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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01490021
• Other study ID #: WP1P002
• Status: Terminated
• Phase: N/A
• First received: November 28, 2011
• Last updated: May 14, 2013
• Start date: December 2011
• Est. completion date: December 2012

Study information

• Verified date: May 2013
• Source: Qualissima
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Comité Ético de Investigación Clínica
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy

Intervention

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).
• rTMS/Placebo TBS
rTMS/Placebo TBS

Locations

Country	Name	City	State
Spain	IDIBAPS	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Qualissima	Pharmacog's project (IMI)

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Location of cerebral activities	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	Day 1	No
Primary	Part B: Outputs of the memory task	Outputs: the number of correct answers during the retrieval blocks (Hit rates)and the number of false recognition of novel pictures (False Alarms rate).	Change between Day 2 and Day 1	No
Secondary	Part A: The outputs of the memory task	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).	Day 1 and Day 2	No
Secondary	Part B: Imaging and CANTAB tasks	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.	Day 1, 2, 3 and 4	No