TMS Treatment of Social Cognition Skills in Mild Cognitive Impairment
Primary Purpose
Mild Cognitive Impairment
Status
Recruiting
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
rTMS treatment
Sponsored by
About this trial
This is an interventional treatment trial for Mild Cognitive Impairment focused on measuring ripetitive transcranial magnetic stimulation treatment, social cognition, theory of mind, empathy, social perception, social behavior
Eligibility Criteria
Inclusion Criteria:
- Subjects aged 50 to 85 years old, inclusive, at the time of informed consent;
- Must have at least 5 years of education or work experience to exclude mental deficits other than MCI;
- Must meet Petersen's criteria for mild cognitive impairment, and must have:
- Clinical dementia rating global score of 0.5;
- Mini-Mental State Examination score between 24 and 30;
- Must have a score ≥ 26.5 at Token test to ensure that subjects have the ability to understand the instructions and procedures;
- Must have a score < 29 at Beck Depression Inventory to exclude major depression that could compromise the patient's ability to engage in the study;
- Apart from a clinical diagnosis of MCI, the subject must be in good health;
- Must be on stable dose of antidepressant (if applicable) for at least 2 months prior to the enrolment.
Exclusion Criteria:
- Any uncontrolled medical or neurological/neurodegenerative condition (other than MCI);
- Clinical significant unstable psychiatric illness requiring treatment with neuroleptic;
- Transient ischemic attack, stroke, or any unexplained loss of consciousness or severe ongoing stressor within 1 year prior to screening;
- History of seizure within10 years prior to screening;
- Recent history of alcohol or substance abuse or use of cannabinoids;
- Any other medical conditions that are not stable or controlled, or could affect the subject's safety or interfere with the study assessments and treatment;
- Contraindication to having TMS treatment;
- Inability to understand the purpose of the study or to comply with study requirements.
Sites / Locations
- Neurocentro della Svizzera italiana,Ospedale Regionale di LuganoRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
RR-GR
SR-GR
Arm Description
MCI patients with social cognition deficits will receive 4 weeks of rTMS stimulation
MCI patients with social cognition deficits will receive 2 weeks of placebo treatment, followed by 2 weeks of real rTMS stimulation
Outcomes
Primary Outcome Measures
Comparison of Deceptive Box Task score
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Comparison of Look-prediction/say-prediction test score
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Comparison of Empathy Quotient score
(60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.
Comparison of Ekman 60 test score
(60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.
Comparison of Frontal Behavioral Inventory score
(24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.
Comparison of Deceptive Box Task score
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Comparison of Look-prediction/say-prediction test
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Comparison of Empathy Quotient score
(60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.
Comparison of Ekman 60 test score
(60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.
Comparison of Frontal Behavioral Inventory score
(24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.
Secondary Outcome Measures
Changes from baseline in Deceptive Box Task Test.
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Changes from baseline in Look/say Test
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Changes from baseline in Empathy Quotient scale
(60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.
Changes from baseline in Ekman 60 Test
(60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.
Changes from baseline in Frontal Behavioral Inventory
(24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.
Comparison Montreal Cognitive Assessment
(30 items). Minimum value=0, maximum value=30. Higher score means a better outcome.
Comparison of Geriatric Depression Scale score
(30 items). Minimum value=0, maximum value=30. Higher score means a better outcome.
Comparison of Euroquol-5 dimensions score
(visual analogue scale with 100-point scale). Minimum value=0, maximum value=100. Higher score means a better outcome.
Full Information
NCT ID
NCT04490616
First Posted
July 10, 2020
Last Updated
September 21, 2022
Sponsor
Ospedale Regionale di Lugano
1. Study Identification
Unique Protocol Identification Number
NCT04490616
Brief Title
TMS Treatment of Social Cognition Skills in Mild Cognitive Impairment
Official Title
EFFECTS OF rTMS TREATMENT ON SOCIAL COGNITION DYSFUNCTIONS IN MILD COGNITIVE IMPAIRMENT: AN PROSPECTIVE, DOUBLE-BINDING, RANDOMIZED, SINGLE CENTRE, EXPLORATIVE STUDY
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 11, 2021 (Actual)
Primary Completion Date
May 31, 2024 (Anticipated)
Study Completion Date
August 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ospedale Regionale di Lugano
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
Social cognitive abilities are impaired in around 17% of subjects with mild cognitive impairment (MCI), and might not reflect upon functional status. Compared to healthy controls, MCI showed impairments in theory of mind (ToM) and facial emotion recognition. Moreover, in amnesic MCI patients, reduced ToM ability appears to be correlated with worse performances at several cognitive performances. These findings, in agreement with previous evidence, confirm that impaired social cognition might occur prior to dementia: typically elderly start to show impairment in the complex ToM levels, which is found also in MCI patients and proceeds further in AD patients. Thus, the treatment of these aspects has the potential to influence the trajectory of neurodegeneration. In the last decade, it has been increasingly evident the effectiveness of active stimulation of brain regions with repetitive transcranial magnetic stimulation (rTMS), to improve cognitive and functional performances in patients with dementia.
On the other hand, brain imaging techniques and TMS stimulations have identified two main areas responsible for human social cognition- the medial prefrontal cortex (MPFC) and the right temporo-parietal junction (RTPJ).
In this project, we hypothesized that an improvement of social cognition skills may be obtained in MCI patients by using the rTMS on two main areas responsible for human social cognition- the medial prefrontal cortex (MPFC) and the right temporoparietal junction (RTPJ). Moreover, it expects that rTMS treatment may also contribute to improving cognitive abilities and neuropsychiatric aspects partially modulated by the same networks stimulated.
Detailed Description
This is a prospective, double-binding, cross-sectional, randomized, sham-controlled, and single-center project aimed to investigate the effect of rTMS treatment of social cognition abilities in MCI subjects at 2 and 4 weeks, and after 8 weeks from baseline.
All patients will be recruited at Clinical Neuroscience Institute, Department of Neurology, Regional Civic Hospital, Lugan; Department of Geriatric Italian Hospital Viganello; and Department of Geriatric, Beata Vergine Hospital Mendrisio; Southern Switzerland, Switzerland.
Primary objective:
1. To investigate whether the application of high-frequency rTMS, for 2 or 4 weeks, to the RPTJ and MPFC resulted in social cognitive improvements.
Secondary objectives:
To verify whether the social cognition benefits previously recorded might persist after 8 weeks the end of the stimulation, with a major benefit with a longer rTMS application (4 weeks).
To investigate whether the application of high-frequency rTMS, at 2 weeks or 4 weeks, to the RPTJ and MPFC contributes to improve cognitive functions as well as neuropsychiatric (depression) and functional aspects.
To verify whether the cognitive functions, neuropsychiatric aspect, and functional benefits previously recorded persist after the end of the rTMS stimulation.
Primary analysis: To investigate the behavioral effects induced by the rTMS protocol after 2 and 4 weeks of daily stimulation on social cognition skills, executive/attentive functions, neuropsychiatric and functional aspects will be used a mixed-model ANOVA, considering the group as a between-subjects factor, and time as a within-subject factor.
Secondary Analyses: To investigate the direct or mediated rTMS effect on social cognition skills, a multivariate linear regression analysis will be done for each social cognition measure (ToM, empathy, social perception, social behavior) changes after rTMS treatment at 2 and 4 weeks as the dependent factor, separately, and appropriate screening/baseline dependent variables and rTMS groups as independent factors.
