Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
NCT number |
NCT04474379 |
Other study ID # |
202007054 |
Secondary ID |
|
Status |
Enrolling by invitation |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
November 29, 2021 |
Est. completion date |
September 1, 2026 |
Study information
Verified date |
May 2024 |
Source |
Washington University School of Medicine |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The investigators will aim enroll participants into our study within 3-6 months after their
parent study visit so the investigators can utilize some key data points (e.g. PD-MCI
diagnosis, rs-fcMRI data) from that study. PD participants will participate in a single-blind
RCT with two treatment arms: process training and strategy training (Fig 4). They will
complete pre-training assessment (Pre), be randomized to treatment arm (1:1 ratio stratified
by sex), and then complete 8 training sessions over an 8-week period. They will return within
1 week for post-training assessment (Post) and then will complete Follow-up (FU) assessments
via web or mailed survey 3 and 6 months after training ends. They will complete a 12mo FU
assessment in person in conjunction with their annual parent study visit. HC participants
will complete prospective memory assessment at one time point coinciding with (or within 3-6
months of) their parent study visit to determine whether any relationships observed between
rs-fcMRI data and prospective memory are specific to PD.
Description:
Parkinson disease (PD) causes cognitive deficits that can impair instrumental activities of
daily living function and quality of life (QOL) even in the absence of dementia. Currently,
there are no treatments to address this pressing burden and, even worse, some medical
treatments for PD can exacerbate cognitive deficits. For these reasons, behavioral
interventions that attenuate the negative functional consequences of cognitive decline in PD
and thus potentially delay the onset of dementia are in high demand. An intervention that
enables people with PD to remember to perform necessary and meaningful daily activities could
improve or maintain their independence, disease self-management, participation in society,
and reduce caregiver burden. The primary goal of this study is to determine the efficacy of
such an intervention. Importantly, in doing so, the investigators will directly address a
critical point of contention in cognitive intervention research: Which approach (process or
strategy training) is the best option for producing functionally-relevant benefits for people
with PD? Additionally, the study team will investigate behavioral and neurobiological
correlates of prospective memory in PD, including individual characteristics that may predict
treatment response. This work will lead to a targeted and tailored biobehavioral intervention
that optimizes function, promotes QOL, and improves the long-term management of a common
chronic neurological condition. It will move the field of rehabilitation forward by providing
valuable theoretical and practical information related to the type of cognitive intervention
approach that is most appropriate for people with PD. This then will stimulate and justify
the channeling of future research efforts and funding toward further development, testing,
dissemination, and implementation of said approach.
Primary Outcomes:
Aim 1. Laboratory prospective memory performance - The Virtual Week test will be administered
to PD participants at Pre and Post to assess near transfer of training objectively (primary
endpoint). It will also be administered to PD participants at 12mo FU to explore long term
training effects (secondary endpoint) and to HC participants at Pre to investigate neural
mechanisms of prospective memory performance (Aim 3). It is a computerized board game that
simulates daily life and real-world prospective memory challenges. Each circuit represents
one day in which the participant completes time-appropriate activities and makes choices
about them. Embedded in each day are 8 prospective memory tasks (4 event, 4 time).
Participants complete a practice day and then 4 test days; equivalent versions are
counterbalanced across testing sessions. The main outcome variable is prospective memory
accuracy, defined as the proportion of correct prospective memory responses (32 total: 16
event, 16 time). To further explore the effects of time-based training, the investigators
will record strategic clock-checking behavior by requiring participants to click a button to
reveal the virtual time of day.
Aim 2. Reported everyday prospective memory: (2a) General everyday prospective memory
function - The Prospective and Retrospective Memory Questionnaire (PRMQ)will be administered
via web-based or mailed survey to PD participants and informants at Pre, Post and 3mo FU to
assess far transfer of training (primary endpoint), to PD participants and informants at 6mo
and 12mo FU to explore long term training effects (secondary endpoint), and to HC
participants at Pre to determine neural mechanisms of everyday prospective memory (Aim 3).
The PRMQ is the most widely used questionnaire for everyday prospective memory. Participants
rate the frequency of 8 everyday prospective memory failures (1=Never, 5=Very Often), item
scores are summed, and higher scores indicate worse everyday prospective memory. The PRMQ
includes environment- and self-cued subscales (4 items each) that parallel the event- and
time-based task distinction, respectively. (2b) Personalized real-life prospective memory
tasks - The Bangor Goal-Setting Interview (BGSI)offers a standardized means of eliciting
individual goals and rating goal attainment over time and has been successfully used in
cognitive rehabilitation RCTs with older adults, including those with mild to moderate
dementia. During the first two training sessions, after an explanation of the prospective
memory task types (session 1: event, session 2: time), participants will complete the BGSI
with the trainer to identify and set goals for 3-6 real-life prospective memory tasks they
anticipate having to complete over the training period. They and their informants will rate
their Pre and Post attainment of these goals on a 10-point scale (1=never remember to do;
10=always remember to do). Goal attainment ratings are averaged to yield mean attainment
scores.
Additional measures:
Aims 3 & 4. Neural correlates of prospective memory and treatment response - Rs-fcMRI data
will be collected and managed under the auspices of the parent study at Pre. Briefly, MRIs
will be completed OFF PD medications on a 3T Siemens Prisma scanner with a 20 channel head
coil and include up to 6 BOLD rs-fcMRI scans (416 volumes/run, TE=26.6ms, TR=800ms, FOV=
213mm, flip angle=61°, 3mm3 voxels; multiband factor=4; 5:39min) during fixation (eyes open).
More details, including rigorous quality control methods, are in references. The
investigators will use a network-level analysis approach using standard nodes from canonical
networks. Our primary variables of interest will be intranetwork integrity scores, calculated
based on the cross-correlations of each node within the network, for the following cognitive
networks: DMN, CON, FPN, PMN, and MTL. Alternate approaches may include seed-based analyses
(e.g. DLPFC) and Object Oriented Data Analysis followed by post-hoc identification of
significant networks.
Aim 4. Behavioral predictors of treatment response - Based on our pilot RCT (Prelim Data 2)1,
The investigators will administer the Credibility and Expectancy Questionnaire (CEQ) and Beck
Depression Inventory-II (BDI-II) at Pre as potential motivational predictors of treatment
response. The CEQ will be administered at the end of training session 2, so participants have
some knowledge of the intervention on which to base their perceptions of credibility and
expectancy. The investigators will utilize the extensive neuropsychological data collected at
Pre in the parent study to assess potential cognitive predictors of treatment response. Our
primary cognitive variables will be the domain z-scores for Memory and Executive Function,
computed as the average of standardized scores from measures assessing that domain. Other -
PD (and normal cognition for HCs) will be determined via MDS Level II diagnostic criteria in
the parent study based on a comprehensive neuropsychological assessment battery and in-depth
clinical interviews (CDR). In addition to the main measures of interest described above, the
investigators will collect other data to characterize participants, as covariates, or as
secondary outcomes (Table 3). This will permit exploration of the influence of sex or other
relevant biological variables (e.g. co-morbidities, medication) and broader functional
outcomes. The investigators will obtain much of this data from the parent study.