Alzheimer DiseaseAD-EMTrNCT03270137
Repetitive Transcranial Magnetic Stimulation in Patients With Alzheimer Disease
A study testing repetitive transcranial magnetic stimulation- IDLPFC and repetitive transcranial magnetic stimulation - Six regions in people with Alzheimer Disease and Transcranial Magnetic Stimulation, run by Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente.
Trial summary
Randomized clinical trial, comparative and single blind aims to determine effects on cognition, psychological and behavioral symptoms and functionality of 5 Hz repetitive transcranial magnetic stimulation (rTMS) administered over left dorsolateral prefrontal cortex (lDLPFC) compared to six regions protocol, divided in… Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Alzheimer Disease, Transcranial Magnetic Stimulation
- What is being tested?
- repetitive transcranial magnetic stimulation- IDLPFC and repetitive transcranial magnetic stimulation - Six regions
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- No sites listed yet
- Study dates
- 10 Mar 2016to 31 Aug 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with file number at National Institute of Psychiatry "Ramón de la Fuente Muñiz".
- Scholarship of at least 5 years or above.
- Dementia diagnosis established by clinical examination made by their responsible physician, according the Diagnose Criteria for Alzheimer Disease for possible, mild or moderate according to DSM-5. Severity will be stratified with Mini-Mental State (MMSE-FOLSTEIN): as a) mild: 21-26 and b) moderated 15-20 points; in addition, with Reisberg Global Deterioration, the states from 2 to 4 that correspond a cognitive deficit mild and moderated.
- In the case of concomitant treatment with memantine or acetylcholinesterase inhibitors, the patient should have taken it for at least 6 months prior to study.
- In the case of other pharmacological treatments for psychiatric conditions, for example, antidepressants, anxiolytic or antipsychotics, the patient should have taken stable doses for at least 2 months.
- Patients with another no-psychiatric comorbidity should be stable (according to diagnostic criteria and supported by laboratory studies or metric assessments).
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- Every patient should have a caregiver (for example, spouse, a relative or a professional caregiver) along the study who could stay with the patient at least 10 hours/week.
- Signing of informed consent by patient and caregiver.
- Patients and caregivers who can attend in weekdays, along three weeks assessments and treatment sessions at National Institute of Psychiatry "Ramón de la Fuente Muñiz".
Who cannot join
- Patients with severe agitation symptoms or difficulties to cooperate with the study.
- Patients with history of epilepsy.
- Patients with sudden onset of apoplexy, focal neurologic findings as hemiparesis, sensory loss, visual field deficit and lack of coordination in the legs in early stages of disease.
- Convulsion or walking disorder at onset or very early stages of the disease.
- Patients with history of severe psychiatric disorders.
- Patients with alterations in a conventional electroencephalogram (paroxysmal phenomena identified by a specialized clinical neurophysiologist).
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- Patients with pacemaker or implanted metallic intracranial objects.
- Elimination criteria:
- Decision of patient or caregiver to left the study.
- Modification in doses or pharmacological treatment prior to start the study.
- Patients with new clinical findings and who require complementary pharmacological treatment.
- Presence of adverse events that could affect health and could limit maintain the patient in treatment.
- Exacerbation of cognitive or behavioral symptoms during the study.
About this study
Official title: Cognitive, Behavioral and Functional Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) in Patients With Potential Alzheimer Disease: Two Treatment Modalities Comparison
Randomized clinical trial, comparative and single blind aims to determine effects on cognition, psychological and behavioral symptoms and functionality of 5 Hz repetitive transcranial magnetic stimulation (rTMS) administered over left dorsolateral prefrontal cortex (lDLPFC) compared to six regions protocol, divided in two sub-conditions: day 1 (Broca area, Wernicke area and lDLPFC) alternated by day 2 (left and right parietal association cortex, and right dorsolateral prefrontal cortex [rDLPFC]). Main outcomes will be evaluated at ending of 15 rTMS sessions and 4 weeks after.
