Efficacy and safety of infra-low-frequency transcranial magnetic stimulation in Alzheimer's disease patients with behavioral and psychological symptoms of dementia: study protocol for a randomized parallel-design controlled trial
Mo Li1, Ji-hui Lyu1, Yi Zhang2, Mao-long Gao3, Ya-nan Gao4, Meng-nan Cui1
1 Dementia Unit, Beijing Geriatric Hospital, Beijing, China
2 Department of Scientific Research and Teaching, Beijing Geriatric Hospital, Beijing, China
3 The Geriatric Institute for Clinic and Rehabilitation, Beijing Geriatric Hospital, Beijing, China
4 Department of Rehabilitation Medicine, Beijing Geriatric Hospital, Beijing, China
|Date of Web Publication||2-Aug-2017|
Dementia Unit, Beijing Geriatric Hospital, Beijing
Source of Support: This study was supported by the Beijing Municipal Administration of Hospitals' Youth Programme of China, No. QML20162101., Conflict of Interest: None
Background and objectives: Patients with Alzheimer's disease (AD) often experience abnormal mental and behavioral symptoms. Clinically, antipsychotic and antidepressant drugs are often used to control behavioral and psychological symptoms of dementia (BPSD), but these drugs have anticholinergic and vertebral effects and have the risk of affecting metabolic diseases and increasing stroke mortality. Infra-low-frequency transcranial magnetic stimulation (ILF-TMS) can regulate the electrical activity of each transmitter, modulating the physiological function of the transmitter to achieve therapeutic effects. Thus, this randomized parallel-design controlled trial examined the use of ILF-TMS as a treatment for BPSD in patients with AD. The study aims to evaluate the efficacy and safety of ILF-TMS in patients with AD who also show BPSD following conventional drug therapy.
Design: This is a randomized parallel-design controlled trial.
Methods: AD patients with BPSD in the Beijing Geriatric Hospital, China will be randomized into control (sham stimulation) and stimulation groups (n = 50/group). Eight patients from each group will participate in a preliminary experiment, and the remaining 42 will participate in the trial. For the stimulation group, along with conventional drug therapy, participants will be exposed to ILF-TMS (stimulation frequency < 0.2 Hz; total magnetic field strength, 0.1–40 mT) for 20 minutes per exposure 5 times/week for 8 consecutive weeks. Patients in the control group will undergo sham stimulation and conventional drug therapy.
Outcome measures: The primary outcome measure will be neuropsychiatric inventory score differences observed before treatment, at 4 and 8 weeks of treatment, and 4 weeks after treatment. The secondary outcome measures will be Mini-Mental State Examination and Barthel Index scores before treatment, at 4 and 8 weeks of treatment, and 4 weeks after treatment.
Discussion: The trial is intended to explore a potential new approach for the treatment of behavioral and psychiatric symptoms in patients with AD. This will help to improve poor mental symptoms and the quality of life and reduce psychological and social burdens.
Ethics and dissemination: The protocols have been approved by the ethics committee of Beijing Geriatric Hospital of China (approval No. 2016-021) on November 11th, 2016. Study design completed October 2016; ethical approval received November 2016; clinical registration conducted January 2017; patient recruitment began January 2017. Each patient will receive 8 weeks of treatment and 4 weeks of follow-up. Follow-up will be completed December 2017, and data analysis will be completed December 2018. Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals.
Trial registration: This trial has been registered in the Chinese Clinical Trial Registry (registration No. ChiCTR-INR-17010487) on January 20th, 2017.
