Long-Term Memory DeclineLABYRNCT04253587
Wayfinding Intervention in High-Fidelity Long-Term Memory
A study testing LabyrinthVR, Coherence and Tablet in people with Long-Term Memory Decline and Mild Cognitive Impairment, run by University of California, San Francisco at 1 site in United States.
Trial summary
Therapeutic treatment is yet available for declining memory, which is an impairment affecting the quality of life for many older adults and patients with cognitive impairment. Cognitive training with an immersive video game promises to drive hippocampal-cortical plasticity and associated gains that can restore memory… Read more about this study
- Who is it for?
- Ages 62 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Long-Term Memory Decline, Mild Cognitive Impairment
- What is being tested?
- LabyrinthVR, Coherence and Tablet
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2019to 15 Dec 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 62 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- fluent speakers of English
- completed 12 or more years of education
- normal or corrected-to-normal vision
- dexterity to comfortably operate the scanner-compatible response box
- freedom from physical and neurological conditions contra-indicated for fMRI
- must confirm physical stamina and comfort for 45-minute, brisk walks on level ground
Who cannot join
- use of psychotropic medications
- history of concussions or dizziness, vestibular or balance problems
- significant discomfort with virtual reality experiences
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cognitive Intervention to Restore Capabilities for Learning and Retrieval of High-Fidelity Memory
Therapeutic treatment is yet available for declining memory, which is an impairment affecting the quality of life for many older adults and patients with cognitive impairment. Cognitive training with an immersive video game promises to drive hippocampal-cortical plasticity and associated gains that can restore memory capability or provide therapeutic treatment for memory deficits.
Read the detailed description
A hallmark of higher cognition is the capability for flexible association of diverse bits of information stored in memory, such that experiences can be remembered in detailed and distinct terms (i.e., high-fidelity long-term memory (LTM)). Interventions capable of sustaining improved learning and flexible association of new information into LTM remain elusive. Interventions have yet to be developed to attenuate the decline of high-fidelity LTM in normal aging or provide therapeutic treatment for patients with cognitive impairment without dementia (i.e., MCI).
This project applies a translational neuroscience approach in development of a cognitive training intervention that targets sustained improvement in capabilities for LTM and cognitive control. Treatments use commercially available head-mounted display Virtual Reality (VR) technology and tablet computers to present a deeply immersive spatial wayfinding video game. Based on preliminary results, the hypothesis is that immersion in a game to navigate errands through unfamiliar, visually complex neighborhoods (i.e., wayfinding) will be an effective means to environmental enrichment, which refers to a process whereby new and complex experiences bring change to brain and behavior.
The significance of this platform is from the effects in brain and behavior arising from cognitive training, which can generalize to improvements in untrained capability for high-fidelity LTM. Research in rodents and humans shows that learning a new, enriched environment spurs the healthy function of the hippocampus and supports lifelong neurogenesis. Adult-borne hippocampal neurogenesis has been linked as the neurobiological basis for the formation of new, high-fidelity memories.
The Labyrinth spatial wayfinding game was developed in-house to incorporate full scientific rigor, as with procedures in any properly controlled behavioral experiment. The game uses 3D and 2.5D computer graphics tools, as well as numerous levels of adaptive challenge, to deliver a dynamic, engaging experience for participants throughout the training regimen. Training can be administered with and without participant ambulation in movement through wayfinding runs.
A participant's pre- and post-training assessments will occur promptly before and after their 15 to 20-hour training regimen, including collection of functional MRI (fMRI) and structural MRI data. Cognitive outcome measures will assess capabilities for high-fidelity LTM retrieval.
The a priori hypothesis is that effectiveness of the wayfinding game intervention would be evidenced by post-training improvements in retrieval of high-fidelity LTM and associated cognitive control capabilities. FMRI results associated with the measured cognitive improvements will localize changes in functional brain networks that support gains in memory capabilities. Structural MRI measures will assess morphometric and volumetric changes from pre- to post-training assessments.
- Being tested
- LabyrinthVR, Placebo Games, Coherence, Tablet
- Keywords
- amnestic MCI without dementia, cognitive training
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LabyrinthVRDevice
Head-mounted display virtual reality game designed to induce environmental enrichment in an adaptive, immersive regimen of wayfinding in novel urban and village neighborhoods.
