## Protocol Section
### Identification Module
**NCT ID:** NCT06429215

**Acronym:** SCD-ReCODED

**Brief Title:** REducing the Risk of COgnitive DEcline ad Dementia in Patients With Subjective Cognitive Decline Through an Immersive Virtual Reality and Telemedicine-based Multi-component Intervention: the SCD-ReCODED Study

**Official Title:** Preventing Cognitive Decline and Dementia Through an Innovative Immersive Virtual Reality and Telemedicine-based Multi-component Intervention: a Randomized Controlled Trial

#### Organization Study ID Info
**ID:** PRIN 2022 PNRR P2022E3CZY
#### Organization
**Class:** OTHER
**Full Name:** I.R.C.C.S. Fondazione Santa Lucia
### Status Module
#### Completion Date
**Date:** 2025-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-20

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-10
**Study First Submit QC Date:** 2024-05-20
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** I.R.C.C.S. Fondazione Santa Lucia

#### Responsible Party

**Investigator Affiliation:** I.R.C.C.S. Fondazione Santa Lucia

**Investigator Full Name:** Maria Stefania De Simone

**Investigator Title:** Principal investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** Older adults with subjective cognitive decline (SCD) are at high risk of developing dementia and frequently experience subclinical symptoms (e.g., anxiety, depression) which are themselves associated with dementia and cognitive decline risk. To date, the lack of effective disease-modifying treatments, along with the reliable identification of modifiable lifestyle risk factors (e.g., cognitive activity, dietary habits, physical exercise), have led to growing interest to invest in non-pharmacological interventions that may reduce the prevalence and incidence of dementia and cognitive decline in older adults. In this framework, the aim of this project is to evaluate the efficacy of an Immersive Virtual Reality (IVR) and telemedicine-based multi-component intervention, combining cognitive training and a health and lifestyle education program, for preventing cognitive decline and dementia in at-risk individuals (i.e., SCD). For this purpose, a randomized, double-blinded controlled trial (RCT) will be conducted on seventy-five eligible individuals with SCD, who will be randomly assigned to one of three conditions: (a) multi-component intervention (MC-I), including SCD-tailored cognitive IVR training plus a health and lifestyle education program, (b) cognitive-only intervention (CO-I), including the SCD-tailored cognitive IVR training plus an active control for the education program, and (c) active control intervention (AC-I) for both cognitive training and education program. Intervention will be provided in 20 at-home sessions (4 sessions/week, each lasting about 30 minutes) over a period of 5 weeks. Outcome measures include clinical, neuropsychological, behavioural and neuroimaging data that will be collected before and immediately after intervention in order to detect potentially intervention-induced changes in objective cognitive functioning (primary outcome), subjective cognitive functioning, mood, quality of life and brain connectivity (secondary outcome). Users' compliance with IVR and telemedicine approach will be also evaluated, as well as individuals' factors affecting training efficacy.

### Conditions Module

**Conditions:**

- Subjective Cognitive Decline

**Keywords:**

- Subjective cognitive decline

- Multi-component training

- Non-pharmacological intervention

- Virtual reality

- Telemedicine

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** DOUBLE

**Who Masked:**

- PARTICIPANT

- OUTCOMES_ASSESSOR

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 75

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** VR cognitive training + Psychoeducation program

**Intervention Names:**

- Device: Multi-component Intervention (MC-I): VR Cognitive training and Psychoeducation on health and lifestyle

**Label:** Multi-component Intervention (MC-I)

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** VR Cognitive training + Psychoeducation active control

**Intervention Names:**

- Device: Cognitive-only intervention (CO-I): VR Cognitive training (+ Psychoeducation active control)

**Label:** Cognitive-only intervention (CO-I)

**Type:** ACTIVE_COMPARATOR

#### Arm Group 3

**Description:** VR Cognitive active control + Psychoeducation active control

**Intervention Names:**

- Device: Active control intervention (AC-I): VR Cognitive active control + Psychoeducation active control

**Label:** Active control intervention (AC-I)

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Multi-component Intervention (MC-I)

**Description:** In a period of 5 consecutive weeks, participants will receive:

* an interactive immersive virtual reality cognitive training for 30 minutes, 3 days per week. It consists in different tasks implemented in virtual real-like scenarios of daily living situations that target the following cognitive processes: long-term associative memory, relational binding, spatial pattern separation and pattern completion;
* an interactive immersive virtual reality health and lifestyle education program for 30 minutes, 1 day per week. It consists in 360° videos aimed at advancing awareness and knowledge of the various health conditions associated with an increased risk of cognitive decline and dementia and helping participants to develop a healthier lifestyle.

**Name:** Multi-component Intervention (MC-I): VR Cognitive training and Psychoeducation on health and lifestyle

**Type:** DEVICE

#### Intervention 2

**Arm Group Labels:**

- Cognitive-only intervention (CO-I)

**Description:** In a period of 5 consecutive weeks, participants will receive:

* the interactive immersive virtual reality cognitive training as described in the MC-I condition, for about 30 minutes, 3 days per week;
* an active control of the immersive virtual reality psychoeducation program for 30 minutes, 1 day per week.

**Name:** Cognitive-only intervention (CO-I): VR Cognitive training (+ Psychoeducation active control)

**Type:** DEVICE

#### Intervention 3

**Arm Group Labels:**

- Active control intervention (AC-I)

**Description:** In a period of 5 consecutive weeks, participants will receive:

* an active control of the immersive virtual reality cognitive training (participants will be requested to virtually carry out daily actions, in the same setting as those performed in cognitive immersive VR training, but they will follow prearranged instructions requiring very low cognitive demands) for about 30 minutes, 3 days per week;
* an active control of the immersive virtual reality psychoeducation program for about 30 minutes, 1 day per week.

**Name:** Active control intervention (AC-I): VR Cognitive active control + Psychoeducation active control

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** The Face-Name Associative Memory Exam (short form - FNAME12) is an associative long-term memory task that requires the participant to learn and retrieve 12 novel face-name and face-occupation pairs. It consists of two learning phases, followed by an immediate cued recall and a 30-min delayed recall and recognition trial.

**Measure:** Cognitive functioning (1): change scores on the Face-Name Associative Memory Exam

**Time Frame:** Baseline, post-intervention (around 6 weeks after baseline)

**Description:** The Visual Short-Term Memory Binding Test is a recognition task based on a change detection paradigm for arrays of stimuli presented on a computer screen. Two conditions are investigated, that is, a shape-only condition as the first and a shape-color condition as the second. In both conditions, participants are asked to remember visual arrays of two or three black polygons (in the shape-only condition) or colored polygons (in the shape-color condition) presented for 2 s (study phase).

**Measure:** Cognitive functioning (2): change scores on the Visual Short-Term Memory Binding Test

**Time Frame:** Baseline, post-intervention (around 6 weeks after baseline)

**Description:** The Spatial pattern separation test assesses the ability to differentiate partially overlapping patterns of activation in order to retrieve one pattern as separate from others that are similar. Specifically, it consists of 36 trials, in which the participant is required to learn the location of a grey circle on a sceen; then the participant is required to recognize the position of the previously-learned grey circle with respect to a foil located either to the left or the right of the target.

**Measure:** Cognitive functioning (3): change scores on the Spatial pattern separation test

**Time Frame:** Baseline, post-intervention (around 6 weeks after baseline)

#### Secondary Outcomes

**Description:** The Subjective Memory Complaints Questionnaire assesses the subjective experience of memory decline. It consists of two sections. Part I provides a global evaluation of memory concerns responses to four general questions (4 items); Part II provides an evaluation of memory concerns in daily life (27 items). For each of the 31 items, participants are asked to respond on a 4-point Likert scale (1 = No, it does not happen to me; 2 = Sometimes, but it does not worry me; 3 = Yes and it worries me; 4 = Yes and it constitutes a problemin at least one area ofmy life, e.g., work, family, leisure, relationships). Higher scores are indicative of more serious memory complaints.

**Measure:** Transfer effect on self-perceived cognitive functioning: change scores on the Subjective Memory Complaints Questionnaire

**Time Frame:** Baseline, post-intervention (around 6 weeks after baseline)

**Description:** Connectomics changes after intervention will be investigated between pairs of regions of the whole brain (with particular interest in areas mainly involved in training-related cognitive processes) and in the global and local topological properties of large-scale networks through graph theoretical approach.

**Measure:** Intervention-induced changes in whole-brain functional connectivity

**Time Frame:** Baseline, post-intervention (around 6 weeks after baseline)

**Measure:** Transfer effect on mood (1): change scores on the 30-item Geriatric Depression Scale

**Time Frame:** Baseline, post-intervention (around 6 weeks after baseline)

**Measure:** Transfer effect on mood (2): change scores on the State-Trait Anxiety Inventory

**Time Frame:** Baseline, post-intervention (around 6 weeks after baseline)

**Measure:** Transfer effect on mood (3): change scores on the 18-item Apathy Evaluation Scale

**Time Frame:** Baseline, post-intervention (around 6 weeks after baseline)

**Measure:** Transfer effect on quality of life and health status: Change scores on the Short Form-36 Health Survey

**Time Frame:** Baseline, post-intervention (around 6 weeks after baseline)

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Self-perceived decline in cognition compared to five years ago
* Lack of objective cognitive impairment.

Exclusion Criteria:

* Clinically significant depression and anxiety;
* Psychiatric disorders;
* Unstable medical conditions.
* Severe visual, auditory, verbal or physical impairments interfere with communication, command compliance, and strategy execution
* Dizziness or epilepsy history;

**Healthy Volunteers:** True

**Maximum Age:** 80 Years

**Minimum Age:** 55 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000019965

- Term: Neurocognitive Disorders

- ID: D000001523

- Term: Mental Disorders

- ID: D000003072

- Term: Cognition Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

### Condition Browse Module - Browse Leaves

- ID: M29705

- Name: Cognitive Dysfunction

- Relevance: HIGH

- As Found: Cognitive Decline

- ID: M6904

- Name: Dementia

- Relevance: HIGH

- As Found: Dementia

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M21836

- Name: Neurocognitive Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M6301

- Name: Cognition Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003704

- Term: Dementia

- ID: D000060825

- Term: Cognitive Dysfunction

### Misc Info Module

- Version Holder: 2024-05-31
