Neuropsychological and Neurophysiological Effects of Cognitive Stimulation in Patients With Alzheimer's Disease and Mild Cognitive Impairment

December 20, 2018 updated by: Carlo de Lena, University of Roma La Sapienza

A Randomized, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy of a Non-Pharmacological Intervention of Cognitive Stimulation in Subjects With Alzheimer's Disease and Mild Cognitive Impairment: The Brain Stimulation Project.

The present study aims to evaluate the effect of cognitive stimulation (CS) in participants with a diagnosis of moderate and mild Alzheimer's disease (AD) and mild cognitive impairment (MCI) compared to control subjects not receiving any non-pharmacological interventions. Treated participants will receive a structured CS consisting of a wide range of activities aimed at the general improvement of social functioning and the maintenance of cognitive functions. The study consists of a 24-week treatment phase and a follow-up period of 24 weeks. During the treatment period, patients will receive two CS sessions a week. At baseline, all the participants undergo an extensive neuropsychological evaluation and a neurophysiological assessment aimed at studying the frequency of spontaneous blinking (blink rate) and cortical excitability and synaptic plasticity by means of the transcranial magnetic stimulation (TMS). Neuropsychological and neurophysiological evaluations will be repeated at the end of the treatment (week 24) and at the end of the follow-up period (week 48) in order to evaluate short- and long-term effects of CS. The hypothesis of this research is that CS may improve cognition and the neurophysiological parameters studied in treated participants compared to those untreated.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
126

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

60 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. moderate AD participants

    • Clinical diagnosis of probable AD (National Institute on Aging and Alzheimer's Association criteria)
    • 1 < Clinical Dementia Rating Scale < 3
    • 13 ≤ Mini-Mental State Examination < 20/30
    • Modified Hachinski Ischaemic Scale (MHIS) ≤ 4
    • Geriatric Depression Scale (GDS) ≤ 6

  2. mild AD participants

    • Clinical diagnosis of probable AD (National Institute on Aging and Alzheimer's Association criteria)
    • Clinical Dementia Rating Scale = 1 (memory box score ≥ 0.5)
    • 20 > Mini-Mental State Examination < 27/30
    • Modified Hachinski Ischaemic Scale (MHIS) ≤ 4
    • Geriatric Depression Scale (GDS) ≤ 6

  3. MCI participants

    • Clinical diagnosis of probable AD (National Institute on Aging and Alzheimer's Association criteria)
    • Clinical Dementia Rating Scale < 1 (memory box score ≥ 0.5)
    • Mini-Mental State Examination ≥ 24/30
    • Modified Hachinski Ischaemic Scale (MHIS) ≤ 4
    • Geriatric Depression Scale (GDS) ≤ 6

Exclusion Criteria for all the participants (moderate AD, mild AD and MCI):

