Disclosing Dementia Risk Based on Plasma Phosphorylated Tau

Alzheimer Disease Clinical Trial

Official title:

Disclosing Dementia Risk Based on Plasma Phosphorylated Tau

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05377060
• Other study ID #: 220449
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2022
• Est. completion date: May 31, 2024

Study information

• Verified date: March 2024
• Source: Vanderbilt University Medical Center
• Contact: Corey J Bolton, PsyD
• Phone: 3522355145
• Email: corey.bolton[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Novel blood-based biomarkers of Alzheimer's disease (AD), such as plasma levels of tau phosphorylated at threonine 181 (p-tau181), have shown great promise in detecting early AD pathology. While current studies point to this biomarker as having great clinical utility, one necessary step before clinical implementation is developing safe and effective methods for disclosure of results. Past risk disclosure studies have shown that disclosing risk for AD based on genetics or amyloid status is safe, but these studies have largely focused on cognitively unimpaired individuals. This study seeks to develop comprehensible educational materials to aid risk disclosure and examine the effect of risk disclosure based on plasma p-tau181 results in a group of participants with mild cognitive impairment (MCI) at imminent risk of converting to dementia. First, educational materials will be developed in collaboration with health communication experts and then refined in focus groups made up of individuals with MCI. Educational materials will be analyzed on several key reading and comprehensibility metrics and will include personalized risk estimate based on a well-accepted risk algorithm (Cullen, et al., 2021). Next, these educational materials will be utilized to disclose risk in a randomized controlled trial with an active control arm receiving disclosure based on age, sex, and cognitive status (based on Mini-Mental State Examination), meant to mimic common methods of clinical diagnostic and prognostic decision making, and an intervention arm receiving disclosure based on the above factors plus plasma p-tau181 results. Outcomes will include measures of comprehension and psychological well-being (anxiety, depression, hopelessness, and distress) and will be assessed immediately after risk disclosure and again at six-month follow-up. It is hypothesized that risk disclosure based on plasma p-tau181 is not more psychologically harmful or less comprehensible than disclosure based on demographic factors and MMSE. This pilot study will provide a necessary step towards moving plasma p-tau biomarkers towards safe clinical implementation and will develop educational materials that can be utilized in future studies and clinical practice.

Description:

Novel blood-based biomarkers of Alzheimer's disease (AD), such as plasma levels of tau phosphorylated at threonine 181 (p-tau181), have shown great promise in sensitively and specifically detecting early AD pathology. Plasma p-tau181 has the potential to dramatically reduce the financial strain and patient care burden associated with identifying patients at increased risk of AD-dementia, as well as improve screening for enrollment in clinical trials which require the presence of AD-pathological changes. While current studies point to this biomarker as having great clinical utility, one necessary step before clinical implementation is developing safe and effective methods for disclosure of results. Past risk disclosure studies have shown that disclosing risk for AD based on genetics or amyloid status is safe, but these studies have largely focused on cognitively unimpaired individuals. This study seeks to develop comprehensible educational materials to aid risk disclosure and examine the effect of risk disclosure based on plasma p-tau181 results in a group of participants with mild cognitive impairment (MCI) at imminent risk of converting to dementia. First, educational materials will be developed in collaboration with health communication experts and then refined in focus groups made up of individuals with MCI. Educational materials will be analyzed on several key reading and comprehensibility metrics and will include personalized risk estimate based on a well-accepted risk algorithm (Cullen, et al., 2021). Next, these educational materials will be utilized to disclose risk in a randomized controlled trial with an active control arm receiving disclosure based on age, sex, and cognitive status (based on Mini-Mental State Examination), meant to mimic common methods of clinical diagnostic and prognostic decision making, and an intervention arm receiving disclosure based on the above factors plus plasma p-tau181 results. Outcomes will include measures of comprehension and psychological well-being (anxiety, depression, hopelessness, and distress) and will be assessed immediately after risk disclosure and again at six-month follow-up. It is hypothesized that risk disclosure based on plasma p-tau181 is not more psychologically harmful or less comprehensible than disclosure based on demographic factors and MMSE. This pilot study will provide a necessary step towards moving plasma p-tau biomarkers towards safe clinical implementation and will develop educational materials that can be utilized in future studies and clinical practice.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: May 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

1. Participants recruited will include 62 adults aged 60 and older.

2. Consensus diagnosis of amnestic MCI by Vanderbilt Alzheimer's Disease Research Center (VADRC) clinician panel.

3. Availability of a reliable study partner (reliable is defined as someone who interacts significantly with the participant and is available to participate in study visits in person).

4. English language fluency.

Exclusion Criteria:

1. Individuals who lack decisional capacity to provide informed consent at baseline will not be enrolled in the study.

2. History of major psychiatric illness (e.g., schizophrenia, bipolar), neurological illness (e.g., epilepsy, multiple sclerosis, Parkinson's disease), or head injury with significant loss of consciousness.

3. Presence of acute psychological distress (i.e., Geriatric Depression Scale >10 at screening).

4. Participation in other risk disclosure protocols.

Related Conditions & MeSH terms

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

Intervention

Behavioral:
• Plasma p-tau risk disclosure
Participants will receive an estimated risk for converting to dementia in the next four years based on age, sex, MMSE score, and plasma p-tau results.
• Standard risk disclosure
Participants will receive an estimated risk for converting to dementia in the next four years based on age, sex, and MMSE score.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Geriatric Depression Scale	Questionnaire assessing depression	Immediately following disclosure
Primary	Geriatric Depression Scale - 6-month follow-up	Questionnaire assessing depression	Immediately following disclosure and at 6-month follow-up
Primary	Geriatric Anxiety Scale	Questionnaire assessing anxiety	Immediately following disclosure
Primary	Geriatric Anxiety Scale - 6-month follow-up	Questionnaire assessing anxiety	At 6-month follow-up
Primary	Beck Hopelessness Scale	Questionnaire assessing hopelessness	Immediately following disclosure
Primary	Beck Hopelessness Scale - 6-month follow-up	Questionnaire assessing hopelessness	At 6-month follow-up
Primary	Impact of Events Scale	Questionnaire assessing event-related distress	At 6-month follow-up
Primary	Immediate Comprehension	Semi-structured interview to assess comprehension of disclosure information	Immediately following disclosure
Primary	Long-term Comprehension	Semi-structured interview to assess comprehension of disclosure information	At 6-month follow-up