Read the detailed description
Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline that affects behavior and daily functionality. Its etiology is unknown and treatment efficacy is partial. Repetitive transcranial magnetic stimulation has been suggested as a potential treatment as of several trials has revealed improvements in language, episodic memory, psychological and behavioral symptoms in dementia as well as functionality using different experimental designs, stimulation parameters and cortical targets comparisons. However, it remains to determine the most effective modality, comparing outcomes with cortical targets poorly studied and how much the effects last. The main objective of this study is to determine which of two stimulation modalities provides a better cognitive and behavioral effect also on functionality in patients with potential diagnosis of AD, administered over lDLPFC (Condition A) and a six areas condition (Condition B) in which are alternated two sub-conditions (Day 1: Broca and Wernicke areas and lDLPFC, and Day 2: bilateral parietal association cortex and rDLPFC) along 15 sessions and 1500 pulses per session.
For this purpose, will be randomized 22 patients with potential diagnosis of AD (according to DSM-5) to both stimulation conditions (11 patients to each condition). The rTMS will be administered at 5 Hz and 1500 pulses per session (30 trains and 10 seconds inter-train interval) along 15 sessions with a post-treatment evaluation at 4 weeks comparing: time response, post-treatment effects and 4 weeks effects.
To evaluate clinical response among stimulation conditions will be used Alzheimer´s Disease Assessment Scale COGNITIVE (ADAS-cog), Cumming's Neuropsychiatric Inventory (NPI), Yesavage Geriatric Depression Scale (GDS), Interview for Deterioration-in-daily Living Activities in Dementia (IDDD) and Clinical Global Impression (CGI). The modified version of Mini Mental State (MMSE-FOLSTEIN) will be applied in the same time points of other evaluations also at the session 5 and 10. Other interest variables are: age, sex, civil status, education, occupation, time and type of pharmacological treatment.
- Being tested
- repetitive transcranial magnetic stimulation- IDLPFC, repetitive transcranial magnetic stimulation - Six regions
- Keywords
- Alzheimer Disease, rTMS, Cognition, Behavioral Symptoms, Functionality
- Medical subject headings
- Alzheimer Disease, Behavioral Symptoms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
repetitive transcranial magnetic stimulation- IDLPFCDevice
Repetitive transcranial magnetic stimulation (rTMS) at 5Hz administered over left dorsolateral prefrontal cortex (lDLPFC). Repetitive transcranial magnetic stimulation (rTMS) at 5Hz administered over left dorsolateral prefrontal cortex (lDLPFC) compared to six regions protocol, divided in two sub-conditions: day 1 (Broca area, Wernicke area and lDLPFC) alternated by day 2 (left and right parietal association cortex, and right dorsolateral prefrontal cortex [rDLPFC]). Main outcomes will be evaluated at ending of 15 rTMS sessions and 4 weeks after.
repetitive transcranial magnetic stimulation - Six regionsDevice
Repetitive transcranial magnetic stimulation (rTMS) at 5Hz administered on six regions protocol, divided in two sub-conditions: day 1 (Broca area, Wernicke area and lDLPFC) alternated by day 2 (left and right parietal association cortex, and right dorsolateral prefrontal cortex [rDLPFC]). Main outcomes will be evaluated at ending of 15 rTMS sessions and 4 weeks after.
| Study group | Role | What they receive |
|---|---|---|
| Condition A: rTMS on L-DLPFC | Active comparator | Repetitive transcranial magnetic stimulation- IDLPFC. The intervention will be rTMS delivered on left dorsolateral prefrontal cortex (L-DLPFC).
Every patient will receive 15 rTMS sessions (in weekdays) along three weeks at 5 Hz of frequency and at its 100% of motor threshold. Each session will consist of 30 trains separated by 10 seconds inter-train interval and 1500 total pulses per session.
