Influence of Repetitive Transcranial Magnetic Stimulation (rTMS) Challenge on Cognitive and Functional Magnetic Resonance Imaging Markers in Healthy Subjects

This study has been terminated.
(Study stopped for scientific reasons. Another study with a new design is in course of authorization and implementation)
Sponsor:
Collaborator:
Pharmacog's project (IMI)
Information provided by (Responsible Party):
Qualissima
ClinicalTrials.gov Identifier:
NCT01490021
First received: November 28, 2011
Last updated: May 14, 2013
Last verified: May 2013
  Purpose

Episodic and working memory processes are the most affected cognitive domains in Alzheimer's Disease (AD) and its early stage, Mild Cognitive Impairment (MCI). Transcranial Magnetic Stimulation (TMS) is a unique tool to interfere with cognitive processes by inducing "virtual and transient lesions", mimicking those observed in MCI. It has proven repeatedly its capacity to interfere with encoding-retrieval memory task. However, to date, only few imaging data exist on the cerebral pathways involved in encoding memory task. Moreover, the stability of TMS effects over time remains to be investigated. If proven to be a stable interfering challenge, TMS could be used to investigate the potential restoring effect of new medication in AD.

The study is the pilot study of a larger clinical trial which aims to prove the utility of rTMS as a potential model for prediction of clinical efficacy using a combination of cognitive and neuroimaging endpoints.


Condition Intervention
Healthy
Procedure: rTMS/Active TBS
Procedure: rTMS/Placebo TBS

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Influence of Repetitive Transcranial Magnetic Stimulation (rTMS) Challenge on Cognitive and Functional Magnetic Resonance Imaging Markers in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Qualissima:

Primary Outcome Measures:
  • Part A: Location of cerebral activities [ Time Frame: Day 1 ] [ Designated as safety issue: No ]

    Primary endpoints:

    The location of cerebral activities elicited by the retrieval session of the episodic memory task during fMRI will be the primary endpoint of PART A.

    PART A will assess task-elicited BOLD signal modifications and determine the target location coordinates and verify the stability of the BOLD signal responses over time and the stability of the target location


  • Part B: Outputs of the memory task [ Time Frame: Change between Day 2 and Day 1 ] [ Designated as safety issue: No ]
    Outputs: the number of correct answers during the retrieval blocks (Hit rates)and the number of false recognition of novel pictures (False Alarms rate).


Secondary Outcome Measures:
  • Part A: The outputs of the memory task [ Time Frame: Day 1 and Day 2 ] [ Designated as safety issue: No ]
    Memory task. The output of the task will be the number of correct answers during the retrieval blocks (i.e. correctly recognized images presented during the encoding blocks, Hits rate) and the number of false recognition of novel pictures (False Alarms rate).

  • Part B: Imaging and CANTAB tasks [ Time Frame: Day 1, 2, 3 and 4 ] [ Designated as safety issue: No ]

    Imaging (functional MRI): Modifications will be highlighted by changes in the Blood-Oxygen-Level Dependence (BOLD) signal patterns.

    CANTAB tasks:

    • CANTAB / Rapid Visual Information Processing (RVP) with outcome measures: latency, probabilities and sensitivity and hits, misses, false alarms and rejections;
    • CANTAB / Spatial Working Memory (SWM) with outcome measures: errors, strategy and latency measures.
    • CANTAB / Paired Associates Learning (PAL) with outcome measures: errors, number of trials required to locate the pattern(s) correctly, memory scores.


Enrollment: 14
Study Start Date: December 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rTMS/Active TBS
A continuous Theta-Burst Stimulation (TBS) protocol will be applied over the left dorsolateral prefrontal cortex. Three stimuli at 50Hz, 80% of individual Motor Threshold will be repeated every 200ms for 40sec (Galea et al., 2010; Oberman and Pascual-Leone, 2009).
Procedure: rTMS/Active TBS
A continuous Theta-Burst Stimulation (TBS) protocol will be applied over the left dorsolateral prefrontal cortex. Three stimuli at 50Hz, 80% of individual Motor Threshold will be repeated every 200ms for 40sec (Galea et al., 2010; Oberman and Pascual-Leone, 2009).
Placebo Comparator: rTMS/Placebo TBS
rTMS/Placebo TBS
Procedure: rTMS/Placebo TBS
rTMS/Placebo TBS

Detailed Description:

Episodic and working memory processes are the most affected cognitive domains in Alzheimer's Disease (AD) and its early stage, Mild Cognitive Impairment (MCI). Transcranial Magnetic Stimulation (TMS) is a unique tool to interfere with cognitive processes by inducing "virtual and transient lesions", mimicking those observed in MCI. It has proven repeatedly its capacity to interfere with encoding-retrieval memory task. However, to date, only few imaging data exist on the cerebral pathways involved in encoding memory task. Moreover, the stability of TMS effects over time remains to be investigated. If proven to be a stable interfering challenge, TMS could be used to investigate the potential restoring effect of new medication in AD.