Keywords: clinical trial; Alzheimer′s disease; infra-low-frequency transcranial magnetic stimulation; behavioral and psychological symptoms of dementia; Neuropsychiatric Inventory; Mini-Mental State Examination; Barthel Index; randomized parallel controlled trial
|How to cite this article:|
Li M, Lyu Jh, Zhang Y, Gao Ml, Gao Yn, Cui Mn. Efficacy and safety of infra-low-frequency transcranial magnetic stimulation in Alzheimer's disease patients with behavioral and psychological symptoms of dementia: study protocol for a randomized parallel-design controlled trial. Asia Pac J Clin Trials Nerv Syst Dis 2017;2:99-107
|How to cite this URL:|
Li M, Lyu Jh, Zhang Y, Gao Ml, Gao Yn, Cui Mn. Efficacy and safety of infra-low-frequency transcranial magnetic stimulation in Alzheimer's disease patients with behavioral and psychological symptoms of dementia: study protocol for a randomized parallel-design controlled trial. Asia Pac J Clin Trials Nerv Syst Dis [serial online] 2017 [cited 2018 Feb 19];2:99-107. Available from: http://www.actnjournal.com/text.asp?2017/2/3/99/211591
| Introduction|| |
Alzheimer's Disease (Ad) Is a Progressive Neurodegenerative Disease With Clinical Manifestations That Includes the Decline of Memory and Cognitive Function and a Progressive Decrease in Daily Living Ability and Is Accompanied by Neuropsychiatric and Behavioral Disorders (Burns and Iliffe, 2009). Alzheimer's Disease Has Become the Fourth Leading Cause of Death in Elderly Chinese People, Following Heart Disease, Cancer, and Cerebrovascular Diseases (Wang et al., 2012). the Prevalence of Ad in Adults Aged More Than 65 Years Is 6.6%, and the Number of Patients Increases Exponentially With Age So That 25–50% of People Aged More Than 85 Years Have Been Diagnosed With the Disease (Xie et al., 2004). at Present, Ad Has Become a Serious Public Health and Social Problem That Endangers Physical and Mental Health, Disabling Many Within the Elderly Population.
In the development of the disease, patients with AD often experience abnormal mental and behavioral symptoms, which are the behavioral and psychological symptoms of dementia (BPSD), such as irritability, agitation, depression, aggression, and delusions (Cerejeira et al., 2012). The overall incidence of BPSD is high and can reach 70–90% at specific stages of Alzheimer's disease (Finkel et al., 1996; Xie et al., 2004). Clinically, antipsychotic and antidepressant drugs are often used to control BPSD, but these drugs have anticholinergic and vertebral effects and have the risk of affecting metabolic diseases and increasing stroke mortality (Kales et al., 2015). Therefore, treatment of BPSD is controversial. Clinical research has begun examining a variety of nondrug treatments, such as behavioral intervention, supportive psychotherapy, multisensory stimulation therapy, music therapy, reminiscence therapy, and transcranial magnetic stimulation (de Oliveira et al., 2015). Transcranial magnetic stimulation (TMS) as an adjunctive therapy has some advantages, including that it is painless, noninvasive, and causes few adverse reactions (Nardone et al., 2012).
TMS, a noninvasive brain stimulation technique based on the theory of electromagnetic fields, improves the motor potential of cortical neurons by altering the induction current in the cerebral cortex, thereby affecting substance metabolism and electrophysiological activity in the brain and regulating cortical function. This technique alters cortical excitability and improves plasticity and connectivity in cortical neurons (Nardone et al., 2012). It changes cortical blood flow and metabolism at the target site, increases the ability to repair damaged cells, activates some dormant brain cells, delays cell death cycle, promotes nerve regeneration and reconstruction, and promotes the expression of brain-derived neurotrophic factor (Müller et al., 2000). Therefore, TMS plays a positive role in the rehabilitation of patients with cerebral infarction, epilepsy, and Parkinson's disease and has been increasingly more widely used in the areas of neurological disease, mental disease, and rehabilitation (Bentwich et al., 2011; Cotelli et al., 2011; Ahmed et al., 2012; Rabey et al., 2013).
