Standardizing Care for Neuropsychiatric Symptoms and Quality of Life in Dementia (StaN)

The object of this study to evaluation an Integrated Care Pathway (ICP) to treat Aggression and Agitation in Alzheimer's disease (AD-AA). The ICP is an algorithmic approach to use psychotropic medications and non-pharmacological interventions based on standardized assessments which fosters measurement-based decision making. This study will assess the efficacy of the ICP to treat AD-AA and its impact on inappropriate use of medications in inpatient settings and Long-Term Care Facilities (LTCF).

The investigators will enroll and randomize 220 participants with AD-AA (110 inpatient and 110 LTCFs) to ICP vs. Treatment As Usual. Further, this study will also examine the impact of the ICP on caregiver burden and undertake a cost-effectiveness analysis of the ICP for patients with AD-AA.

Study Overview

• Status: Active, not recruiting
• Conditions: Aggression; Alzheimer's Disease; Alzheimer Dementia (AD)
• Intervention / Treatment: Behavioral: Non-Pharmacological Intervention; Other: Pharmacological Intervention

Detailed Description

This project will take place in 7 sites across two settings: Inpatient (CAMH in Toronto, Douglas Hospital Research Centre in Montreal, Parkwood Institute in London, and the University of Calgary in Calgary); and LTCFs affiliated with CAMH in Toronto and Parkwood Institute in London.

After a project initiation phase of 6 months, the investigators will enroll and randomize 220 participants with AD-AA (110 inpatient and 110 in LTCFs) to ICP vs.TAU. In this randomized control trial (RCT) phase of the project, participants will be treated for 12 weeks. There will be two primary outcome measures: (i) the Cohen-Mansfield Agitation Inventory (CMAI) Total Frequency Score (CMAI-frequency) and (ii) the proportion of participants on polypharmacy. These measures will be conducted at baseline, end of non-pharmacological intervention phase, the mid-point of pharmacological interventions and end of RCT. Neuropsychiatric Inventory-Questionnaire (NPI-C) will be used to assess global burden of neuropsychiatric symptoms at baseline, end of non-pharmacological intervention phase and exit. The modified Clinical Global Impression of Change (CGIC) will also be measured at predetermined time points throughout the 12 weeks to determine response as defined by CGIC < 3. CGIC is a 7-point Likert scale to rate each patient along a continuum from marked improvement to marked worsening, based on global clinical impression. Rating of < 3 indicates moderate or marked improvement in agitation as compared to baseline. At the end of the RCT, each participant will be naturalistically followed up for an additional 6 months during which the investigators will collect both clinical and health economics data from the Institute for Clinical Evaluative Sciences (ICES) database. The RCT phase will be completed after 18 months, and during the last part of this project, the investigators will analyze the data from the RCT and complete all naturalistic follow-ups.

• Study Type: Interventional
• Enrollment (Actual): 187
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • University of Calgary
  • Ontario
    • Kingston, Ontario, Canada, K7L 4X3
      • Providence Care
    • London, Ontario, Canada, N6C 2R5
      • Lawson Health Research Institute
    • Toronto, Ontario, Canada, M6J 1H4
      • Centre for Addiction and Mental Health
    • Whitby, Ontario, Canada, L1N 5S9
      • Ontario Shores Centre for Mental Health Sciences
  • Quebec
    • Montréal, Quebec, Canada, H4H 1R3
      • Douglas Hospital Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. A clinical diagnosis of Dementia of Alzheimer's or Mixed type using the Diagnostic and Statistical Manual of Mental Disorders, 5th Ed. (DSM-5) criteria
2. AD-AA as defined by Agitation in cognitive disorders; International Psychogeriatric Association provisional consensus clinical and research definition
3. Participant or substitute decision maker (SDM) able and willing to provide consent for enrollment in the study
4. 50 years or older
5. Medical stability to participate in the trial.

Exclusion Criteria:

1. Having dementia other than Alzheimer's or Mixed type.
2. DSM-5 diagnoses other than dementia that is thought to be significantly impacting the presentation of AD-AA such as delirium, bipolar disorder, or major depressive disorder.
3. Any other reason which in the opinion of study investigator will make the study participation intolerable for the participant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: The Integrated Care Pathway (ICP) Arm; The ICP consists of 1) a cleanup phase during which a thorough assessment of pharmacotherapy to discontinue unnecessary medications, is performed; 2) Structured non-pharmacological interventions, which would have started as soon as randomization occurred and would continue before any pharmacological intervention for 2 weeks as stand-alone interventions; and 3) a pharmacological intervention phase: in this phase the medications algorithm for AD-AA is initiated.	Behavioral: Non-Pharmacological Intervention; The behavioural intervention will be a structured implementation of individualized activities to be followed and customized as per the needs of the participant.; Other Names: Behavioural Intervention; Other: Pharmacological Intervention; The medication algorithm provides recommendations to the treatment team about algorithmic treatment and assessments as per the ICP but ultimately the decision to prescribe any particular intervention will be the treatment team's decision and the recommendations of the research team for ICP arm will not be binding for the treatment team.
No Intervention: Treatment-As-Usual (TAU) Arm; Following eligibility and baseline assessments, half of the participants will be randomized to TAU. TAU will consist of the typical care that the interdisciplinary team provides at each site for AD-AA. No predetermined cleanup phase, non-pharmacological interventions, algorithmic pharmacological interventions will be systematically part of TAU.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cohen-Mansfield Agitation Inventory - Total Frequency Score (CMAI - Frequency)	The Cohen-Mansfield Agitation Inventory (CMAI) Frequency score measures burden of agitation in patients with dementia. CMAI-frequency score ranges between 29 to 203, higher scores indicate worsening of symptoms.	Conducted at baseline, 3 weeks, 8 weeks, and 12 weeks
The proportion of participants on polypharmacy	The percentage and the total number of participants on 2 or more psychotropics	Data collected at baseline, 3 weeks, 8 weeks, and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The impact of the ICP on falls	Recording the number of falls	Every 2 weeks

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Collaborators: University of Calgary; Lawson Health Research Institute; Douglas Mental Health University Institute
• Investigators: Principal Investigator: Tarek Rajji, MD, Centre for Addiction and Mental Health

Publications and helpful links

General Publications

• Zarei S, Colman S, Rostas A, Burhan AM, Chu L, Davies SJ, Derkach P, Elmi S, Hussain M, Gerretsen P, Graff-Guerrero A, Ismail Z, Kim D, Krisman L, Moghabghab R, Mulsant BH, Nair V, Pollock BG, Rej S, Simmons J, Van Bussel L, Rajji TK, Kumar S; StaN Study Group. The Rationale and Design of Behavioral Interventions for Management of Agitation in Dementia in a Multi-Site Clinical Trial. J Alzheimers Dis. 2022;86(2):827-840. doi: 10.3233/JAD-215261.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): March 31, 2023
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: September 13, 2018
• First Submitted That Met QC Criteria: September 13, 2018
• First Posted (Actual): September 14, 2018

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Dementia; Aggression; Agitation; Integrated Care Pathway; StaN
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Aggression; Dementia; Alzheimer Disease
• Other Study ID Numbers: 1482 (CSL Behring)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No