Frequently Asked Questions

What is ASCEnD?

ASCEnD is a clinical trial for people who have bipolar and are currently experiencing depression. It is comparing the combination of 2 drugs (aripiprazole and sertraline) with a single drug (quetiapine). Half of the patients in the trial, who will be chosen at random, will be offered the drug combination (aripiprazole and sertraline) and the other half will be offered quetiapine. You and your doctors will know exactly what medication you are prescribed.

All of these drugs are already commonly used in the NHS, and their safety is well known. Quetiapine is currently the most used treatment for depression in bipolar. We know that aripiprazole combined with an antidepressant drug like sertraline works well in people who are depressed but don’t have bipolar. This trial will confirm whether or not it also works in people who are depressed and do have bipolar.

Who can participate and where?

You may be able to take part if you:

  1. Have bipolar

  2. Are currently experiencing depression

  3. Are over the age of 18

  4. Not currently pregnant or breastfeeding or planning to become pregnant during the trial

The study is taking part across 10 Mental Health Trusts in England: Birmingham & Solihull Mental Health Foundation Trust; Sussex Partnership NHS Foundation Trust; Avon & Wiltshire Mental Health Partnership Trust; Camden and Islington NHS Foundation Trust; Cornwall Partnership NHS Foundation Trust; Cumbria, Northumberland, Tyne and Wear NHS Trust; Nottinghamshire Healthcare Trust; Oxford Health NHS Foundation Trust; Southern Health NHS Foundation Trust; Tees, Esk & Wear Valleys NHS Foundation Trust.  For more information, please see: Sites — The ASCEnD Trial

How can I get involved?

There are several routes to take part in the study:

  • ASCEnD is working in collaboration with Reserach + Me. Research+Me is a Newcastle Upon Tyne based registry for people who want to find out about opportunities to take part in research. When you register with Research+Me, you will be prompted to fill in a registration form, which will help us to understand whether you might be eligible to take part in ASCEnD. You can follow this link to register: https://redcap.link/rpm-ascend

  • You might be able to contact the trial site directly when they are open to recruitment. Contact details for the sites accepting self-referrals will be added on this page.

  • Your care provider can also register you to the trial. We are recruiting from both GPs and hospitals. a list of our collaborating sites can be found on this page. page

What does taking part involve?

You will take part in the trial for 24 weeks. Taking part will involve 1 or 2 face-to-face appointments (most likely 1), which will include:

  1. Discussing the trial with a trial doctor who will answer any questions you may have before you decide whether or not to take part. If you decide to take part you’ll be asked to sign a consent form.

  2. Confirming if you are eligible to take part. This will include completing some questionnaires, and discussing your medical history and medication.

You can enter the trial if you and your doctor think that quetiapine or the drug combination would be equally good choices as the next step in your treatment. In the trial, you will be randomly selected by a computer to start one treatment or the other. If the treatment suits you and seems to be working then you will be able to continue it. If it isn’t, then you don’t need to, and you and your doctor can change to something else.

 

During the trial, you will be asked to complete a number of questionnaires on a weekly basis. This will be done electronically(or over the phone), and you will receive a weekly phone call from a member of the research team for support.

 

How might the study help?

NICE currently recommends olanzapine (with or without fluoxetine), quetiapine or lamotrigine for the treatment of  bipolar depression. These drugs don’t work for everyone and cause side effects in many.  The study has the potential to make a new safe and effective drug regime available for people with bipolar disorder.    

Is there a payment for taking part in the study?

You will be given up to £50, as a thank you for giving your time for the trial. You may be also reimbursed for reasonable travel costs during your participation.

Why do we need this trial?

We need this trial to improve the lives of those who are suffering from severe bipolar depression. A participant must score 10 or more on QIDS-SR questionnaire for depression to be eligible for participation in the trial. This means that despite receiving their current treatment, they are still experiencing a depressive state which leaves significant room for improvement. During the change of medication process, participants’ progress is closely monitored which should allow for informed dose adjustments.

Why has this combination of medications been chosen to be studied?

The treatment of bipolar depression in clinical practice can often be difficult. There are three main medication options recommended by NICE (The National Institute for Health and Care Excellence, 2014). These don’t necessarily work for everyone and can sometimes cause side-effects. Antidepressants, when used alone, are not recommended for the treatment of bipolar depression.

Aripiprazole is already used to treat and prevent mania in bipolar disorder. Unlike two of the NICE recommended treatments, aripiprazole is much less likely to cause weight gain, diabetes or raised cholesterol. It is also used in the treatment of depression in people who don’t have bipolar disorder. In this case, it is usually combined with another antidepressant such as an SSRI (selective serotonin reuptake inhibitor).

Quetiapine is currently the most commonly used medication for the treatment of bipolar disorder.

The ASCEnD study is designed to see whether a combination of aripiprazole with an SSRI (sertraline) is better than quetiapine in the management of bipolar depression.

How long has the trial medication been around/approved?

The FDA license dates for the trial medication are as follows:

Aripiprazole: 2002 (for schizophrenia)

Sertraline: 1991 (for depression)

Quetiapine: 1997 (for schizophrenia)

Is the quetiapine medication instant or moderate release?

For the purposes of this trial, prescribing should follow standard clinical practice. Quetiapine is available in both an immediate release (IR) and in an extended release (XL) formulation. The choice between IR and XL will be decided by the treating doctor for participants randomised to quetiapine to ensure tolerability and minimise side-effects.

What is the maximum dose of Aripriprazole?

The maximum licensed dose of Aripiprazole for treatment of schizophrenia is 30mg daily but for the purpose of ASCEnD we are recommending much lower doses (2.5 to 10mg daily) as the evidence and clinical experience suggests these are better for treating bipolar depression.

Is there risk associated with changing from current medications?

The risk associated with changing from current medications for the study is no different to changing medication in routine clinical practice. The risk is minimised by offering support to treating clinicians by offering a ‘ASCEnD Medication Guide for Clinicians’ which outlines helpful practice.

The study does not mandate use of specific medication dosages or dose escalation procedures. Instead, clinicians are encouraged to use their judgement in accordance with clinical guidelines, the British National Formulary (BNF) dose schedule and this guidance. Dosage decisions and decisions regarding the ongoing use of study medications taken during the study remain the responsibility of the prescribing clinician who will make collaborative medication choices jointly with the patient. This means that the dosage is chosen collaboratively and can be suited to the participant’s specific clinical needs.

Who is running this trial?

 This study is being run with the support of the NHS and the National Institute for Health and Care Research (NIHR), working in partnership with Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust and Newcastle University.

What does the sponsor do?

The sponsor for this trial is the Research & Development department at Cumbria, Northumberland, and Tyne & Wear NHS Foundation Trust who take overall responsibility for all trial activity.

What is the qualitative nested study?

The qualitative sub-study has been designed in collaboration with researchers at Keele University to assess a number of factors related to the treatment of bipolar disorder in various settings. It will assess the efficiency and appropriateness of recruitment to the main study and help to give context to the study as a whole. Through semi-structured interviews with patients, GPs and psychiatrists, this nested study will gather perspectives on individual diagnosis pathways, GP prescribing processes, and attitudes around medication.

Can the anti-depressant be used to treat mania?

No, antidepressants alone are likely to worsen the course of bipolar disorder and evidence suggests instead the benefits of combining antidepressants with an antimanic or mood stabiliser medication. Therefore, Sertraline (an antidepressant) is combined with Aripiprazole (an antimanic antipsychotic) in the active arm of ASCEnD.