Placebo GamesDevice
Commercially-available, narrative computer games marketed as cognitively enriching.
CoherenceDevice
Head-mounted display virtual reality game designed to present an adaptive rhythm training routine.
TabletDevice
Tablet computer playing Labyrinth VR game but in 2.5D
| Study group | Role | What they receive |
|---|---|---|
| LabyrinthVR Trackers | Experimental | Multi-session cognitive intervention with head-mounted display virtual reality computer game that presents an adaptive spatial wayfinding challenge. Game movement via participant ambulation wearing leg-position trackers. Receives: Device: LabyrinthVR |
| LabyrinthVR Scoot | Experimental | Multi-session cognitive intervention with head-mounted display virtual reality computer game that presents an adaptive spatial wayfinding challenge. Game movement via teleporting technique. Receives: Device: LabyrinthVR |
| Placebo Controls | Placebo comparator | Multi-session cognitive intervention with handheld tablet or wireless virtual reality headset presentation of commercially available, narrative computer games. Receives: Device: Placebo Games |
| Coherence | Active comparator | Multi-session cognitive intervention with head-mounted display virtual reality computer game that presents an adaptive rhythm training game. Receives: Device: Coherence |
| Labyrinth Tablet | Experimental | Multi-session cognitive intervention with tablet computer, displaying 2.5D version of Labyrinth game in an adaptive spatial wayfinding challenge. Game movement via on-screen control buttons. Receives: Device: Tablet |
| Labyrinth VR wireless | Experimental | Multi-session cognitive intervention with head-mounted display virtual reality computer game using wireless, narrower filed technology to presents an adaptive spatial wayfinding challenge. Game movement via teleporting technique. Receives: Device: LabyrinthVR |
What is being measured
The primary outcome is the main question the study is designed to answer.
MDT Change in Mnemonic Discrimination
Mnemonic discrimination task testing recognition memory for common objects, as reported in scores on a scale of the Lure Discrimination Index ranging from 0.00 to 1.00 where higher values show better performance.
Measured: baseline immediately before and post-assessment immediately after training regimen is completed
WALK Change in Recall
Encoding and test of recent autobiographical long-term memory, as reported in scores on a scale of Percentage of Items Recalled ranging from 0.00 to 1.00 where higher values show better performance.
Measured: baseline immediately before and post-assessment immediately after training regimen is completed
Changes in Volumetric-based Brain Morphometry Associated With Training-induced Changes in Mnemonic Discrimination
Structural MRI T1 data will be analyzed in terms of volumetric-based morphometry and compared between treatment arms and timepoints.
Measured: during collection of Outcome 1, baseline immediately before and post-assessment immediately after training regimen is completed
Changes in Task-based Cortical Functional Connectivity Associated With Training-induced Changes in Mnemonic Discrimination
functional MRI data will be analyzed in terms of beta-series correlations between co-active cortical regions of interest and compared between treatment arms and timepoints.
Measured: during collection of Outcome 1, baseline immediately before and post-assessment immediately after training regimen is completed
Secondary outcomes (2)
Remote Cognitive Module (RCM)
A tablet application using a speech-to-text interface to administer neuropsychological tests comparable to CVLT-II verbal memory, verbal fluency, digit span and Trail Making Test-B.
Raw scores from the tasks will be transformed to z-scores, relative to population normative values, and a participant's z-scores will be the uniform measures of their performance across RCM tasks.
THESE DATA WERE NOT COLLECTED OR ANALYZED DUE TO FUNDING CONSTRAINTS
Measured: baseline immediately before and post-assessment immediately after training regimen is completed
Test of Visual Attention Change in Top-down Control
test of speed and accuracy of visual attention and impulsivity
Measured: baseline immediately before and post-assessment immediately after training regimen is completed
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start1 Oct 2019
- Primary completion15 Dec 2021
- Study completion15 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Long-Term Memory DeclineStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter E Wais, PhD, Principal investigator, Neuroscape, Department of Neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04253587
- Sponsor's protocol ID
- 19-27586-A
- Acronym
- LABYR
- Status last verified
- Feb 2023
- First submitted
- 29 Jan 2020
- Last updated
- 27 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Wais PE, Arioli M, Anguera-Singla R, Gazzaley A. Virtual reality video game improves high-fidelity memory in older adults. Sci Rep. 2021 Jan 28;11(1):2552. doi: 10.1038/s41598-021-82109-3.