In addition, TMS offers unique advantages and potentials in the treatment of AD. For example, TMS can improve cognitive function in patients with AD, and this improvement can last for at least 3 months (Bentwich et al., 2011; Cotelli et al., 2011; Ahmed et al., 2012; Rabey et al., 2013). Bentwich et al. (2011) demonstrated that after combination therapy of TMS and cognitive function training, AD assessment scale-cognition scores significantly improve, and this improvement is maintained for 4.5 months. Ahmed et al. (2012) confirmed that TMS improves cognitive function in patients with mild to moderate AD, and the effect lasts for at least 3 months. Citelli et al. (2011) found that TMS improves naming, listening, and understanding skills in AD, but it does not improve all cognitive functions. Although most studies using TMS in the treatment of AD have examined cognitive function, the effects of TMS on behavior and psychiatric symptoms in AD is less well studied. By contrast, many reports have confirmed that TMS treatment in some psychiatric disorders is effective for refractory hallucinations, depression, and anxiety (Vercammen et al., 2010; Kozel et al., 2011; Wang et al., 2013; Chen et al., 2014; Li et al., 2014; Desarkar et al., 2015; Janicak and Dokucu, 2015). Thus, we hypothesized that TMS treatment would have similar positive effects on BPSD in patients with AD.
Infra-low-frequency transcranial magnetic stimulation (ILF-TMS) is a technique based on TMS that takes advantage of the principle of biological resonance combined with encephalofluctuography. The technique produces a specific induction current in the brain by adding a certain magnetic field to the head, strengthens the ultra-slow wave power of each neurotransmitter, and regulates the electrical activity of each transmitter, modulating the physiological function of the transmitter to achieve therapeutic effects. Thus, this randomized parallel-design controlled trial examined the use of ILF-TMS as a treatment for BPSD in patients with AD.
Product indications, contraindications, and precautions
Overall, single-pulse TMS is relatively safe compared with repetitive TMS, which has slightly more adverse effects, and high-frequency TMS, which can cause seizures in some patients (Müller et al., 2000). To date, long-term adverse effects of TMS have not been reported. Some study results indicate that pregnant women should be cautious when considering TMS and that patients with epilepsy or permanent metal implants or pacemakers should be protected from high-frequency TMS. The electrical resistivity of the skin, subcutaneous tissue, and skull is much greater than that in brain neurons. During treatment with ILF-TMS, only very small electrical currents pass through the scalp and skull, and the participants are relatively comfortable and safe. The main adverse effect of low-frequency TMS is minor headache, which generally does not damage brain tissue (Zhang, 2014).
This study aims to assess the safety and efficacy of ILF-TMS adjunct therapy for BPSD in patients with AD and BPSD along with conventional drug treatment to explore a potential new treatment for BPSD.
| Methods/Design|| |
This randomized parallel-design controlled trial will be conducted in the Beijing Geriatric Hospital of China. A total of 100 AD patients with BPSD will be recruited and randomized into one of two groups: stimulation and sham stimulation (n = 50 per group). Eight patients from each group will participant in a preliminary experiment, and the remaining 42 patients will participant in the formal trial. In the stimulation group, along with conventional drug therapy, the patients will be subjected to ILF-TMS at a stimulation frequency less than 0.2 Hz and a total magnetic field strength between 0.1 and 40 mT for 20 minutes per exposure, 5 times/week for 8 consecutive weeks. The patients in the control group will undergo sham stimulation. Evaluation will be performed before treatment, at 4 and 8 weeks of treatment, and 4 weeks after treatment. The primary outcome measure will be neuropsychiatric inventory (NPI) score differences observed before treatment, at 4 and 8 weeks of treatment, and 4 weeks after treatment. The secondary outcome measures will be Mini-Mental State Examination and Barthel Index scores before treatment, at 4 and 8 weeks of treatment, and 4 weeks after treatment. The safety evaluation will include adverse events, measures of heart rate, blood pressure, conventional blood indexes, and blood biochemical indexes as well as electrocardiogram and electroencephalogram results.
Patients with AD and BPSD in the Beijing Geriatric Hospital, China.
Patients presenting with all of the following criteria will be considered for study inclusion.
- Diagnosis of AD based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria (McKhann et al., 1984)
- BPSD, that is, NPI score ≥ 10 (Cummings, 1997)
- Men and women aged 65–85 years
- Informed consent provided by the patient and family
Patients with one or more of the following conditions will be excluded from this study.
