care, some people with early psychosis do not make a full recovery.

In this video Associate Professor James Scott describes the current treatments for early psychosis.

In this video Associate Professor James Scott explores some of the problems with current treatments.

Finally, Associate Professor James Scott describes what kind of treatments patients want.

Australian Early Psychosis Network

Over the last three decades Australian researchers have pioneered new conceptual models related to the identification of those with early psychosis.

Professor Patrick McGorry was named Australian of the Year in 2010 for his efforts to deliver good mental health care to those in the earliest phases of psychosis.

We now need to mirror that sense of innovation with new treatments.

In 2014, the Australian Early Psychosis Network was established to build research and clinical capacity.

The Cadence project hopes to contribute to that initiative.

In this video Professor McGrath explains why the treatment of early psychosis is such a promising area for clinical trials.

Further reading

Read the 2010 Survey of High Impact Psychosis (SHIP) for a better understanding of the prevalence of psychosis in Australia, and the lives of people living with psychosis.

Cadence BZ Trial

Cadence BZ was the first clinical trial in the Cadence series. The trial aimed to determine if receiving a commonly used food preservative, in addition to regular treatments, assisted with recovery from early psychosis.

The food preservative, sodium benzoate, is commonly used in soft drinks, fruit juices, jams and salad dressings (on labels it is often listed as E211). The US Food and Drug Administration has classified sodium benzoate as “generally recognised as safe” and it is approved in Australia as a food additive. It is also sometimes used to help preserve other medications.

However sodium benzoate is not approved to treat psychosis. Therefore it is an experimental treatment for psychosis, and must be rigorously tested to find out if it is an effective add-on treatment.

Project team

• Professor John McGrath, Coordinating Principal Investigator, QCMHR
• Professor James Scott, Principal Investigator, QCMHR
• Andrea Baker, Study Coordinator, QCMHR
• Dr Drew Richardson, Associate Investigator, The Prince Charles Hospital
• Dr Savenna Singh, Associate Investigator, Gold Coast University Hospital
• Dr Frances Dark, Associate Investigator, Princess Alexandra Hospital
• Dr Sean Hatherill, Associate Investigator, Logan Hospital
• Associate Professor Stephen Stathis, Associate Investigator, Queensland Children’s Hospital
• Dr Sharon Foley, Associate Investigator, Princess Alexandra Hospital

Cadence M

Cadence M was the second clinical trial in the Cadence series*. The trial aimed to determine if receiving an extract from the rind of the tropical fruit mangosteen, in addition to regular treatments, assists with the treatment of schizophrenia.

Mangosteen is a tropical evergreen fruit tree originating in Indonesia. The thick purple rind (pericarp) of the fruit contains a number of compounds called xanthones that show promise in the treatment of schizophrenia.

Many of the most valuable drugs in medicine are plant-derived (e.g. morphine, quinine). Pilot studies suggest that certain xanthones derived from mangosteen pericarp significantly reduce the symptoms of schizophrenia.

The team sought to replicate the results of the pilot study in a larger, multi-site trial.

Project Team

• Professor Michael Berk, Coordinating Principal Investigator, Deakin University
• Professor John McGrath, Principal Investigator, QCMHR
• Andrea Baker, Study Coordinator, QCMHR
• Professor James Scott, Associate Investigator QCMHR
• Dr Seetal Dodd, Associate Investigator, University Hospital Geelong
• Dr Olivia Dean, Associate Investigator, Deakin University
• Dr Frances Dark, Associate Investigator, Princess Alexandra Hospital

*The Cadence M trial was also known as Mango SZ at our companion site in Geelong.

Cadence M was supported by the Stanley Medical Research Institute.

Cadence CoMET Trial

Cadence CoMET was the fourth clinical trial in the Cadence series. The CoMET trial examined if starting a diabetes medication called metformin at the same time as the antipsychotic medication clozapine could minimise the weight gain that can occur with clozapine treatment.

Metformin is a commonly used medication for diabetes but is not approved by the Therapeutic Goods Administration (TGA) for weight loss. Previous research however, has found it to promote weight loss in people who have gained weight after clozapine treatment.

People with schizophrenia are known to have a shorter life expectancy due to diseases such as heart disease and diabetes. This is a result of many factors including obesity, poor diet, reduced physical activity and antipsychotic medications. Antipsychotic medications are an essential part of current treatment for schizophrenia and schizoaffective disorder so it is important to examine treatments to target these side effects.