Equipment to rTMS includes a Magpro R30 stimulator (Magventure, Denmark) with an 8-shape coil model MCF-B70. Receives: Device: repetitive transcranial magnetic stimulation- IDLPFC |
| Condition B: rTMS on six regions | Active comparator | Repetitive transcranial magnetic stimulation - Six regions. Two sub-conditions will alternate each session, starting with day 1: rTMS on Broca and Wernicke area and lDLPFC and then day 2: rTMS on left and right parietal association cortex (lPAC; rPAC) and right dorsolateral prefrontal cortex (rDLPFC).
Patients will receive 15 intervention sessions (in weekdays) along three weeks at 5 Hz frequency and 100% of motor threshold. Each area will receive 10 trains (500 pulses) separated by 10 seconds of inter-train interval that correspond to 1500 total pulses per session.
Equipment to rTMS includes a Magpro stimulator (Dantec, Denmark) with an 8-shape coil model MC-B70. Receives: Device: repetitive transcranial magnetic stimulation - Six regions |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes on cognitive functioning (ADAS-cog)
ADAS-cog is cognitive testing instrument to measure severity. It explores 11 domains including memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of AD.
Measured: Baseline, Post rTMS treatment: at week 3, and at week 4.
Secondary outcomes (5)
Changes on cognitive effects (Mini Mental State)
This instrument gives scores to orientation in time and space, registration information (three words) and recovering, attention, calculation, language (denomination, repetition, understanding of complex orders, reading and writing) and finally visuoconstruction (two overlapping diamonds).
Measured: Baseline, every week for 3 weeks during rTMS treatment and at the 4th week after treatment.
Changes on behavioral symptoms (NPI)
This is a diagnostic instrument to determine the presence of behavioral symptoms. It measures frequency and severity of symptoms in the last month and the overload for the caregiver. This test divides behavioral symptoms in: delirium, hallucinations, agitation or aggressivity, anxiety, euphoria, apathy, irritability/lability, disinhibition, aberrant motor behavior, sleep and appetite/feeding.
Measured: Baseline, Post rTMS treatment: at week 3, and at week 4.
Changes on depression symptoms (GDS-Yesavage)
Repeated application allows to evaluate changes in the geriatric depression evolution.
Measured: Baseline, Post rTMS treatment: at week 3, and at week 4.
Changes on effects on functionality (IDDD)
This is an instrument designed to evaluate functionality in dementia. It evaluates self-care and complex activities.
Measured: Baseline, Post rTMS treatment: at week 3, and at week 4.
Changes on Clinical Global Impression (CGI)
Standardized and descriptive scale, it gives qualitative information to identify changes in the illness through measuring severity of clinical picture and improvements triggered by treatments (change in the time) as well as treatment efficacy.
Measured: Baseline, Post rTMS treatment: at week 3, and at week 4.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2017
- Study start10 Mar 2016
- Primary completion28 Feb 2017
- Study completion31 Aug 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel Assignment
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente
- Sponsor type
- University, hospital or other
- Collaborators
- National Council of Science and Technology, Mexico
- Responsible party
- Principal investigator, Ruth Alcala Lozano, Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03270137
- Sponsor's protocol ID
- SIC-16-001
- Acronym
- AD-EMTr
- Status last verified
- Aug 2017
- First submitted
- 21 Aug 2017
- Last updated
- 1 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cognitive, Behavioral and Functional Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) in Patients With Potential Alzheimer Disease: Two Treatment Modalities Comparison
- ClinicalTrials.gov ID
- NCT03270137
- Acronym / sponsor ID
- AD-EMTr / SIC-16-001
- Keywords
- Alzheimer Disease, rTMS, Cognition, Behavioral Symptoms, Functionality
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Instituto Nacional de Psiquiatría Dr. Ramón de la FuenteUniversity, hospital or other
- Collaborators
- National Council of Science and Technology, Mexico
- Study start
- 10 Mar 2016 (actual)
- Primary completion
- 28 Feb 2017 (actual)
- Study completion
- 31 Aug 2017 (estimated)
- First posted
- 1 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Randomized clinical trial, comparative and single blind aims to determine effects on cognition, psychological and behavioral symptoms and functionality of 5 Hz repetitive transcranial magnetic stimulation (rTMS) administered over left dorsolateral prefrontal cortex (lDLPFC) compared to six regions protocol, divided in two sub-conditions: day 1 (Broca area, Wernicke area and lDLPFC) alternated by day 2 (left and right parietal association cortex, and right dorsolateral prefrontal cortex [rDLPFC]). Main outcomes will be evaluated at ending of 15 rTMS sessions and 4 weeks after.
