DementiaPhase 3SYMBADNCT03031184
Study of Mirtazapine for Agitation in Dementia
A Phase 3 study testing Mirtazapine in people with Dementia, run by University of Sussex at 1 site in United Kingdom.
Trial summary
This clinical trial evaluates whether Mirtazapine is more effective than placebo in treating agitation in people with dementia. The trial will assess the safety, clinical and cost effectiveness of the treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dementia
- What is being tested?
- Mirtazapine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 207 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2017to Mar 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with a clinical diagnosis of probable or possible Alzheimer's Disease using National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria (McKhann et Al, 1984)
- a diagnosis of co-existing agitated behaviours
- evidence that the agitated behaviours have not responded to management according to the AS/DH algorithm (AS/DH, 2011)
- An assessment of Cohen Mansfield Agitation Inventory (CMAI; Cohen-Mansfield et al, 1989, Long form) score of 45 or greater
- Written informed consent to enter and be randomised into the trial
- Availability of a suitable informant (consenting identifiable family carer or paid carer) to provide information on carer-completed outcome measures and who consents to take part in the trial.
Who cannot join
- Current treatment with antidepressants (including MAOIs) or antipsychotics. Normal clinical practice should be followed, with an appropriate washout period before trial drug administration. For MAOIs this should be least two weeks.
- Contraindications to the administration of mirtazapine as per the current SmPC
- Patients with second degree atrioventricular block (patients with third degree heart block, with a pace maker fitted, may be included at PI discretion)
- Cases too critical for randomisation (ie where there is a suicide risk or where the patient presents a risk of harm to others)
- Female subjects under the age of 55 of childbearing potential, defined as follows: postmenopausal females who have not had at least 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhoea with serum FSH>40mIU/ml or females who have not had a hysterectomy or bilateral oophorectomy at least 6 weeks prior to enrolment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pragmatic, Multi Centre, Double-blind, Placebo Controlled Randomised Trial to Assess the Safety, Clinical and Cost Effectiveness of Mirtazapine in Patients With Alzheimer's Disease (AD) and Agitated Behaviours
This clinical trial evaluates whether Mirtazapine is more effective than placebo in treating agitation in people with dementia. The trial will assess the safety, clinical and cost effectiveness of the treatment. Participants will be randomised to receive either Mirtazapine or placebo for 12 weeks and will be followed up for up to one year, in this blinded trial.
Read the detailed description
Patient-centred care, without the use of medicines is offered as a first course of treatment for agitation in dementia. However, there is a need for second line treatments when these fail, at the moment antipsychotics are commonly prescribed, as very little research has been done in to safer alternative treatments.
There are medicines available to treat agitation and/or aggression in dementia, but it is not clear which treatments work best.
This research study has been designed to help answer this, by comparing a which is currently prescribed for depression, Mirtazapine, with placebo (a tablet designed to look like a medicine but that has no active medicine in it) to see if Mirtazapine is suitable for treating agitation in dementia.
If participants and their family/carers agree to take part in this study, participants will be prescribed treatment for 12 weeks. Participants will then be followed up for 1 year after, with assessment sessions at 26 and 52 weeks.
Participants taking part in this study will be randomly allocated to a treatment group (selected to their treatment group by chance). The study is blinded, so this means the participant's doctor and the research team will not know which treatment the participant has been taking until after the study has ended. This is necessary so that the trial is a fair test of which treatment works best, however it is possible to find out which medicine they are taking in the event of a medical emergency.
The study is entirely voluntary and all participants wishing to join the study must complete an informed consent form (or if they lack capacity the participant's representative may do so on their behalf). Each participant must also have a nominated carer who consents to being questioned on aspects of the participant's dementia/care and their own experiences in caring for the participant.
The investigators are aiming to recruit 222 patients to the study in total from around 20 different regions across the UK.
The study was originally designed to included a second medication, called Carbamazepine, to also look at whether it would work and be safe and cost effective in agitation in dementia. Challenges in recruitment in this population resulted in the funder requesting that the available data was reviewed to July 2018, to see whether one of the arms (Mirtazapine or Carbamazepine) should be discontinued in terms of future recruitment. The independent data monitoring committee compared blinded data from both groups against placebo data and concluded that on the basis of efficacy and safety, the group, which when unblinded was found to be Carbamazepine, should be dropped. Some limited analysis will still be completed for all data collected in the Carbamazepine group, but the trial will continue now only randomising participants to Mirtazapine or placebo.
- Conditions
- Dementia
- Being tested
- Mirtazapine, Placebo
- Keywords
- Agitation, Agitated behaviours, Alzheimer's Disease
- Medical subject headings
- Dementia, Psychomotor Agitation, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MirtazapineDrug
PlaceboOther
Also called Dummy pill
| Study group | Role | What they receive |
|---|---|---|
| Mirtazapine | Experimental | 15mg of Mirtazapine over encapsulated to produce a blinded product that looks identical to the other arms. Starting dose is one capsule per day, escalating to 2 capsules per day after 2 weeks if no side effects and up to 3 capsules per day after 4 weeks. Receives: Drug: Mirtazapine |
| Placebo | Placebo comparator | Lactose powder encapsulated to produce a blinded product that looks identical to the other arms. Starting dose is one capsule per day, escalating to 2 capsules per day after 2 weeks if no side effects and up to 3 capsules per day after 4 weeks. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cohen Mansfield Agitation Inventory (CMAI) score (Long Form, 29 questions)
Measured at baseline, 6 and 12 weeks, it is the difference in the score at 12 weeks that is the primary outcome. The questions are asked of the person with dementia's carer
Measured: Baseline, 6 weeks, 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2017 (estimated)
- Study startJan 2017
- Primary completionJun 2020
- Study completionMar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DementiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 207 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sussex
- Sponsor type
- University, hospital or other
- Collaborators
- Norwich Clinical Trials Unit, University of East Anglia, University of Cambridge, University College, London, London School of Economics and Political Science, University of Manchester, University of Newcastle Upon-Tyne, Birmingham and Solihull Mental Health NHS Foundation Trust, Alzheimer's Society, The Centre for Dementia Studies, Brighton and Sussex Medical School and SPFT
- Responsible party
- Sponsor
- Investigators
- Sube Banerjee, Professor, Principal investigator, Brighton and Sussex Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03031184
- Sponsor's protocol ID
- 15/SC/0606
- Acronym
- SYMBAD
- Status last verified
- Apr 2021
- First submitted
- 3 Jan 2017
- Last updated
- 19 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: The datasets generated during the current study will be available upon request from Prof Sube Banerjee sube.banerjee@plymouth.ac.uk once the trial follow-up and analyses are completed, the likely date for this is October 2022.
Publications
Banerjee S, Farina N, Henderson C, High J, Stirling S, Shepstone L, Fountain J, Ballard C, Bentham P, Burns A, Fox C, Francis P, Howard R, Knapp M, Leroi I, Livingston G, Nilforooshan R, Nurock S, O'Brien J, Price A, Thomas AJ, Swart AM, Telling T, Tabet N. A pragmatic, multicentre, double-blind, placebo-controlled randomised trial to assess the safety, clinical and cost-effectiveness of mirtazapine and carbamazepine in people with Alzheimer's disease and agitated behaviours: the HTA-SYMBAD trial. Health Technol Assess. 2023 Oct;27(23):1-108. doi: 10.3310/VPDT7105.
PubMed 37929672Banerjee S, High J, Stirling S, Shepstone L, Swart AM, Telling T, Henderson C, Ballard C, Bentham P, Burns A, Farina N, Fox C, Francis P, Howard R, Knapp M, Leroi I, Livingston G, Nilforooshan R, Nurock S, O'Brien J, Price A, Thomas AJ, Tabet N. Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trial. Lancet. 2021 Oct 23;398(10310):1487-1497. doi: 10.1016/S0140-6736(21)01210-1.
PubMed 34688369
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pragmatic, Multi Centre, Double-blind, Placebo Controlled Randomised Trial to Assess the Safety, Clinical and Cost Effectiveness of Mirtazapine in Patients With Alzheimer's Disease (AD) and Agitated Behaviours
- ClinicalTrials.gov ID
- NCT03031184
- Acronym / sponsor ID
- SYMBAD / 15/SC/0606
- Conditions
- Dementia
- Keywords
- Agitation, Agitated behaviours, Alzheimer's Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 207 participants (actual)
- Lead sponsor
- University of SussexUniversity, hospital or other
- Collaborators
- Norwich Clinical Trials Unit, University of East Anglia, University of Cambridge, University College, London, London School of Economics and Political Science, University of Manchester, University of Newcastle Upon-Tyne, Birmingham and Solihull Mental Health NHS Foundation Trust, Alzheimer's Society, The Centre for Dementia Studies, Brighton and Sussex Medical School and SPFT
- Study start
- Jan 2017 (actual)
- Primary completion
- Jun 2020 (actual)
- Study completion
- Mar 2021 (actual)
- First posted
- 25 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial evaluates whether Mirtazapine is more effective than placebo in treating agitation in people with dementia. The trial will assess the safety, clinical and cost effectiveness of the treatment. Participants will be randomised to receive either Mirtazapine or placebo for 12 weeks and will be followed up for up to one year, in this blinded trial.
Detailed description
Patient-centred care, without the use of medicines is offered as a first course of treatment for agitation in dementia. However, there is a need for second line treatments when these fail, at the moment antipsychotics are commonly prescribed, as very little research has been done in to safer alternative treatments.
There are medicines available to treat agitation and/or aggression in dementia, but it is not clear which treatments work best.
This research study has been designed to help answer this, by comparing a which is currently prescribed for depression, Mirtazapine, with placebo (a tablet designed to look like a medicine but that has no active medicine in it) to see if Mirtazapine is suitable for treating agitation in dementia.
If participants and their family/carers agree to take part in this study, participants will be prescribed treatment for 12 weeks. Participants will then be followed up for 1 year after, with assessment sessions at 26 and 52 weeks.
Participants taking part in this study will be randomly allocated to a treatment group (selected to their treatment group by chance). The study is blinded, so this means the participant's doctor and the research team will not know which treatment the participant has been taking until after the study has ended. This is necessary so that the trial is a fair test of which treatment works best, however it is possible to find out which medicine they are taking in the event of a medical emergency.