- History of seizures or severe physical illness
- Metal implants or cardiac pacemakers
- Significantly increased intracranial pressure
- History of craniocerebral surgery
- Severe alcohol abuse
- History of emotional disorder before the onset of illness
- Participation in other clinical trials
Patients who meet one or more of the following criteria during the trial will be withdrawn from this study.
- Complications that affect efficacy and safety judgments or onset of disease that may affect outcomes
- Use of other therapies or drugs to increase the speed of recovery
The study design was completed in October 2016. Ethical approval was received in November 2016. Clinical registration was conducted in January 2017. Patient recruitment began January 2017. Each patient will receive 8 weeks of treatment and 4 weeks of follow-up. The follow-up will be completed December 2017. Data analysis will be completed December 2018.
Outpatients in Memory Clinic and inpatients in Dementia Unit will be recruited by dementia specialists. Potential participants will be able to contact the project manager via telephone, email, and WeChat.
The baseline information that will be collected is shown in [Table 1].
Patients will be randomized into sham control and stimulation groups.
Group assignments will be hidden in opaque envelopes. A code will be written on each envelope. When participants meeting the inclusion criteria enter the trial, they will be assigned a number. The envelope with the corresponding number will be opened, and the participant will undergo the intervention indicated in the envelope.
The treatment protocol for each participant will be determined by a random sequence of generated data. Patients and assessors will be blinded to group information.
Both groups of patients will receive nootropics, such as memantine and donepezil, and basic treatment for physical illnesses. The type and dose of antipsychotic drugs previously prescribed will be maintained during the study.
In both groups, levels of neurotransmitters, including γ-aminobutyric acid, glutamate, acetylcholine, norepinephrine, 5-hydroxytryptamine, and dopamine, will be determined using SP03 encephalofluctuography (Shenzhen Kangli Hi Tech Co., Ltd., Shenzhen, China). Encephalofluctuogram is a method of detecting brain function initiated by China (Mei, 1995). The technique uses multiple spectrum analysis and nonlinear processing to extract the ultra slow fluctuation components in 1–255 mHz range from the electroencephalogram signals (Mei, 1984). It can reflect the activities of various neurotransmitters, such as γ-aminobutyric acid, glutamate, acetylcholine, serotonin, norepinephrine and dopamine, thereby reflecting brain function (Mei, 1984). The advantage is that it can noninvasively and quantitatively reflect the activity of neurotransmitters in the brain and the functional state of the brain.
Stimulation group: The name of the highly expressed neurotransmitters will be input into a KF-10 infra-low-frequency transcranial magnetic stimulator (Shenzhen Kangli Hi Tech Co., Ltd.). Magnetic stimulation will be conducted for these various neurotransmitters, including γ-aminobutyric acid, glutamate, acetylcholine, norepinephrine, 5-hydroxytryptamine, and dopamine. The magnetic field strength and the time required for each neurotransmitter will be adjusted. The stimulation frequency will be < 0.2 Hz and the total magnetic field strength will be 0.1–40 mT for 20 minutes of exposure 5 times/week for 8 consecutive weeks.
Control group: The magnetic stimulator will be galvanized, but no stimulation will be given.
Evaluation of efficacy and safety
Efficacy will be evaluated by two attending physicians from the Dementia Unit using a specially developed assessment manual before treatment, at 4 and 8 weeks of treatment, and 4 weeks after treatment.
Primary outcome measure
The difference in NPI scores before treatment, at 4 and 8 weeks of treatment, and 4 weeks after treatment. The NPI, developed by Cummings et al. (1997), is a scale to assess psychiatric and behavior symptoms. The NPI examines 10 subdomains of behavioral functioning: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, and aberrant motor activity. Each factor will be rated for severity (0–3 points) and symptom frequency (0–4 points). The scoring index will include factor scores (frequency × severity) and a total score (0–144 points). Higher scores represent more severe psychotic symptoms (Cummings, 1997).