The evaluation and treatment of social cognition alterations in subjects with MCI can be useful for two main aspects: first, the mild cognitive and behavior impairment of these subjects favor a better answer at the treatment, both at the behavioral level and in terms of brain structural and functional response; second, treatment of these abilities in MCI population might retard the conversion to dementia. More importantly, the detection of predominant social cognition alteration in early phases of cognitive decline might be potentially helpful to differentiate individuals who will develop frontotemporal dementia. Therefore, it is important to investigate and define a treatment protocol to limit social cognition disturbances in MCI.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Cognitive Impairment
Keywords
ripetitive transcranial magnetic stimulation treatment, social cognition, theory of mind, empathy, social perception, social behavior
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
In the project will be applied a two-site repetitive transcranial magnetic stimulation (rTMS) stimulation.
MCI patients that obtained a score ≤ 10 percentiles, at least one performance/domain of social cognition assessment will be considered impaired at social cognition abilities. In the same day of cognitive-behavioral assessment, patients will be randomly assigned to one of the two groups:
1) RR-Gr received 4 weeks of rTMS stimulation of the RTPJ and MPFC; (2) SR-Gr received of the RTPJ and MPFC sham stimulation during the first 2 weeks followed by 2 weeks of real stimulation. Each week of rTMS treatment consisted of five sessions. This paradigm has proven to be effective for improve cognitive performances in AD patients. In the sham condition, a sham coil will be used.
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
RR-GR
Arm Type
Experimental
Arm Description
MCI patients with social cognition deficits will receive 4 weeks of rTMS stimulation
Arm Title
SR-GR
Arm Type
Other
Arm Description
MCI patients with social cognition deficits will receive 2 weeks of placebo treatment, followed by 2 weeks of real rTMS stimulation
Intervention Type
Other
Intervention Name(s)
rTMS treatment
Intervention Description
A two-site rTMS stimulation delivered by a Magstim unit featuring a double 70 mm cooled coil will be applied.
MCI patients will be randomly assigned to one of the two study groups:
RR-Gr will receive 4 weeks of rTMS stimulation of the right temporo-parietal junction (RTPJ) and medial prefrontal cortex (MPFC);
PL-Gr will receive sham stimulation of the RTPJ and MPFC during the first 2 weeks followed by 2 weeks of real stimulation. Each week of rTMS treatment will consist of five sessions (50 min, one per day).
For each area target, a total of 2000 pulses at 20Hz, 3-s train duration, and 28-s inter-train interval at 100% motor threshold (MT) will be delivered per session. A fixed intensity of MT will ensure a more consistent spatial spread of TMS effects in subjects' brains not influenced by differences in individual MT. In the sham condition, a sham coil will be used.
Each session lasted for about 60 min including time for set up and 50 min of stimulation.
Primary Outcome Measure Information:
Title
Comparison of Deceptive Box Task score
Description
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Time Frame
Week 2
Title
Comparison of Look-prediction/say-prediction test score
Description
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Time Frame
Week 2
Title
Comparison of Empathy Quotient score
Description
(60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.
Time Frame
Week 2
Title
Comparison of Ekman 60 test score
Description
(60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.
Time Frame
Week 2
Title
Comparison of Frontal Behavioral Inventory score
Description
(24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.
Time Frame
Week 2
Title
Comparison of Deceptive Box Task score
Description
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Time Frame
Week 4
Title
Comparison of Look-prediction/say-prediction test
Description
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Time Frame
Week 4
Title
Comparison of Empathy Quotient score
Description
(60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.
Time Frame
Week 4
Title
Comparison of Ekman 60 test score
Description
(60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.
Time Frame
Week 4
Title
Comparison of Frontal Behavioral Inventory score
Description
(24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.
Time Frame
Week 4
Secondary Outcome Measure Information:
Title
Changes from baseline in Deceptive Box Task Test.
Description
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Time Frame
Week 12
Title
Changes from baseline in Look/say Test
Description
(5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.
Time Frame
Week 12
Title
Changes from baseline in Empathy Quotient scale
Description
(60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.
Time Frame
Week 12
Title
Changes from baseline in Ekman 60 Test
Description
(60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.
Time Frame
Week 12
Title
Changes from baseline in Frontal Behavioral Inventory
Description
(24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.
Time Frame
Week 12
Title
Comparison Montreal Cognitive Assessment
Description
(30 items). Minimum value=0, maximum value=30. Higher score means a better outcome.
Time Frame
through study completion, an average of 12 weeks
Title
Comparison of Geriatric Depression Scale score
Description
(30 items). Minimum value=0, maximum value=30. Higher score means a better outcome.
Time Frame
through study completion, an average of 12 weeks
Title
Comparison of Euroquol-5 dimensions score
Description
(visual analogue scale with 100-point scale). Minimum value=0, maximum value=100. Higher score means a better outcome.
Time Frame
athrough study completion, an average of 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects aged 50 to 85 years old, inclusive, at the time of informed consent;
Must have at least 5 years of education or work experience to exclude mental deficits other than MCI;
Must meet Petersen's criteria for mild cognitive impairment, and must have:
Clinical dementia rating global score of 0.5;
Mini-Mental State Examination score between 24 and 30;
Must have a score ≥ 26.5 at Token test to ensure that subjects have the ability to understand the instructions and procedures;
Must have a score < 29 at Beck Depression Inventory to exclude major depression that could compromise the patient's ability to engage in the study;
Apart from a clinical diagnosis of MCI, the subject must be in good health;
Must be on stable dose of antidepressant (if applicable) for at least 2 months prior to the enrolment.
Exclusion Criteria:
Any uncontrolled medical or neurological/neurodegenerative condition (other than MCI);
Clinical significant unstable psychiatric illness requiring treatment with neuroleptic;
Transient ischemic attack, stroke, or any unexplained loss of consciousness or severe ongoing stressor within 1 year prior to screening;
History of seizure within10 years prior to screening;
Recent history of alcohol or substance abuse or use of cannabinoids;
Any other medical conditions that are not stable or controlled, or could affect the subject's safety or interfere with the study assessments and treatment;
Contraindication to having TMS treatment;
Inability to understand the purpose of the study or to comply with study requirements.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Leonardo Sacco, Dr
Phone
+41 091 811 6921
Email
leonardo.sacco@eoc.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Gianna C. Riccitelli, Dr
Phone
+41 091 811 6921
Email
gianna.riccitelli@eoc.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leonardo Sacco, Dr
Organizational Affiliation
+41 091 811 6921
Official's Role
Principal Investigator
Facility Information:
Facility Name
Neurocentro della Svizzera italiana,Ospedale Regionale di Lugano
City
Lugano
State/Province
Ticino
ZIP/Postal Code
6903
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gianna C Riccitelli, PhD
Phone
091 811 6398
Email
gianna.riccitelli@eoc.ch
First Name & Middle Initial & Last Name & Degree
Leonardo Sacco, MD
Phone
091 811 6921
Email
leonardo.sacco@eoc.ch
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
22407224
Citation
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Results Reference
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PubMed Identifier
18771388
Citation
Adolphs R. The social brain: neural basis of social knowledge. Annu Rev Psychol. 2009;60:693-716. doi: 10.1146/annurev.psych.60.110707.163514.
Results Reference
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25961468
Citation
Wondra JD, Ellsworth PC. An appraisal theory of empathy and other vicarious emotional experiences. Psychol Rev. 2015 Jul;122(3):411-28. doi: 10.1037/a0039252. Epub 2015 May 11.
Results Reference
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PubMed Identifier
15701227
Citation
Apperly IA, Samson D, Chiavarino C, Humphreys GW. Frontal and temporo-parietal lobe contributions to theory of mind: neuropsychological evidence from a false-belief task with reduced language and executive demands. J Cogn Neurosci. 2004 Dec;16(10):1773-84. doi: 10.1162/0898929042947928.
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Citation
Van Overwalle F. Social cognition and the brain: a meta-analysis. Hum Brain Mapp. 2009 Mar;30(3):829-58. doi: 10.1002/hbm.20547.
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TMS Treatment of Social Cognition Skills in Mild Cognitive Impairment
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