The study is the pilot study of a larger clinical trial which aims to prove the utility of rTMS as a potential model for prediction of clinical efficacy using a combination of cognitive and neuroimaging endpoints.

This pilot study specifically aims:

  • to determine the cerebral region to stimulate using functional neuronavigation,
  • to evaluate the effects of rTMS on behavioral and functional imaging data (functional Magnetic Resonance Imaging, fMRI)
  • to investigate the stability of the TMS interfering effects by replicating the experimental day up to 4 times.

The study is composed of two parts:

  • Part A: on Day 1, the subjects will perform the episodic memory task in the MRI scanner to determine individual main activations. The mean activation peak obtained by a group analysis will be used as the target coordinates during the part B. Two weeks later, on Day 2, the subjects will repeat the episodic memory task in the MRI scanner. The BOLD signal changes will be compared between Day 1 and Day 2 to investigate the stability of the activations elicited by the memory task.
  • Part B: subjects will randomly be assigned to Group 1 or 2.

    • GROUP 1: The subjects will come on 4 different days. On each day, the subjects will perform the episodic memory task while being actively stimulated using rTMS over L-DLPFC and Vertex (control region) in random order and will undergo an fMRI session on Day 1 and Day 2. Later, they will undergo another set of behavioral tasks from the CANTAB battery and will be stimulated by rTMS using a placebo coil.
    • GROUP 2: The subjects will come on 4 different days. On each day, the subjects will perform the episodic memory task while being actively stimulated using rTMS over L-DLPFC and Vertex (control region) in random order and will undergo an fMRI session on Day 1 and Day 2. Later, they will undergo another set of behavioral tasks from the CANTAB battery and will be stimulated by rTMS using an active coil.

Total expected number of subjects:

34 subjects for the Parts A and B PART A: 10 subjects PART B: 24 subjects (12 per group)

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Demography

  1. Healthy male subjects aged between 18 and 40 years-old inclusive.
  2. BMI between 18 kg/m2 to 29 kg/m2.
  3. Education level: at least secondary.
  4. Right-handed (Edinburgh Handedness Inventory).

    • Health status
  5. The subjects is in good health on the basis of the medical interview (medical history, symptoms) and the physical examination, vital signs.
  6. No history of psychiatric or neurological disorders as assessed by Structured Clinical Interview for DSM IV Disorders (SCID).
  7. No history of concussion with loss of consciousness more than 20 min.
  8. No history of drug or alcohol abuse.

    • Specific to the study
  9. The subject can complete the neuropsychological test battery during the training session.

    • Regulations
  10. The subject is able to read and understand the Information Form and comply with the protocol instructions and restrictions
  11. The subject is covered by a social insurance
  12. The subject have provided written informed consent

Exclusion Criteria:

  • Medical history and clinical status

    1. History or presence of psychiatric illness (Psychiatric interview).
    2. History or presence of neurologic illness.
  • General conditions 3. The subject, in the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any other reason.

    4. The subject participates in another clinical trial or is still being within a washout period of 1 month since last taking of a previous clinical trial, or subjects who have received more than 4500 Euros in the previous 12 months for participating in clinical trials.

  • Specific to the study 5. Presence of metallic objects within the head. 6. Subjects with pacemaker. 7. Claustrophobia. 8. Individual and familial history of seizure. 9. Any medication listed in the safety guidelines published by the Safety of TMS Consensus Group (Rossi et al., 2009) will be forbidden.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01490021

Locations
Spain
IDIBAPS
Barcelona, Spain
Sponsors and Collaborators
Qualissima
Pharmacog's project (IMI)
Investigators
Principal Investigator: David Bartrés-Faz IDIBAPS
  More Information

No publications provided

Responsible Party: Qualissima
ClinicalTrials.gov Identifier: NCT01490021     History of Changes
Other Study ID Numbers: WP1P002
Study First Received: November 28, 2011
Last Updated: May 14, 2013
Health Authority: Spain: Comité Ético de Investigación Clínica

Keywords provided by Qualissima:
Healthy young men

ClinicalTrials.gov processed this record on September 18, 2014