PubMed 33510315
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cognitive Intervention to Restore Capabilities for Learning and Retrieval of High-Fidelity Memory
- ClinicalTrials.gov ID
- NCT04253587
- Acronym / sponsor ID
- LABYR / 19-27586-A
- Keywords
- amnestic MCI without dementia, cognitive training
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 15 Dec 2021 (actual)
- Study completion
- 15 Dec 2021 (actual)
- First posted
- 5 Feb 2020 (actual)
- Results
- Posted 27 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Therapeutic treatment is yet available for declining memory, which is an impairment affecting the quality of life for many older adults and patients with cognitive impairment. Cognitive training with an immersive video game promises to drive hippocampal-cortical plasticity and associated gains that can restore memory capability or provide therapeutic treatment for memory deficits.
Detailed description
A hallmark of higher cognition is the capability for flexible association of diverse bits of information stored in memory, such that experiences can be remembered in detailed and distinct terms (i.e., high-fidelity long-term memory (LTM)). Interventions capable of sustaining improved learning and flexible association of new information into LTM remain elusive. Interventions have yet to be developed to attenuate the decline of high-fidelity LTM in normal aging or provide therapeutic treatment for patients with cognitive impairment without dementia (i.e., MCI).
This project applies a translational neuroscience approach in development of a cognitive training intervention that targets sustained improvement in capabilities for LTM and cognitive control. Treatments use commercially available head-mounted display Virtual Reality (VR) technology and tablet computers to present a deeply immersive spatial wayfinding video game. Based on preliminary results, the hypothesis is that immersion in a game to navigate errands through unfamiliar, visually complex neighborhoods (i.e., wayfinding) will be an effective means to environmental enrichment, which refers to a process whereby new and complex experiences bring change to brain and behavior.
The significance of this platform is from the effects in brain and behavior arising from cognitive training, which can generalize to improvements in untrained capability for high-fidelity LTM. Research in rodents and humans shows that learning a new, enriched environment spurs the healthy function of the hippocampus and supports lifelong neurogenesis. Adult-borne hippocampal neurogenesis has been linked as the neurobiological basis for the formation of new, high-fidelity memories.
The Labyrinth spatial wayfinding game was developed in-house to incorporate full scientific rigor, as with procedures in any properly controlled behavioral experiment. The game uses 3D and 2.5D computer graphics tools, as well as numerous levels of adaptive challenge, to deliver a dynamic, engaging experience for participants throughout the training regimen. Training can be administered with and without participant ambulation in movement through wayfinding runs.
A participant's pre- and post-training assessments will occur promptly before and after their 15 to 20-hour training regimen, including collection of functional MRI (fMRI) and structural MRI data. Cognitive outcome measures will assess capabilities for high-fidelity LTM retrieval.