  • Any medical or neurological condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause of the subject's cognitive impairment.
  • Clinically significant psychiatric illness (e.g., uncontrolled major depression, bipolar affective disorder) within 6 months prior to the enrolment.
  • Any medications that, in the opinion of the Investigator, may contribute to cognitive impairment or impair the subject's ability to perform cognitive testing or complete study procedures.
  • Contraindications to Transcranial Magnetic Stimulation (history of epilepsy or seizures/presence of pacemaker).
  • Subject currently living in an organized care facility with extensive intervention and/or support of daily living activities.
  • Inability to comply with study requirements and commitments
  • Has not one informant/care partner who, in the Investigator's opinion, has frequent and sufficient contact with the subject as to be able to provide accurate information about the subject's cognitive and functional abilities.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: moderate AD-experimental
Experimental Intervention: The CS shall be carried out in groups (5-7 participants), twice a week. Each session lasts 90 minutes. CS sessions begin with a training for temporal and spatial orientation in which participants are asked to recognize and recall the date and the place with the help of some environmental aids (calendars, clocks, pictures and maps). Then the participants complete an array of cognitive tasks for memory, attention, language, visuo-spatial functions and executive functions. These tasks range from individual paper-and-pencil exercises to verbal-learning exercises that have to be solved by the group.
Other: Cognitive Stimulation (CS)
CS consists of a wide range of structured activities aimed at the general improvement of social functioning and the maintenance of different cognitive functions. It is a non-specific in-group approach that places particular emphasis on social interactions.
Experimental: mild AD-experimental
Experimental Intervention: the same of the "moderate AD-experimental" arm
Other: Cognitive Stimulation (CS)
CS consists of a wide range of structured activities aimed at the general improvement of social functioning and the maintenance of different cognitive functions. It is a non-specific in-group approach that places particular emphasis on social interactions.
Experimental: MCI-experimental
Experimental Intervention: the same of the "moderate AD-experimental" arm
Other: Cognitive Stimulation (CS)
CS consists of a wide range of structured activities aimed at the general improvement of social functioning and the maintenance of different cognitive functions. It is a non-specific in-group approach that places particular emphasis on social interactions.
No Intervention: moderate AD-placebo
No Intervention: mild AD-placebo
No Intervention: MCI-placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in global cognition as assessed by Mini Mental State Examination
Time Frame: 24 and 48 weeks
Change from baseline in Mini Mental State Examination score at Week 24 and 48. This scale investigates global cognition. Scale range: 0-30. Normal values >24. Higher values represent a better outcome.
24 and 48 weeks
Change in dementia severity as assessed by Clinical Dementia Rating Scale
Time Frame: 24 and 48 weeks
Change from baseline in Clinical Dementia Rating Scale score at Week 24 and 48. This scale investigates global cognition and dementia severity. Scale range: 0-5. Normal values = 0. Higher values represent a worse outcome.
24 and 48 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in frontal functions as assessed by Frontal Assessment Battery
Time Frame: 24 and 48 weeks
Change from baseline in Frontal Assessment Battery scores at Week 24 and 48. This scale investigates the executive functions. Scale range: 0-30. Normal values ≥ 13.5. Higher values represent a better outcome.
24 and 48 weeks
Change in verbal memory as assessed by Rey Auditory Verbal Learning Test
Time Frame: 24 and 48 weeks
Change from baseline in Rey Auditory Verbal Learning Test scores at Week 24 and 48. This test investigates verbal learning and memory. Immediate recall scale range: 0-75. Normal values >28.52. Delayed recall scale range: 0-15. Normal values >4.68. Higher values represent a better outcome.
24 and 48 weeks
Change in attention as assessed by Visual Search Test
Time Frame: 24 and 48 weeks
Change from baseline in Visual Search test score at Week 24 and 48. This test investigates selective attention. Scale range: 0-60. Normal values >30. Higher values represent a better outcome.
24 and 48 weeks
Change in visuospatial functions as assessed by Clock Drawing Test
Time Frame: 24 and 48 weeks
Change from baseline in Clock Drawing Test score at Week 24 and 48. This test investigates visuospatial abilities and executive functioning. Scale range: 0-61. Normal values >42.17. Higher values represent a better outcome.
24 and 48 weeks
Change in naming as assessed by Boston Naming Test
Time Frame: 24 and 48 weeks
Change from baseline in Boston Naming test score at Week 24 and 48. This test measure object naming from line drawings. Scale range: 0-60. Normal values >24. Higher values represent a better outcome.
24 and 48 weeks
Change in synaptic plasticity as assessed by Paired Associative Stimulation
Time Frame: 24 and 48 weeks
Change from baseline in Paired Associative Stimulation at Week 24 and 48. Paired associative stimulation is a paradigm combining peripheral nerve stimulation and transcranial magnetic stimulation over the contralateral primary motor cortex. In healthy humans, Paired Associative Stimulation after-effects last about 30-60 minutes. The extent of facilitatory-Paired Associative Stimulation-induced effects on MEP amplitude ranges from 120% to 160%, while inhibitory-Paired Associative Stimulation may induce a reduction of muscle-evoked potential amplitude that ranges from 60% to 90%.
24 and 48 weeks
Change in blinking as assessed by Blink Rate Evaluation
Time Frame: 24 and 48 weeks
Change from baseline in the blink rate at Week 24 and 48. Spontaneous blinking was measured by the Blink Rate and was expressed as number of blinks per minute. Normal values: mean Blink Reflex value at rest is 17 blinks/minute; during conversation is 26 blinks/minute; during reading is 4.5 blinks/minute. Cut offs: not applicable.
24 and 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Roma La Sapienza

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 27, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 26, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 20, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 21, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 21, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 20, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BSP-2018

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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