Physical activity programs have been shown to be effective in improving the physical health and weight management for some people taking antipsychotic medications but not all. For this reason it is important to explore other options for improving the physical health of people taking antipsychotic medications.

Project Team

• Professor Dan Siskind, Coordinating Principal Investigator, Metro South Addiction and Mental Health Service
• Dr Terry Stedman, Associate Investigator, West Moreton Divison of Mental Health and Specialised Services
• Associate Professor Anthony Russell, Associate Investigator, Princess Alexandra Hospital
• Dr Vikas Moudgil, Associate Investigator, Royal Brisbane and Women’s Hospital
• Dr Savio Sardinha, Associate Investigator, Gold Coast Hospital and Health Service
• Associate Professor Sue Patterson, Royal Brisbane and Women’s Hospital
• Andrea Baker, Study Coordinator, QCMHR

Cadence SCIT Trial

The trial aimed to determine if receiving social cognition and interaction training (SCIT) improves psychosocial functioning in people with schizophrenia. The treatment was compared with another type of group therapy that helps people recover from mental disorders.

Functional deficits (i.e. social skill, community functioning) are a core feature of schizophrenia. These deficits are not always improved via medication. While established treatments like social skills training and cognitive remediation improve the specific skills they target, these changes may not help people cope with aspects such as socializing.

Project Team

• Dr Frances Dark, Coordinating Principal Investigator, Director of Rehabilitation Academic Clinical Unit, Metro South Mental Health Services

As a new group we need to be strategic. In the first few years of Cadence we will concentrate on ‘augmentation’ or add-on studies, where everyone still receives standard care, but patients are randomized to a candidate treatment or placebo.

Also, we will concentrate on interventions that are safe and more readily acceptable to people with early psychosis.

We will undertake high-quality ethical research, based on respect for participants and clinicians. We are keen for people with psychosis (and their families) to understand the importance of clinical trials, and help us develop better treatments in the decades ahead.

We want to do studies that are as ‘pragmatic’ as possible i.e. that accept a wide range of participants, that do not disrupt ordinary clinical care, and that concentrate on clinically meaningful outcomes.

What does “Cadence” mean?

The name “Cadence” has many musical connotations including rhythm, harmony and balance. It also pays tribute to John Cade. In this video Professor McGrath explains why he chose the name Cadence.

Partnership with citizen scientists

In this video Associate Professor James Scott explains how the Cadence team wants to work in partnership with people with early psychosis as “citizen scientists”.

John Cade was an Australian psychiatrist who discovered the effectiveness of lithium as a treatment for bipolar disorder in 1949. This discovery was a major breakthrough in the treatment of mental illness.

Dr Cade is an inspiring example of a researcher who was tenacious and clinically astute.

Visit Wikipedia for more information about John Cade’s life and work. The prestigious NHMRC John Cade Fellowship in Mental Health Research, which is funding the Cadence project, is named in his honour.

In this video Professor McGrath pays tribute to Dr Cade’s remarkable achievements.

Further reading

To understand the significance of John Cade’s breakthrough, and the circumstances in which it occurred, read Philip Mitchell’s article On the 50th anniversary of John Cade’s discovery of the anti-manic effect of lithium published in the Australian and New Zealand Journal of Psychiatry in 1999.

Cadence COaST

Weight gain is a major health problem among people with schizophrenia; there is a lack of effective treatments for obesity in schizophrenia. We are looking for volunteers to determine if receiving a weekly injectable Type-II diabetic medication, semaglutide can assist in reducing the body weight among non-diabetic people taking clozapine.

Study details:
• 36-week single-blind clinical trial
• Weekly injection of semaglutide or placebo (titrated over 20 weeks, i.e., 4 weeks per titrated dose 0.25mg, 0.5mg, 1.0mg, 1.5mg, 2.0mg)
• Physical health measures (blood pressure, heart rate, height, and weight) and assessment of adverse drug reactions
• Validated mental health and psychological clinical measures will be conducted at Baseline, Weeks 20 and 36
• All assessments completed by Cadence Team 
• Adjunct treatment; no restrictions or impact on current treatment
• Semaglutide/placebo trial medication provided at no cost
• Reimbursement: $290 in Coles/Myer gift cards ($50 at baseline, weeks 20 and 36). ($20 at weeks 4, 8, 12, 16, 24, 28 and 32)

Inclusion Criteria:
• Aged 18 - 64 years (inclusive).
• Have received oral clozapine for at least 18 weeks
• Diagnosis of schizophrenia or schizoaffective disorder or bipolar affective disorder
• Not been treated for diabetes or have an abnormal HbA1c/fasting glucose at baseline
• Body weight has not fluctuated by more than ±5% in the previous 3 months
• BMI ≥26
• Participants must have the capacity to consent and be able to follow the study instructions and procedures
• Participants must be a consumer of a public mental health service in South East QLD

Semaglutide will be slowly increased to minimise any side effects but possible side effects of semaglutide include nausea, vomiting, diarrhea and constipation. Participants will be monitored weekly by experienced research staff for side effects.

The trial has been reviewed and approved by Metro South Human Research Ethics Committee.

Contact:
For more information please contact us at This email address is being protected from spambots. You need JavaScript enabled to view it. or on 07 3271 8704

Cadence Can-Cloz

Cannabidiol (CBD) is a compound that is found in cannabis. CBD is non-psychotropic which means it does not affect perception, mood, or behaviour (unlike THC). In this study, we are trying to determine whether CBD can assist in reducing symptoms for people with schizophrenia or schizoaffective disorder.

Study details:

• 12-week study trial
• Allocated into 1 of 2 groups:
  Active – 1000mg CBD
  Placebo – non-active capsules
• 5 capsules in the evening
• 1x 60-minute research session every 2 weeks
• Phone call follow-ups every other week to monitor for any side effects
• Add-on treatment – this will not affect your current treatment and you will stay on all your regular medications
• Currently taking clozapine for at least 18 weeks
• Blood tests at the beginning, middle and end of the study
•  Option to provide saliva for DNA collection
• Up to $140 in gift vouchers provided throughout study
• All research is completely voluntary. Participants can withdraw from the study at any time.

Inclusion Criteria:

• Aged 18 - 64 years (inclusive)
• Have received oral clozapine for at least 18 weeks
• Diagnosis of schizophrenia or schizoaffective disorder
• Total PANSS score ≥ 60
• Participants must have the capacity to consent and be able to follow the study instructions and procedures (i.e., not under Public Guardian for health matters)
• Participants must be a consumer of a public mental health service in South East QLD

Previous studies have shown that CBD was well tolerated by participants with a mild side-effect profile. Such side effects can include nausea, appetite changes, and fatigue. Participants will be monitored weekly by experienced research staff for side effects.

The trial has been reviewed and approved by Metro South Human Research Ethics Committee.

Contact:
For more information please contact us This email address is being protected from spambots. You need JavaScript enabled to view it. or on 07 3271 8704

Cadence Discovery

Sodium benzoate is a commonly used food preservative that has been shown to have the potential to reduce overall symptoms of schizophrenia. In this study, we are trying to replicate those results and determine what is the most effective dose to show change.

Study details:

• 6-week study trial
• Allocated into 1 of 4 groups:
  • 1g sodium benzoate
  • 2g sodium benzoate
  • 4g sodium benzoate
  • Placebo (non-active group)
• 4 tablets morning and night
• 1x 60-minute screening session at baseline
• 1x 60-minute research session every 2 weeks
• Phone call follow-ups every other week to monitor for safety
• Add-on treatment – this will not affect your current treatment and you will stay on all your regular medications
• Optional blood test at start and end of study
• Up to $100 in gift vouchers for study completion
• All research is completely voluntary, and you can withdraw from the study at any time.

Inclusion criteria:

• Aged between 18 and 64 years (inclusive)
• Fulfil the DSM-IV criteria for schizophrenia, based on the Diagnostic Interview for Psychosis
• Diagnosis of schizophrenia
• Have a Positive and Negative Syndrome Scale (PANSS) total score ≥60
• Have received antipsychotic medications for a period of at least one continuous month prior to assessment for the study and remained symptomatic despite taking antipsychotic therapy
• Agree to participate, has capacity to consent and is able to follow the study instructions and procedures
• Effective use of contraception (females only)
• Participants must be a consumer of a public mental health service in South East QLD

Previous studies have shown that sodium benzoate was well tolerated by participants with a low side-effect profile. Participants will be monitored by experienced research staff for side effects and can withdraw from the study at any time.

The trial has been reviewed and approved by QIMR Berghofer Research Ethics Committee.

Contact:
For more information please contact us at This email address is being protected from spambots. You need JavaScript enabled to view it. or on 07 3271 8704