Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia

Alzheimer Disease Clinical Trial

— IMPACT-AD BC  

Official title:

Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia (IMPACT-AD BC)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05002699
• Other study ID #: H17-01339
• Status: Active, not recruiting
• Start date: February 1, 2019
• Est. completion date: March 2023

Study information

• Verified date: May 2022
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The 'Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia' (IMPACT-AD BC) study is an observational, longitudinal cohort study that will examine the impact of cerebrospinal fluid (CSF) testing for core Alzheimer's disease biomarkers on clinical decision making, diagnosis and health system utilization. In addition to data collection from physicians, the study will engage patients and their care partners in assessing the value of biomarker testing. IMPACT-AD BC investigators hypothesize that testing for CSF biomarkers of Alzheimer's disease in individuals with cognitive impairment, as part of routine clinical care, improves clinical management, diagnostic certainty, diagnostic accuracy, and healthcare resource utilization, and that patients and their care partners find the information valuable in planning for the future.

Description:

The IMPACT-AD BC study is an observational, longitudinal cohort study designed to understand the impact of cerebrospinal fluid (CSF) testing for core Alzheimer's disease biomarkers on clinical decision making, diagnosis, health system utilization, and patients and their care partners.

Dementia specialists from multiple sites in the Canadian province of British Columbia will be approached to provide informed consent to participate. When these physicians order Alzheimer's disease CSF biomarker testing as part of routine care (DeMarco et al 2020), their patients will be eligible to participate in the study. Eligible patients (the patient participants) and their study partners (e.g., a family member or care partner) will be approached to provide informed consent to participate. The dementia specialists will provide diagnosis and management plans for their consenting patient participants before and after Alzheimer's disease CSF biomarker results. One year after release of the Alzheimer's disease CSF biomarker results, dementia specialists complete another questionnaire to assess the stability of their responses. In addition to these data, the study will collect patient participant/care partner perspectives on CSF biomarker testing post-results disclosure.

Via the IMPACT-AD BC study, the investigators will collect the first data of its kind on the utility of CSF biomarkers in routine care in Canada, with the overall goal of improving care and support systems for individuals living with neurodegenerative disorders.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: March 2023
• Est. primary completion date: August 2022
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Participant is either a dementia specialist, or a patient of a consenting dementia specialist;

• Patient participant is age 40 and older;

• Patient participant has a diagnosis verified by a dementia specialist within 24 months of: subjective cognitive decline (Shaw et al., 2018), or mild cognitive impairment or dementia, according to DSM-IV (DSM-IV-TR, 2000) and/or National Institutes of Aging-Alzheimer's Association (Albert et al., 2011; McKhann et al., 2011) criteria;

• The etiologic cause of cognitive impairment is uncertain after a comprehensive evaluation by a dementia specialist, including general medical and neurological examination, mental status testing including standard measures of cognitive impairment, laboratory testing, and structural neuroimaging;

• Cognitive disorder is considered to be on the Alzheimer's continuum, including, but not limited to, mild cognitive impairment with suspected Alzheimer's pathology that does not reach the criteria for dementia;

• Dementia specialist deems that CSF Alzheimer's disease biomarkers are appropriate as per routine clinical care;

• Patient participant consents to a lumbar puncture for CSF analysis as part of clinical care.

Exclusion Criteria:

• Patient participant has normal cognition;

• Patient participant lumbar puncture requires imaging guidance;

• Knowledge of amyloid status, in the opinion of the treating dementia specialist, may cause significant psychological harm or otherwise negatively impact the patient or family;

• Amyloid status already known to patient or dementia specialist based on prior Aß positron emission tomography (PET) imaging or previous CSF analysis;

• Aß and tau CSF biomarkers ordered solely based on a family history of dementia, presence of apolipoprotein E4 genotype, or as a screening test for asymptomatic individuals;

• Aß and tau CSF biomarkers ordered for non-medical purposes (e.g., legal, employment screening, insurance coverage, patient or family member curiosity);

• Current (i.e., active) patient participation in an anti-amyloid or anti-tau therapeutic trial;

• Presence of other significant chronic brain disease in patient (e.g., malignant tumor);

• Patient had symptomatic stroke or transient ischemic attack within the previous 12 months;

• Life expectancy of patient is less than 24 months based on medical co-morbidities;

• Lack of caregiver who can provide corroborative information if the patient participant lacks capacity to do so themselves.

