Study of Mirtazapine for Agitation in Dementia

NCT03031184 | Completed Phase 3 DMC

• 1 other identifier: 15/SC/0606
• Study Type: interventional
• Target: 207
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Dementia

Keywords

Agitation; Agitated behaviours; Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline, 6 weeks, 12 weeks

Study Arms (2)

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.

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.

Other: Placebo

Interventions

Mirtazapine DRUG

Mirtazapine

Placebo OTHER

Also known as: Dummy pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Sussex: lead
• Norwich Clinical Trials Unit: collaborator
• University of East Anglia: collaborator
• University of Cambridge: collaborator
• University College, London: collaborator
• London School of Economics and Political Science: collaborator
• University of Manchester: collaborator
• University of Newcastle Upon-Tyne: collaborator
• Birmingham and Solihull Mental Health NHS Foundation Trust: collaborator
• Alzheimer's Society: collaborator
• The Centre for Dementia Studies, Brighton and Sussex Medical School and SPFT: collaborator

Study Sites (1)

Sube Banerjee

Brighton, Sussex, BN1 9RY, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 37929672 DERIVED

• Banerjee 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.

  PMID: 34688369 DERIVED

MeSH Terms

Conditions

Dementia; Psychomotor Agitation; Alzheimer Disease

Interventions

Mirtazapine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Dyskinesias; Neurologic Manifestations; Psychomotor Disorders; Neurobehavioral Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sube Banerjee, Professor

  Brighton and Sussex Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2017
• First Posted: January 25, 2017
• Study Start: January 1, 2017
• Primary Completion: June 1, 2020
• Study Completion: March 1, 2021
• Last Updated: April 19, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After analysis by the study team is complete, likely from October 2022. The above documents are already available
• Access Criteria: By email request to Prof Sube Banerjee sube.banerjee@plymouth.ac.uk

Locations

GB (1)