Secondary outcome measures
- Mini-Mental State Examination: This scale, used extensively in clinical and research settings to measure cognitive impairment, contains a total of 30 items in the following categories: orientation to time, orientation to place, registration, attention, and calculation, recall, language, repetition, and complex commands. Thus, scores range from 0 to 30 points. Test scores are strongly associated with educational level. The normal boundary value standards are as follows: illiterate (uneducated) ≥ 17 points; primary school (schooling ≤ 6 years) ≥ 20 points; secondary school and above (schooling > 6 years) ≥ 24 points. Mini-Mental State Examination has a high reliability and validity (Pangman et al., 2000).
- Barthel Index: This scale measures performance in activities of daily living using 10 variables, including fecal incontinence, urinary incontinence, grooming, toilet use, feeding, transfers (e.g., from chair to bed), walking, dressing, climbing stairs, and bathing. Administration of the test takes between 5 and 10 minutes. The scale yields a score of 0–100 and is interpreted as follows: ≥ 95 points, completely independent; 75–94 points, mildly dependent; 50–74 points, moderately dependent; 21–49 points, severely dependent; ≤ 20 points, completely dependent (Sulter et al., 1999).
During stimulation, a physician will record adverse events, detect heart rate and blood pressure, examine conventional blood and biochemical indexes, and interpret electrocardiograms and electroencephalograms on the day of NPI evaluation.
The schedule of outcome measurement assessments is shown in [Table 2]. The trial flowchart is shown in [Figure 1].
An inspector will conduct an audit every 2 weeks. In the early stage of the trial, the inspector will obtain the clinical trial application, prepare trial protocols, clinical evaluation reports, and information consent forms, select qualified researchers, obtain institution ethics committee/institution review board approval, complete personnel training, and identify the protocols. During the trial, the inspector will focus on monitoring the test schedule, ensuring that informed consent is obtained, reviewing the case report forms, verifying the source data, assisting in creating reports regarding adverse events and serious adverse events, filing documents, and evaluating trial implementation. In the late stage of the trial, the inspector will guide the researchers in completing the necessary test documents according to regulations and explain the responsibilities to the researchers after the trial.
Sample size calculation
We used a power of 1 – β = 0.90, with a significance level of α = 0.05.
The difference in NPI scores has been commonly used as a primary outcome in both groups after treatment (Yang et al., 2014; Yang et al., 2015). Given μα = 0.05, μβ = 0.10, standard deviation (σ) =15, and tolerance error (δ) = 10, we calculated a final effective sample size for n1 = n2 of approximately 33 per group using the sample size estimation formula .
If we assume a patient loss rate of 20%, we will require n1 = n2 = 42 patients per group. Therefore, we selected a sample size of 50 patients per group so that 8 patients from each group will be available to participant in a preliminary experiment, and the remaining 42 patients will participate in the trial.
A database will be established using EpiData 3.0 software (EpiData Association, Odense, Denmark). Statistical analyses will be performed using SPSS 13.0 software (SPSS, Chicago, IL, USA). Measurement data will be expressed as the mean ± standard deviation. The data between groups will be compared using repeated measures analysis of variance. Qualitative data will be compared using the chi-square test. The significance level will be α = 0.05, and two-sided tests will be used.
Summary statistics of safety endpoints will be provided as appropriate (count, percentage, median, and standard deviation).
A summary of the mean and standard deviation of laboratory results and vital signs relative to baseline will be provided during each treatment cycle. A summary of the number and percentage of laboratory values relative to baseline deterioration will be provided.
Criteria and reasons for selection of participants included in the analysis: (1) full analysis set: All patients who are randomized to groups, receive at least one treatment, and have post-intervention evaluation data will be included in this analyses. Any missing data relevant to determining efficacy in the population will be supplemented by the last observation data. (2) Per protocol set: The treatment effect will be statistically analyzed in participants who conform to the test plan, have good compliance, have not taken disallowed drugs during the test, and fill in the case report form or for participants whose times of treatment reach 80–120% of the number of experimental requirements. (3) Safety set: All patients, who are randomized to groups and receive at least one treatment.