The study is entirely voluntary and all participants wishing to join the study must complete an informed consent form (or if they lack capacity the participant's representative may do so on their behalf). Each participant must also have a nominated carer who consents to being questioned on aspects of the participant's dementia/care and their own experiences in caring for the participant.
The investigators are aiming to recruit 222 patients to the study in total from around 20 different regions across the UK.
The study was originally designed to included a second medication, called Carbamazepine, to also look at whether it would work and be safe and cost effective in agitation in dementia. Challenges in recruitment in this population resulted in the funder requesting that the available data was reviewed to July 2018, to see whether one of the arms (Mirtazapine or Carbamazepine) should be discontinued in terms of future recruitment. The independent data monitoring committee compared blinded data from both groups against placebo data and concluded that on the basis of efficacy and safety, the group, which when unblinded was found to be Carbamazepine, should be dropped. Some limited analysis will still be completed for all data collected in the Carbamazepine group, but the trial will continue now only randomising participants to Mirtazapine or placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mirtazapine | Experimental | Drug: Mirtazapine15mg of Mirtazapine over encapsulated to produce a blinded product that looks identical to the other arms. Starting dose is one capsule per day, escalating to 2 capsules per day after 2 weeks if no side effects and up to 3 capsules per day after 4 weeks. |
| Placebo | Placebo comparator | Other: PlaceboLactose powder encapsulated to produce a blinded product that looks identical to the other arms. Starting dose is one capsule per day, escalating to 2 capsules per day after 2 weeks if no side effects and up to 3 capsules per day after 4 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with a clinical diagnosis of probable or possible Alzheimer's Disease using National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria (McKhann et Al, 1984)
- a diagnosis of co-existing agitated behaviours
- evidence that the agitated behaviours have not responded to management according to the AS/DH algorithm (AS/DH, 2011)
- An assessment of Cohen Mansfield Agitation Inventory (CMAI; Cohen-Mansfield et al, 1989, Long form) score of 45 or greater
- Written informed consent to enter and be randomised into the trial
Key exclusion criteria (5 listed)
- Current treatment with antidepressants (including MAOIs) or antipsychotics. Normal clinical practice should be followed, with an appropriate washout period before trial drug administration. For MAOIs this should be least two weeks.
- Contraindications to the administration of mirtazapine as per the current SmPC
- Patients with second degree atrioventricular block (patients with third degree heart block, with a pace maker fitted, may be included at PI discretion)
- Cases too critical for randomisation (ie where there is a suicide risk or where the patient presents a risk of harm to others)
- Female subjects under the age of 55 of childbearing potential, defined as follows: postmenopausal females who have not had at least 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhoea with serum FSH>40mIU/ml or females who have not had a hysterectomy or bilateral oophorectomy at least 6 weeks prior to enrolment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mirtazapine | Drug | Mirtazapine |
| PlaceboAlso: Dummy pill | Other | Placebo |
Primary outcome
Cohen Mansfield Agitation Inventory (CMAI) score (Long Form, 29 questions)
Time frame: Baseline, 6 weeks, 12 weeks
Measured at baseline, 6 and 12 weeks, it is the difference in the score at 12 weeks that is the primary outcome. The questions are asked of the person with dementia's carer
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2021.
- Derived from this study: PubMed 37929672Banerjee S, Farina N, Henderson C, High J, Stirling S, Shepstone L, Fountain J, Ballard C, Bentham P, Burns A, Fox C, Francis P, Howard R, Knapp M, Leroi I, Livingston G, Nilforooshan R, Nurock S, O'Brien J, Price A, Thomas AJ, Swart AM, Telling T, Tabet N. A pragmatic, multicentre, double-blind, placebo-controlled randomised trial to assess the safety, clinical and cost-effectiveness of mirtazapine and carbamazepine in people with Alzheimer's disease and agitated behaviours: the HTA-SYMBAD trial. Health Technol Assess. 2023 Oct;27(23):1-108. doi: 10.3310/VPDT7105.
- Derived from this study: PubMed 34688369Banerjee S, High J, Stirling S, Shepstone L, Swart AM, Telling T, Henderson C, Ballard C, Bentham P, Burns A, Farina N, Fox C, Francis P, Howard R, Knapp M, Leroi I, Livingston G, Nilforooshan R, Nurock S, O'Brien J, Price A, Thomas AJ, Tabet N. Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trial. Lancet. 2021 Oct 23;398(10310):1487-1497. doi: 10.1016/S0140-6736(21)01210-1.
- Individual participant dataSharing planned: Yes. The datasets generated during the current study will be available upon request from Prof Sube Banerjee sube.banerjee@plymouth.ac.uk once the trial follow-up and analyses are completed, the likely date for this is October 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sube Banerjee, Professor principal investigator
Brighton and Sussex Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Mirtazapine in people with Dementia, run by University of Sussex at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cohen Mansfield Agitation Inventory (CMAI) score (Long Form, 29 questions) (time frame: Baseline, 6 weeks, 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03031184, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2021.