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

Primary Purpose

Alzheimer Disease

Status
Unknown status
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Cognitive Stimulation (CS)
Sponsored by
University of Roma La Sapienza
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease focused on measuring Alzheimer's Disease, Mild Cognitive Stimulation, Non Pharmacological Intervention, Cognitive Stimulation, Transcranial Magnetic Stimulation, Blink Reflex, Neuropsychological Evaluation, Randomized Controlled Trial

Eligibility Criteria

60 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Department of Human Neuroscience, Sapienza University of RomeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

No Intervention

No Intervention

No Intervention

Arm Label

moderate AD-experimental

mild AD-experimental

MCI-experimental

moderate AD-placebo

mild AD-placebo

MCI-placebo

Arm Description

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.

Experimental Intervention: the same of the "moderate AD-experimental" arm

Experimental Intervention: the same of the "moderate AD-experimental" arm

Outcomes

Primary Outcome Measures

Change in global cognition as assessed by Mini Mental State Examination
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.
Change in dementia severity as assessed by Clinical Dementia Rating Scale
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.

Secondary Outcome Measures

Change in frontal functions as assessed by Frontal Assessment Battery
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.
Change in verbal memory as assessed by Rey Auditory Verbal Learning Test
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.
Change in attention as assessed by Visual Search Test
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.
Change in visuospatial functions as assessed by Clock Drawing Test
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.
Change in naming as assessed by Boston Naming Test
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.
Change in synaptic plasticity as assessed by Paired Associative Stimulation
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%.
Change in blinking as assessed by Blink Rate Evaluation
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.

Full Information

First Posted
November 26, 2018
Last Updated
December 20, 2018
Sponsor
University of Roma La Sapienza
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1. Study Identification

Unique Protocol Identification Number
NCT03784183
Brief Title
Neuropsychological and Neurophysiological Effects of Cognitive Stimulation in Patients With Alzheimer's Disease and Mild Cognitive Impairment
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
November 2018
Overall Recruitment Status
Unknown status
Study Start Date
September 27, 2018 (Actual)
Primary Completion Date
October 1, 2020 (Anticipated)
Study Completion Date
October 1, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Roma La Sapienza

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
Keywords
Alzheimer's Disease, Mild Cognitive Stimulation, Non Pharmacological Intervention, Cognitive Stimulation, Transcranial Magnetic Stimulation, Blink Reflex, Neuropsychological Evaluation, Randomized Controlled Trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
A Randomized, Single-Blind, Placebo-Controlled, Parallel-Group
Masking
Outcomes Assessor
Masking Description
Single Blind: Neuropsychologists and Neurophysiologists are prevented from having knowledge of the intervention assigned to the participants.
Allocation
Randomized
Enrollment
126 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
moderate AD-experimental
Arm Type
Experimental
Arm Description
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.
Arm Title
mild AD-experimental
Arm Type
Experimental
Arm Description
Experimental Intervention: the same of the "moderate AD-experimental" arm
Arm Title
MCI-experimental
Arm Type
Experimental
Arm Description
Experimental Intervention: the same of the "moderate AD-experimental" arm
Arm Title
moderate AD-placebo
Arm Type
No Intervention
Arm Title
mild AD-placebo
Arm Type
No Intervention
Arm Title
MCI-placebo
Arm Type
No Intervention
Intervention Type
Other
Intervention Name(s)
Cognitive Stimulation (CS)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in global cognition as assessed by Mini Mental State Examination
Description
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.
Time Frame
24 and 48 weeks
Title
Change in dementia severity as assessed by Clinical Dementia Rating Scale
Description
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.
Time Frame
24 and 48 weeks
Secondary Outcome Measure Information:
Title
Change in frontal functions as assessed by Frontal Assessment Battery
Description
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.
Time Frame
24 and 48 weeks
Title
Change in verbal memory as assessed by Rey Auditory Verbal Learning Test
Description
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.
Time Frame
24 and 48 weeks
Title
Change in attention as assessed by Visual Search Test
Description
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.
Time Frame
24 and 48 weeks
Title
Change in visuospatial functions as assessed by Clock Drawing Test
Description
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.
Time Frame
24 and 48 weeks
Title
Change in naming as assessed by Boston Naming Test
Description
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.
Time Frame
24 and 48 weeks
Title
Change in synaptic plasticity as assessed by Paired Associative Stimulation
Description
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%.
Time Frame
24 and 48 weeks
Title
Change in blinking as assessed by Blink Rate Evaluation
Description
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.
Time Frame
24 and 48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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 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.
Facility Information:
Facility Name
Department of Human Neuroscience, Sapienza University of Rome
City
Rome
ZIP/Postal Code
00185
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carlo de Lena, MD
Phone
0649914028
Ext
0039
Email
carlo.delena@uniroma1.it
First Name & Middle Initial & Last Name & Degree
Alessandro Trebbastoni, MD, PhD
Phone
3491496146
Ext
0039
Email
alessandro.trebbastoni@uniroma1.it

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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