Case report forms will be completed by clinical researchers, who will ensure accurate, complete, and timely data entry. Electronic data will be uploaded into EpiData 3.0 software (EpiData Assocation). After checking the data, the database will be locked by the main investigator. Locked data will not be changed. The data will be statistically analyzed by statisticians. The published data will be publicly available at www.figshare.com .
Feasibility analysis of the present study
The ILF-TMS approach has several key advantages, including that it is noninvasive, safe, presents a low risk, and is generally accepted by patients. Thus, ILF-TMS has a great potential for clinical application, and our team has much experience in using this approach.
The investigator and other staff involved in the study will perform their duties, strictly follow the clinical trial protocol, and adopt standard operating procedures to ensure the implementation of the quality control and quality assurance systems.
During the clinical trial, all observations and findings will be verified, and quality control will conducted at each stage of data processing to ensure that the data are complete, accurate, authentic, and reliable.
Original documents and case report forms will be examined with a focus on compliance, integrity, consistency, and severe adverse events.
Severe adverse events will be reported to the ethics committee within 24 hours.
Documents submitted to the ethics committee during the trial will contain test plan amendments, informed consent amendments, severe adverse event reports, and participant recruitment advertisements (if adopted).
Ethical requirements and informed consent
The protocols have been approved by the Ethics Committee of Beijing Geriatric Hospital of China (approval No. 2016-021). Written informed consent will be provided by the patients and their families after they have indicated that they fully understand the treatment plan. This article adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidance for protocol reporting (Additional file 1).[Additional file 1]
Adverse events refer to adverse medical events that occur after ILF-TMS, but may not have a causal relationship with treatment. Severe adverse events are events requiring hospitalization or prolonged hospitalization leading to disability, impairing the ability to work, threatening life, or leading to congenital malformations during the trial.
In the event of severe adverse events, clinicians will report details within 2 hours to the project leader, the ethics committee, and the sponsor for the first occurrence. The original data will contain when, the manner (such as, telephone, fax, or written document), and to whom the severe adverse events were reported. Clinical physicians will report and record adverse events simultaneously. The record will include the following: a description of the adverse events, time of occurrence, time of termination, extent and frequency of seizure, and need for treatment, and if necessary, the physicians will record the treatment given. If severe adverse events occur, the drugs administered to the participants will be immediately identified and the main investigator will determine which group the participant was assigned to. Once this unblinding occurs, the patient will be dropped from the study, and the clinical examiner will be informed. The reason and date of unblinding will be recorded in the case report forms by the investigator, who will sign his or her name on the case report forms.
The adverse events will be clearly defined, and the criteria for judging the severity of adverse events, and the classification criteria for the relationship between adverse events and test drugs (such as certainly related, possibly related, possibly unrelated, unrelated, and cannot determine) will be defined in the trial design. Before the trial, team members will be familiar with the participants and an emergency preplan for the prevention and treatment of medical problems. Clinical physicians will perform any necessary treatment based on the condition of the participant. If necessary, the preplan will be carried out during prevention and treatment of medical problems.
Deviations from clinical trial protocols and revisions to clinical trial protocols
All important deviations concerning the inclusion/exclusion criteria, program implementation, patient management, and evaluation protocol will be listed.
In the summary report, deviations will be properly summarized according to center and type, for example, did not meet the inclusion criteria, but entered the test; met the withdrawal criteria, but did not withdraw; accepted the wrong treatment or dose; used prohibited drugs. Participants with deviations will be listed in the annex to the summary report; for example, multicenter studies will be classified as centers. For important deviations, the timing, cause, and effect on outcomes will be described. The severity of deviations, as well as the frequency and types of missing values, will be described in the summary report along with any other issues, and the potential impact on the results will be described. In the event of severe or persistent deviations, the agency may decide to suspend participants from the clinical trial.
Direct access to source data and files
The participants will authorize test monitors, inspectors, and the ethics committee to have access to the original medical records directly by informed consent for the verification of test procedures or test data. These authorized persons will abide by the confidentiality requirements.
Contents in the clinical trial report
(1) General data (type of disease, total number of cases and the choice of cases); (2) clinical trial methods (settings of the control group, if necessary); (3) statistical methods and evaluation methods; (4) clinical evaluation criteria; (5) clinical trial results; (6) adverse events and side effects and their management; (7) analysis of clinical trial effect; (8) clinical trial conclusion; (9) indications, scope of application, contraindications and precautions; (10) problems and suggestions for improvement; (11) clinical trial management opinion of medical institutions responsible for clinical trials.
The results and protocols will be held strictly confidential by researchers. Publication of any data will be forbidden unless the sponsor authorizes it. The information provided by the sponsor, such as the protocols, design, results, data collection, case report forms, and informed consent documents will be kept confidential. No person, other than an authorized researcher, may access these documents.
Publication agreement of test results
Test results can be published by sponsors and authorized researchers.
The ethics committee will agree on a clinical trial to ensure the rights and interests of the participants in accordance with existing data and cognitive levels.
A clinical trial institution will have the ability to monitor and organize trials.
The investigator will ensure that all participants are fully aware of the protocol, relevant regulations, the characteristics of the medical instruments, and their responsibilities associated with the test. The investigator will ensure that the number of participants is sufficient, the participants are in accordance with the inclusion criteria, there is sufficient time in the test period, and the trial will be compliantly and securely implemented and completed.
The sponsor is responsible for the safety and authenticity of the medical device used in the trial and will ensure that all investigators conducting the trials adhere to the clinical trial protocol.
| Results|| |
Trial Status: This Trial Has Been Registered in the Chinese Clinical Trial Registry (Registration No. Chictr-Inr-17010487) on January 20th, 2017. Patient Recruitment Is Ongoing.
| Discussion|| |
Significance of this study
The ILF-TMS used in this clinical trial is a technique developed on based on TMS and the principle of biological resonance, combined with encephalofluctuography. Encephalofluctuography can be used to detect neurotransmitter changes in the brain. In addition, this approach overcomes several limitations of TMS, including its dependence on experience and the lack of theoretical guidance in strength, frequency, scheme, and efficacy evaluation. Furthermore, ILF-TMS does not require contact with the brain, is noninvasive, and safe, with low risk, and is easily accepted by patients. Therefore, ILF-TMS has great potential for clinical applications.
Advantages of this study
The Dementia Unit of the Beijing Geriatric Hospital of China was founded in 2004 and is the oldest and largest medical treatment institution for patients with dementia in China. Wide coverage of sources can ensure that sufficient participants are collected within the prescribed time. Encephalofluctuography and ILF-TMS have been used by the research team for more than 1,000 times in clinical practice, and the technician operating the equipment has considerable experience and will ensure the smooth use of ILF-TMS.
The team has long been engaged in clinical treatment and scientific research of senile dementia and has extensive experience. The evaluation scales used herein show highly consistent results across team members, ensuring the accuracy of the collection and screening.
Evidence for contribution to future studies
The trial is intended to explore a potential new approach for the treatment of behavioral and psychiatric symptoms in patients with AD. This will help to improve poor mental symptoms and the quality of life and reduce psychological and social burdens, which will greatly reduce medical costs and drug expenditure.
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ML designed the study. MLG and JHL co-designed the study. YZ assisted in designing the study. ML wrote the paper. YZ, YNG and MNC co-wrote the paper. All authors read and approved the manuscript.
Conflicts of interest
The protocols have been approved by the Ethics Committee of Beijing Geriatric Hospital of China (approval No. 2016-021). All protocols will be performed in accordance with the Ethical Principles for Medical Research Involving Human Subjects in the Declaration of Helsinki. The trial will be reported in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT). This trial has been registered in the Chinese Clinical Trial Registry (registration No. ChiCTR-INR-17010487) on January 20th, 2017. Informed consent is provided by the patient and their family after they have indicated that they fully understand the treatment plan.
Declaration of patient consent
The authors certify that they will obtain all appropriate patient consent forms. In the form, the patients will give their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Data sharing statement
No data is reported in the article.
Checked twice by iThenticate.
Externally peer reviewed.
Additional file 1: SPIRIT checklist.
[Table 1], [Table 2]