The a priori hypothesis is that effectiveness of the wayfinding game intervention would be evidenced by post-training improvements in retrieval of high-fidelity LTM and associated cognitive control capabilities. FMRI results associated with the measured cognitive improvements will localize changes in functional brain networks that support gains in memory capabilities. Structural MRI measures will assess morphometric and volumetric changes from pre- to post-training assessments.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| LabyrinthVR Trackers | Experimental | Device: LabyrinthVRMulti-session cognitive intervention with head-mounted display virtual reality computer game that presents an adaptive spatial wayfinding challenge. Game movement via participant ambulation wearing leg-position trackers. |
| LabyrinthVR Scoot | Experimental | Device: LabyrinthVRMulti-session cognitive intervention with head-mounted display virtual reality computer game that presents an adaptive spatial wayfinding challenge. Game movement via teleporting technique. |
| Placebo Controls | Placebo comparator | Device: Placebo GamesMulti-session cognitive intervention with handheld tablet or wireless virtual reality headset presentation of commercially available, narrative computer games. |
| Coherence | Active comparator | Device: CoherenceMulti-session cognitive intervention with head-mounted display virtual reality computer game that presents an adaptive rhythm training game. |
| Labyrinth Tablet | Experimental | Device: TabletMulti-session cognitive intervention with tablet computer, displaying 2.5D version of Labyrinth game in an adaptive spatial wayfinding challenge. Game movement via on-screen control buttons. |
| Labyrinth VR wireless | Experimental | Device: LabyrinthVRMulti-session cognitive intervention with head-mounted display virtual reality computer game using wireless, narrower filed technology to presents an adaptive spatial wayfinding challenge. Game movement via teleporting technique. |
Who may qualify
- Ages
- 62 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- fluent speakers of English
- completed 12 or more years of education
- normal or corrected-to-normal vision
- dexterity to comfortably operate the scanner-compatible response box
- freedom from physical and neurological conditions contra-indicated for fMRI
Key exclusion criteria (3 listed)
- use of psychotropic medications
- history of concussions or dizziness, vestibular or balance problems
- significant discomfort with virtual reality experiences
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LabyrinthVRHead-mounted display virtual reality game designed to induce environmental enrichment in an adaptive, immersive regimen of wayfinding in novel urban and village neighborhoods. | Device | Labyrinth VR wireless, LabyrinthVR Scoot, LabyrinthVR Trackers |
| Placebo GamesCommercially-available, narrative computer games marketed as cognitively enriching. | Device | Placebo Controls |
| CoherenceHead-mounted display virtual reality game designed to present an adaptive rhythm training routine. | Device | Coherence |
| TabletTablet computer playing Labyrinth VR game but in 2.5D | Device | Labyrinth Tablet |
Primary outcome
MDT Change in Mnemonic Discrimination
Time frame: baseline immediately before and post-assessment immediately after training regimen is completed
Mnemonic discrimination task testing recognition memory for common objects, as reported in scores on a scale of the Lure Discrimination Index ranging from 0.00 to 1.00 where higher values show better performance.
WALK Change in Recall
Time frame: baseline immediately before and post-assessment immediately after training regimen is completed
Encoding and test of recent autobiographical long-term memory, as reported in scores on a scale of Percentage of Items Recalled ranging from 0.00 to 1.00 where higher values show better performance.
Changes in Volumetric-based Brain Morphometry Associated With Training-induced Changes in Mnemonic Discrimination
Time frame: during collection of Outcome 1, baseline immediately before and post-assessment immediately after training regimen is completed
Structural MRI T1 data will be analyzed in terms of volumetric-based morphometry and compared between treatment arms and timepoints.
Changes in Task-based Cortical Functional Connectivity Associated With Training-induced Changes in Mnemonic Discrimination
Time frame: during collection of Outcome 1, baseline immediately before and post-assessment immediately after training regimen is completed
functional MRI data will be analyzed in terms of beta-series correlations between co-active cortical regions of interest and compared between treatment arms and timepoints.
2 secondary outcomes
Remote Cognitive Module (RCM)
Time frame: baseline immediately before and post-assessment immediately after training regimen is completed
Test of Visual Attention Change in Top-down Control
Time frame: baseline immediately before and post-assessment immediately after training regimen is completed
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 33510315Wais PE, Arioli M, Anguera-Singla R, Gazzaley A. Virtual reality video game improves high-fidelity memory in older adults. Sci Rep. 2021 Jan 28;11(1):2552. doi: 10.1038/s41598-021-82109-3.
- Individual participant dataSharing planned: No
Related trials for Long-Term Memory Decline
Recruiting
Wayfinding Intervention and Long-Term Memory
Long-Term Memory Decline, Mild Cognitive Impairment
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter E Wais, PhD principal investigator
Neuroscape, Department of Neurology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing LabyrinthVR, Coherence and Tablet in people with Long-Term Memory Decline and Mild Cognitive Impairment, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MDT Change in Mnemonic Discrimination (time frame: baseline immediately before and post-assessment immediately after training regimen is completed). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04253587, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2023.