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Cognitive Impairment
• Dementia
• Mild Cognitive Impairment

Intervention

Diagnostic Test:
• Alzheimer's disease CSF biomarkers
Measurement of amyloid beta peptide 1-42, amyloid beta peptide 1-40, and total tau in cerebrospinal fluid.

Locations

Country	Name	City	State
Canada	Northern Health	Prince George	British Columbia
Canada	Providence Health Care	Vancouver	British Columbia
Canada	Vancouver Coastal Health	Vancouver	British Columbia
Canada	Island Health	Victoria	British Columbia

Sponsors (6)

Lead Sponsor	Collaborator
University of British Columbia	Brain Canada, Health Canada, Michael Smith Foundation for Health Research, St. Paul's Foundation, Women's Brain Health Initiative

Country where clinical trial is conducted

Canada, 

References & Publications (6)

Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21. — View Citation

American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV [Internet]. 4th ed. Washington (DC): American Psychiatric Association; 1994 [cited 2010 Mar 8]. 866 p.

DeMarco ML, Nguyen Q, Fok A, Hsiung GR, van der Gugten JG. An automated clinical mass spectrometric method for identification and quantification of variant and wild-type amyloid-ß 1-40 and 1-42 peptides in CSF. Alzheimers Dement (Amst). 2020 Jun 30;12(1):e12036. doi: 10.1002/dad2.12036. eCollection 2020. — View Citation

Johnson KA, Minoshima S, Bohnen NI, Donohoe KJ, Foster NL, Herscovitch P, Karlawish JH, Rowe CC, Hedrick S, Pappas V, Carrillo MC, Hartley DM. Update on appropriate use criteria for amyloid PET imaging: dementia experts, mild cognitive impairment, and education. J Nucl Med. 2013 Jul;54(7):1011-3. doi: 10.2967/jnumed.113.127068. Epub 2013 Jun 10. — View Citation

McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. Epub 2011 Apr 21. — View Citation

Shaw LM, Arias J, Blennow K, Galasko D, Molinuevo JL, Salloway S, Schindler S, Carrillo MC, Hendrix JA, Ross A, Illes J, Ramus C, Fifer S. Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer's disease. Alzheimers Dement. 2018 Nov;14(11):1505-1521. doi: 10.1016/j.jalz.2018.07.220. Epub 2018 Oct 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the impact of Alzheimer's disease core CSF biomarker testing on the management of patients meeting the appropriate use criteria for lumbar puncture and testing.	Determine the percent change between intended management (without biomarkers) and actual patient management (with biomarkers) in a composite measure of at least one of the following: Alzheimer's disease drug therapy; Other relevant drug therapy; Diagnostic procedure, imaging, other biofluid testing; Referral or counselling.	12 months
Primary	To describe the participant's experience with Alzheimer's disease CSF biomarker testing.	Describe the participant's experience with Alzheimer's disease CSF biomarker testing and evaluate the impact of testing on their planning and decision-making via interviews one-month and six-months post-disclosure of CSF biomarker results.	6 months
Primary	To describe the study partner's experience with Alzheimer's disease CSF biomarker testing.	Describe the study partner's experience with Alzheimer's disease CSF biomarker testing and evaluate the impact of testing on their planning and decision-making via interviews one-month and six-months post-disclosure of CSF biomarker results.	6 months
Secondary	To assess changes in participant management among various clinical presentations.	Describe the association of Alzheimer's disease CSF biomarker testing results with changes in management in individuals, from prodromal to dementia stage, presenting with typical clinical presentations of Alzheimer's disease versus atypical clinical presentations of Alzheimer's disease versus non-Alzheimer's neurodegenerative disorders.	12 months
Secondary	To assess changes in participant management by clinical disease stage.	Describe the association of Alzheimer's disease CSF biomarker testing results with changes in management in individuals presenting with mild cognitive symptoms versus dementia.	12 months
Secondary	To assess the impact of Alzheimer's disease core CSF biomarker testing on the change in diagnosis and diagnostic confidence.	Determine the percentage change in diagnosis and physician-rated diagnostic confidence from the pre-biomarker time-point to the post-biomarker time-point.	12 months

External Links

•   IMPACT-AD BC study website