Detailed description
Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline that affects behavior and daily functionality. Its etiology is unknown and treatment efficacy is partial. Repetitive transcranial magnetic stimulation has been suggested as a potential treatment as of several trials has revealed improvements in language, episodic memory, psychological and behavioral symptoms in dementia as well as functionality using different experimental designs, stimulation parameters and cortical targets comparisons. However, it remains to determine the most effective modality, comparing outcomes with cortical targets poorly studied and how much the effects last. The main objective of this study is to determine which of two stimulation modalities provides a better cognitive and behavioral effect also on functionality in patients with potential diagnosis of AD, administered over lDLPFC (Condition A) and a six areas condition (Condition B) in which are alternated two sub-conditions (Day 1: Broca and Wernicke areas and lDLPFC, and Day 2: bilateral parietal association cortex and rDLPFC) along 15 sessions and 1500 pulses per session.
For this purpose, will be randomized 22 patients with potential diagnosis of AD (according to DSM-5) to both stimulation conditions (11 patients to each condition). The rTMS will be administered at 5 Hz and 1500 pulses per session (30 trains and 10 seconds inter-train interval) along 15 sessions with a post-treatment evaluation at 4 weeks comparing: time response, post-treatment effects and 4 weeks effects.
To evaluate clinical response among stimulation conditions will be used Alzheimer´s Disease Assessment Scale COGNITIVE (ADAS-cog), Cumming's Neuropsychiatric Inventory (NPI), Yesavage Geriatric Depression Scale (GDS), Interview for Deterioration-in-daily Living Activities in Dementia (IDDD) and Clinical Global Impression (CGI). The modified version of Mini Mental State (MMSE-FOLSTEIN) will be applied in the same time points of other evaluations also at the session 5 and 10. Other interest variables are: age, sex, civil status, education, occupation, time and type of pharmacological treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
- Model description
- Parallel Assignment
| Arm | Type | Receives |
|---|---|---|
| Condition A: rTMS on L-DLPFC | Active comparator | Device: repetitive transcranial magnetic stimulation- IDLPFCRepetitive transcranial magnetic stimulation- IDLPFC. The intervention will be rTMS delivered on left dorsolateral prefrontal cortex (L-DLPFC). Every patient will receive 15 rTMS sessions (in weekdays) along three weeks at 5 Hz of frequency and at its 100% of motor threshold. Each session will consist of 30 trains separated by 10 seconds inter-train interval and 1500 total pulses per session. Equipment to rTMS includes a Magpro R30 stimulator (Magventure, Denmark) with an 8-shape coil model MCF-B70. |
| Condition B: rTMS on six regions | Active comparator | Device: repetitive transcranial magnetic stimulation - Six regionsRepetitive transcranial magnetic stimulation - Six regions. Two sub-conditions will alternate each session, starting with day 1: rTMS on Broca and Wernicke area and lDLPFC and then day 2: rTMS on left and right parietal association cortex (lPAC; rPAC) and right dorsolateral prefrontal cortex (rDLPFC). Patients will receive 15 intervention sessions (in weekdays) along three weeks at 5 Hz frequency and 100% of motor threshold. Each area will receive 10 trains (500 pulses) separated by 10 seconds of inter-train interval that correspond to 1500 total pulses per session. Equipment to rTMS includes a Magpro stimulator (Dantec, Denmark) with an 8-shape coil model MC-B70. |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with file number at National Institute of Psychiatry "Ramón de la Fuente Muñiz".
