Clinical trial NCT01490021: Influence of Repetitive Transcranial Magnetic Stimulation (rTMS) Challenge on Cognitive and Functional Magnetic Resonance Imaging Markers in Healthy Subjects
Official title: Influence of Repetitive Transcranial Magnetic Stimulation (rTMS) Challenge on Cognitive and Functional Magnetic Resonance Imaging Markers in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Healthy
Keywords: Healthy young men
Lead sponsor: Qualissima
Sponsor class: OTHER
Collaborators: name: Pharmacog's project (IMI)
First posted: 2011-12-12
Enrollment: 14
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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 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.

Primary outcomes:
measure: Part A: Location of cerebral activities
timeFrame: Day 1
measure: Part B: Outputs of the memory task
timeFrame: Change between Day 2 and Day 1
Secondary outcomes:
measure: Part A: The outputs of the memory task
timeFrame: Day 1 and Day 2
measure: Part B: Imaging and CANTAB tasks
timeFrame: Day 1, 2, 3 and 4
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: IDIBAPS
Study officials:
affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer
name: David Bartrés-Faz
role: PRINCIPAL_INVESTIGATOR
References: