Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

TMS Treatment of Social Cognition Skills in Mild Cognitive Impairment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04490616
Recruitment Status : Not yet recruiting
First Posted : July 29, 2020
Last Update Posted : July 31, 2020
Sponsor:
Information provided by (Responsible Party):
Leonardo Sacco, Ospedale Regionale di Lugano

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.


Condition or disease Intervention/treatment Phase
Mild Cognitive Impairment Other: rTMS treatment Not Applicable

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:

  1. 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).
  2. 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.
  3. 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention 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: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: EFFECTS OF rTMS TREATMENT ON SOCIAL COGNITION DYSFUNCTIONS IN MILD COGNITIVE IMPAIRMENT: AN PROSPECTIVE, DOUBLE-BINDING, RANDOMIZED, SINGLE CENTRE, EXPLORATIVE STUDY
Estimated Study Start Date : September 15, 2020
Estimated Primary Completion Date : May 31, 2024
Estimated Study Completion Date : August 31, 2024

Arm Intervention/treatment
Experimental: RR-GR
MCI patients with social cognition deficits will receive 4 weeks of rTMS stimulation
Other: rTMS treatment

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:

  1. RR-Gr will receive 4 weeks of rTMS stimulation of the right temporo-parietal junction (RTPJ) and medial prefrontal cortex (MPFC);
  2. 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.


SR-GR
MCI patients with social cognition deficits will receive 2 weeks of placebo treatment, followed by 2 weeks of real rTMS stimulation
Other: rTMS treatment

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:

  1. RR-Gr will receive 4 weeks of rTMS stimulation of the right temporo-parietal junction (RTPJ) and medial prefrontal cortex (MPFC);
  2. 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 Measures :
  1. Comparison of Deceptive Box Task score [ Time Frame: Week 2 ]
    (5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.

  2. Comparison of Look-prediction/say-prediction test score [ Time Frame: Week 2 ]
    (5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.

  3. Comparison of Empathy Quotient score [ Time Frame: Week 2 ]
    (60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.

  4. Comparison of Ekman 60 test score [ Time Frame: Week 2 ]
    (60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.

  5. Comparison of Frontal Behavioral Inventory score [ Time Frame: Week 2 ]
    (24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.

  6. Comparison of Deceptive Box Task score [ Time Frame: Week 4 ]
    (5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.

  7. Comparison of Look-prediction/say-prediction test [ Time Frame: Week 4 ]
    (5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.

  8. Comparison of Empathy Quotient score [ Time Frame: Week 4 ]
    (60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.

  9. Comparison of Ekman 60 test score [ Time Frame: Week 4 ]
    (60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.

  10. Comparison of Frontal Behavioral Inventory score [ Time Frame: Week 4 ]
    (24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.


Secondary Outcome Measures :
  1. Changes from baseline in Deceptive Box Task Test. [ Time Frame: Week 12 ]
    (5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.

  2. Changes from baseline in Look/say Test [ Time Frame: Week 12 ]
    (5 items). Minimum value=0, maximum value=5. A higher score means a better outcome.

  3. Changes from baseline in Empathy Quotient scale [ Time Frame: Week 12 ]
    (60 items). Minimum value=0, maximum value=80. A higher score means a better outcome.

  4. Changes from baseline in Ekman 60 Test [ Time Frame: Week 12 ]
    (60 b/w pictures). Minimum value=0, maximum value=60. Higher score means a better outcome.

  5. Changes from baseline in Frontal Behavioral Inventory [ Time Frame: Week 12 ]
    (24 items). Minimum value=0, maximum value=69. Higher score means a worse outcome.

  6. Comparison Montreal Cognitive Assessment [ Time Frame: through study completion, an average of 12 weeks ]
    (30 items). Minimum value=0, maximum value=30. Higher score means a better outcome.

  7. Comparison of Geriatric Depression Scale score [ Time Frame: through study completion, an average of 12 weeks ]
    (30 items). Minimum value=0, maximum value=30. Higher score means a better outcome.

  8. Comparison of Euroquol-5 dimensions score [ Time Frame: athrough study completion, an average of 12 weeks ]
    (visual analogue scale with 100-point scale). Minimum value=0, maximum value=100. Higher score means a better outcome.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04490616


Contacts
Layout table for location contacts
Contact: Leonardo Sacco, Dr +41 091 811 6921 leonardo.sacco@eoc.ch
Contact: Gianna C. Riccitelli, Dr +41 091 811 6921 gianna.riccitelli@eoc.ch

Sponsors and Collaborators
Ospedale Regionale di Lugano
Investigators
Layout table for investigator information
Principal Investigator: Leonardo Sacco, Dr +41 091 811 6921
Publications of Results:

Other Publications:
Layout table for additonal information
Responsible Party: Leonardo Sacco, Principal Investigator, Ospedale Regionale di Lugano
ClinicalTrials.gov Identifier: NCT04490616    
Other Study ID Numbers: 2020-00434/CE 3594
First Posted: July 29, 2020    Key Record Dates
Last Update Posted: July 31, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Leonardo Sacco, Ospedale Regionale di Lugano:
ripetitive transcranial magnetic stimulation treatment
social cognition
theory of mind
empathy
social perception
social behavior
Additional relevant MeSH terms:
Layout table for MeSH terms
Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders