Treating Comorbid Depression of Patients With Narcolepsy by Intermittent Theta Burst Stimulation

Sponsor

Chang Gung Memorial Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05884112

Collaborator

(none)

105

Enrollment

Location

Arms

27.3

Anticipated Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Narcolepsy is a chronic brain disorder. The mechanism is the impairment of brain controlling of sleep and wakefulness. The cause of this disease is still unclear, but common symptoms include excessive day time sleepiness, cataplexy, hypnogogic hallucination, sleep paralysis, and sleep disturbance. Because these symptoms are easily confused together in many situations, it is difficult for doctors to make the diagnosis. Therefore, medical treatment for patients is always delayed. According to previous research report, narcoleptic patients are often delay diagnosis for 10 to 15 years after the onset of the disease. Clearly, to make the diagnosis of narcolepsy is very difficult. Another cause for the delay is the method for diagnosing narcolepsy, which mainly rely on sleep examination instruments and the testing of hypocretin concentration in the cerebrospinal fluid. However, these tests are difficult to carry out in many areas, and diagnosing narcolepsy is still difficult in many countries. To the patients and their families, developing a fast and accurate method or tool for diagnosing narcolepsy is of the utmost importance.

Condition or Disease	Intervention/Treatment	Phase
Narcolepsy	Device: "MAGSTIM" reprtitive Transcranial Magnetic Stimulator (rTMS) System Device: sham control	N/A

Detailed Description

The purposes of this study are as follows: (1) To collect comprehensive narcolepsy and non-narcolepsy brain imaging data. The difference between the two groups will be analyzed. To find the difference between the Type 1 and Type 2 narcolepsy by brain imaging characteristics. Use these data to find the special parameter by "machine learning" and build a predictive model; (2)To collect comprehensive narcolepsy and non-narcolepsy HLA typing data. Attempt to understand the HLA profile of narcoleptic patients and their parents in Taiwan. To analyze the difference between the two groups of Type 1 and Type 2 narcolepsy. Use these data of HLA typing characteristics to find the special parameter by "machine learning" and to establish a predictive model; and (3) categorize and group narcolepsy clinical data, sleep examination data, and the aforementioned data based on machine learning concept and build a predictive model as the basis for developing a fast and accurate" narcolepsy diagnostic tool or model" in the future. Research method: This is a case control study. There are 400 subjects (age 9 - 45) will be collected. These subjects will be divided into the three following groups: (1) experimental group (narcolepsy Type 1, 200 subjects); (2) experimental group (narcolepsy Type 2, 100 subjects); and (3) control group (age and gender matched non-narcolepsy subjects, 100). The investigators will collect all the clinical data for each subject, including clinical characteristics, sleep examination data, actigraphy, HLA typing, and brain imaging data. Data analysis method: the narcolepsy clinical data, sleep examination data, and the aforementioned data were categorized and grouped through data analysis based on computer machine learning, neural network, and predictive model effectiveness analysis concepts. Then the investigators will built a predictive model based on the results.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

105 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

participant and doctor

Primary Purpose:

Treatment

Official Title:

Treating Comorbid Depression of Patients With Narcolepsy by Intermittent Theta Burst Stimulation: A Preliminary Study

Actual Study Start Date :

Feb 22, 2023

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Narcolepsy (type1 +type 2) with depression Stimulate with Double 70mm Alpha Coil figure of 8 stimulator (8-shaped stimulator) (Magstim Company, UK, high frequency magnetic stimulator with force power booster), each treatment will give subjects 1800 pulses, including 60 TBS Section stimulation, each section has 2 seconds of stimulation (30 pulses) and 8 seconds of interval, a total stimulation time of 10 minutes.	Device: "MAGSTIM" reprtitive Transcranial Magnetic Stimulator (rTMS) System iTBS is a new treatment method for depression. It uses the principle of magnetoelectricity to intermittently stimulate local brain nerves. In recent years, domestic and foreign studies have confirmed its efficacy and safety for depression. In addition, research has also It shows that iTBS has better therapeutic effect and efficiency than the previous regular rTMS.
Sham Comparator: Narcolepsy with depression Sham-control	Device: sham control sham control

Arm

Intervention/Treatment

Experimental: Narcolepsy (type1 +type 2) with depression

Stimulate with Double 70mm Alpha Coil figure of 8 stimulator (8-shaped stimulator) (Magstim Company, UK, high frequency magnetic stimulator with force power booster), each treatment will give subjects 1800 pulses, including 60 TBS Section stimulation, each section has 2 seconds of stimulation (30 pulses) and 8 seconds of interval, a total stimulation time of 10 minutes.

Device: "MAGSTIM" reprtitive Transcranial Magnetic Stimulator (rTMS) System

iTBS is a new treatment method for depression. It uses the principle of magnetoelectricity to intermittently stimulate local brain nerves. In recent years, domestic and foreign studies have confirmed its efficacy and safety for depression. In addition, research has also It shows that iTBS has better therapeutic effect and efficiency than the previous regular rTMS.

Sham Comparator: Narcolepsy with depression

Sham-control

Device: sham control

sham control

Outcome Measures

Primary Outcome Measures

Beck Depression Inventory [Screening and following up to six months.]
he Beck Depression Inventory (BDI) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression. Below 10 points are non-depressed, 10-18 are mild depression, 19-29 are moderate depression, 30-63 are severe depression.
The Beck Anxiety Inventory [Screening and following up to six months.]
a 21-question method developed by Aaron T. Beck. A multiple-choice self-administered scale designed to measure levels of clinical anxiety that can be used to measure anxiety severity. Takes 5 to 10 minutes to complete. Each answer is scored on a scale of 0 (not at all) to 3 (serious). A higher total score indicates more severe anxiety symptoms. Normalized cut-off values are: 0-7: minimal; 8-15: mild; 16-25: Moderate.

Secondary Outcome Measures

Polysomnography -SE [Screening and following up to six months.]
Change in sleep efficiency (SE, %)based on PSG during the study.
Polysomnography -TST [Screening and following up to six months.]
Change in total sleep time (TST, mins) based on PSG during the study.
Polysomnography -WASO [Screening and following up to six months.]
Change in slow wave sleep (SWS, %) based on PSG during the study.
Polysomnography -REM [Screening and following up to six months.]
Change in REM sleep (%) based on PSG during the study.
Polysomnography -SL [Screening and following up to six months.]
Change in sleep latency (SL, mins) based on PSG during the study.
Polysomnography -SWS [Screening and following up to six months.]
Change in slow wave sleep (SWS, %) based on PSG during the study.
Multiple sleep latency test [Screening and following up to six months.]
Change in Change in sleep latency (SL, mins) based on MSLT during the study.
Conners' Continuous Performance Test [Screening and following up to six months.]
The Conners Continuous Performance Test is a computer administered test that is designed to assess problems with attention.Many statistics are computed including omission errors , commission errors, hit reaction time, hit reaction time standard error, detectability, response style, perseverations , hit reaction time by block, standard error by block, reaction time by ISI , and standard error by ISI. These statistics are converted to T-scores and can be interpreted in terms of various aspects of attention including inattention, impulsivity, and vigilance.Higher rates of correct detections indicate better attentional capacity.
Wisconsin Card Sorting Test [Screening and following up to six months.]
The Wisconsin Card Sorting Test (WCST) is a neuropsychological test that is frequently used to measure such higher-level cognitive processes as attention, perseverance,working memory, abstract thinking and set shifting.
Epworth Sleepoiness Scale [Screening and following up to six months.]
Epworth Sleepoiness Scale (ESS) assesses the responder's propensity to doze or fall asleep during 8 common daily activities, such as: sitting and reading; sitting inactive in a public place; sitting and talking to someone; sitting quietly after a lunch without alcohol; or in a car, while stopped for a few minutes in traffic. An ESS score >10 suggests excessive daytime sleepiness (EDS); ESS score ≥16 suggests a high level of EDS.
Short Form-36 [Screening and following up to six months.]
36-Item Short-Form Health Survey (SF-36) includes 11 major questions that evaluate eight components (0-100), with higher scores indicating better outcome.These components include physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional wellbeing, social functioning, pain, and general health.
PET/MRI [Screening and following up to six months.]
To explore the improvement and difference of narcolepsy and depression symptoms in patients with narcolepsy comorbid depression after rTMS treatment, and to explore the pathological and physiological mechanisms.
Actigraphy-WASO [Screening and following up to six months.]
Wake after sleep onset (WASO) based on actigraphy during the study.
Actigraphy-SE [Screening and following up to six months.]
Sleep efficiency (SE, %) based on actigraphy during the study.
Actigraphy-TST [Screening and following up to six months.]
Total sleep time (TST, mins) based on actigraphy during the study.
Pittsburgh Sleep Quality Index [Screening and following up to six months.]
Nine main questions assess eight sleep components. Assessments included subjective sleep quality, time to sleep, sleep duration, sleep efficiency, sleep disturbances, use of sleeping pills, daytime dysfunction, and global Pittsburgh Sleep Quality Index scores, with higher scores indicating poorer sleep quality. Each indicator is scored between 0 and 3. The final composite score is made up of seven combined scores, with a total score ranging from 0 to 21, with lower scores representing healthier sleep quality.
Visual Analogue Scale [Screening and following up to six months.]
Assess the changes in each follow-up of daytime sleepiness and cataplexy symptoms, and the higher the score, the more severe the daytime sleepiness or cataplexy. no (0-4 mm), mild (5-44 mm), moderate (45-74 mm), and severe (75-100 mm)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Meet the diagnosis of Type 1 or Type 2 sleep disorder, and comorbid with depression.
The age is introduced between 18-60 years old, regardless of gender.
Those who agree to participate in the trial and sign the subject's consent form.

Exclusion Criteria:

Combined with epilepsy, brain injury or severe organic brain disease or serious heart disease.
Combined with serious other mental disorders, such as bipolar disorder, mental retardation or addiction disorders.
Not willing to participate in this study or not willing to fill out the consent form.
Those who are not suitable to enter the experiment after being evaluated by PI and co PI.