- Scholarship of at least 5 years or above.
- Dementia diagnosis established by clinical examination made by their responsible physician, according the Diagnose Criteria for Alzheimer Disease for possible, mild or moderate according to DSM-5. Severity will be stratified with Mini-Mental State (MMSE-FOLSTEIN): as a) mild: 21-26 and b) moderated 15-20 points; in addition, with Reisberg Global Deterioration, the states from 2 to 4 that correspond a cognitive deficit mild and moderated.
- In the case of concomitant treatment with memantine or acetylcholinesterase inhibitors, the patient should have taken it for at least 6 months prior to study.
- In the case of other pharmacological treatments for psychiatric conditions, for example, antidepressants, anxiolytic or antipsychotics, the patient should have taken stable doses for at least 2 months.
Key exclusion criteria (13 listed)
- Patients with severe agitation symptoms or difficulties to cooperate with the study.
- Patients with history of epilepsy.
- Patients with sudden onset of apoplexy, focal neurologic findings as hemiparesis, sensory loss, visual field deficit and lack of coordination in the legs in early stages of disease.
- Convulsion or walking disorder at onset or very early stages of the disease.
- Patients with history of severe psychiatric disorders.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| repetitive transcranial magnetic stimulation- IDLPFCRepetitive transcranial magnetic stimulation (rTMS) at 5Hz administered over left dorsolateral prefrontal cortex (lDLPFC). Repetitive transcranial magnetic stimulation (rTMS) at 5Hz administered over left dorsolateral prefrontal cortex (lDLPFC) compared to six regions protocol, divided in two sub-conditions: day 1 (Broca area, Wernicke area and lDLPFC) alternated by day 2 (left and right parietal association cortex, and right dorsolateral prefrontal cortex [rDLPFC]). Main outcomes will be evaluated at ending of 15 rTMS sessions and 4 weeks after. | Device | Condition A: rTMS on L-DLPFC |
| repetitive transcranial magnetic stimulation - Six regionsRepetitive transcranial magnetic stimulation (rTMS) at 5Hz administered on six regions protocol, divided in two sub-conditions: day 1 (Broca area, Wernicke area and lDLPFC) alternated by day 2 (left and right parietal association cortex, and right dorsolateral prefrontal cortex [rDLPFC]). Main outcomes will be evaluated at ending of 15 rTMS sessions and 4 weeks after. | Device | Condition B: rTMS on six regions |
Primary outcome
Changes on cognitive functioning (ADAS-cog)
Time frame: Baseline, Post rTMS treatment: at week 3, and at week 4.
ADAS-cog is cognitive testing instrument to measure severity. It explores 11 domains including memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of AD.
5 secondary outcomes
Changes on cognitive effects (Mini Mental State)
Time frame: Baseline, every week for 3 weeks during rTMS treatment and at the 4th week after treatment.
Changes on behavioral symptoms (NPI)
Time frame: Baseline, Post rTMS treatment: at week 3, and at week 4.
Changes on depression symptoms (GDS-Yesavage)
Time frame: Baseline, Post rTMS treatment: at week 3, and at week 4.
Changes on effects on functionality (IDDD)
Time frame: Baseline, Post rTMS treatment: at week 3, and at week 4.
Changes on Clinical Global Impression (CGI)
Time frame: Baseline, Post rTMS treatment: at week 3, and at week 4.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2017.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing repetitive transcranial magnetic stimulation- IDLPFC and repetitive transcranial magnetic stimulation - Six regions in people with Alzheimer Disease and Transcranial Magnetic Stimulation, run by Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes on cognitive functioning (ADAS-cog) (time frame: Baseline, Post rTMS treatment: at week 3, and at week 4.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2017.