Efficacy of Biofeedback in the Treatment of Tic Disorder

Efficacy of Biofeedback in the Treatment of Tic Disorder：A Randomized Controlled Trial

To investigate the efficacy of EEG biofeedback and drug therapy in the treatment of tic disorders

Study Overview

• Status: Suspended
• Conditions: Tic Disorders
• Intervention / Treatment: Device: biofeedback; Drug: Drug Aripiprazole

Detailed Description

This study intends to investigate the efficacy of EEG biofeedback and drug therapy on clinical symptoms, cognitive flexibility and quality of life in chronic tic disorder and Tourette syndrome through a randomized controlled study.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ding Qiang, master; Phone Number: 201102 18818239447; Email: johndean@foxmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201102
      • Children's hospital of Fundan University
      • Contact: Ding Qiang, master; Phone Number: 201102 18818239447; Email: johndean@foxmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 16 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Meet the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders(Fifth Edition,DSM-5) for chronic tic disorder or Tourette syndrome（TS）;
• Ethnic group is Han nationality;
• Aged 8 ~ 16 years old;
• otal IQ of Wechsler Intelligence Scale for Children ≥ 80 points for subjects;
• Symptom severity score in Yale Global Severity Scale (YGTSS), TS patients > 13, CTD > 9;
• Did not receive any drug (including traditional Chinese medicine) treatment 4 weeks before enrollment;
• Obtain written informed consent from children and guardians

Exclusion Criteria:

• Epilepsy, cardiovascular disease
• Patients with schizophrenia, mental retardation, autism spectrum disorder, bipolar disorder and major depression who meet the DSM-5 diagnostic criteria;
• Receiving systematic traditional Chinese medicine treatment one month before enrollment or currently;
• Receiving systematic psychotherapy one month before enrollment or currently;
• Receive systematic physical therapy one month before enrollment or currently
• Those who cannot follow the doctor's advice or refuse to cooperate;
• Those with obvious abnormal laboratory test results (AST or ALT ≥ 2 times of the upper limit of normal value; bun ≥ 1.5 times of the upper limit of normal value; Cr ≥ 1.2 times of the upper limit of normal value);
• Prolongation of QTc interval (QTc ≥ 450 ms in men or ≥ 470 MS in women);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biofeedback therapy; three times a week, every other day interval, 30 minutes each time, each subject received 20 biofeedback training (using the Infiniti3000A biofeedback system Patients in the theta group decreased the theta amplitude at Cz. Patients in the theta group received positive feedback when their theta activity was below the feedback threshold.	Device: biofeedback; Biofeedback therapy Biofeedback therapy, three times a week, every other day interval, 30 minutes each time, each subject received 20 biofeedback training（using the Infiniti3000A biofeedback system，Thought Technology Ltd.）.Patients in the theta group decreased the theta amplitude at Cz. Patients in the theta group received positive feedback when their theta activity was below the feedback threshold.
Active Comparator: Drug therapy; Considering the patients with chronic tic disorder (chronic motor or vocal tic disorder or Tourette's disorder), aripiprazole was selected as a single drug with constant dose during the treatment. In case of extrapyramidal side effects, benhexol was given to reduce the extrapyramidal side effects, and the dosage and duration of medication were recorded	Drug: Drug Aripiprazole; Considering the patients with chronic tic disorder (chronic motor or vocal tic disorder or Tourette's disorder), aripiprazole was selected as a single drug with constant dose during the treatment. In case of extrapyramidal side effects, benhexol was given to reduce the extrapyramidal side effects, and the dosage and duration of medication were recorded

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yale global tic severity scale	Tic symptom severity is estimated by Yale Global Tic Severity Scale Total Tic score. The YGTSS is a clinician-rated scale used to assess tic severity over the prior week. It includes a checklist of motor and vocal tics followed by an assessment of the number, frequency, intensity, complexity, and inference of motor tics and phonic tics-scored separately. Each of these dimensions is scored on a 0 to 5 scale. The YGTSS provides three tic severity scores: Total Motor (0 to 25); Total Phonic (0 to 25) and the combined Total Tic Severity Score (0 to 50), as well as a separate Impairment dimension scored from0 to 50. The Total Tic Score (YGTSS-TTS) was used in these analyses.Lower scores indicate improvement and higher scores indicate worsening.	baseline assessment (T0)
Yale global tic severity scale	Tic symptom severity is estimated by Yale Global Tic Severity Scale Total Tic score. The YGTSS is a clinician-rated scale used to assess tic severity over the prior week. It includes a checklist of motor and vocal tics followed by an assessment of the number, frequency, intensity, complexity, and inference of motor tics and phonic tics-scored separately. Each of these dimensions is scored on a 0 to 5 scale. The YGTSS provides three tic severity scores: Total Motor (0 to 25); Total Phonic (0 to 25) and the combined Total Tic Severity Score (0 to 50), as well as a separate Impairment dimension scored from0 to 50. The Total Tic Score (YGTSS-TTS) was used in these analyses.Lower scores indicate improvement and higher scores indicate worsening.	assessment after 4 weeks of treatment (T1)
Yale global tic severity scale	Tic symptom severity is estimated by Yale Global Tic Severity Scale Total Tic score. The YGTSS is a clinician-rated scale used to assess tic severity over the prior week. It includes a checklist of motor and vocal tics followed by an assessment of the number, frequency, intensity, complexity, and inference of motor tics and phonic tics-scored separately. Each of these dimensions is scored on a 0 to 5 scale. The YGTSS provides three tic severity scores: Total Motor (0 to 25); Total Phonic (0 to 25) and the combined Total Tic Severity Score (0 to 50), as well as a separate Impairment dimension scored from0 to 50. The Total Tic Score (YGTSS-TTS) was used in these analyses.Lower scores indicate improvement and higher scores indicate worsening.	assessment after 8 weeks of treatment (T2)
Yale global tic severity scale	Tic symptom severity is estimated by Yale Global Tic Severity Scale Total Tic score. The YGTSS is a clinician-rated scale used to assess tic severity over the prior week. It includes a checklist of motor and vocal tics followed by an assessment of the number, frequency, intensity, complexity, and inference of motor tics and phonic tics-scored separately. Each of these dimensions is scored on a 0 to 5 scale. The YGTSS provides three tic severity scores: Total Motor (0 to 25); Total Phonic (0 to 25) and the combined Total Tic Severity Score (0 to 50), as well as a separate Impairment dimension scored from0 to 50. The Total Tic Score (YGTSS-TTS) was used in these analyses.Lower scores indicate improvement and higher scores indicate worsening.	3-month follow-up after completion of treatment (T3).
Wisconsin Card Sorting Test	The participants were asked to sort 64 cards to match either color (red, blue, yellow, or green), form (crosses, circles, triangles, or stars), or number of figures (one, two, three, four). During the task, the sorting rule changed discreetly from color to form or number of figures without the participants being informed. The participants had to shift sets accordingly and sort cards following the new sorting rule. Set shifting difficulties were indicated by preservative errors; thus, higher scores on this test represent worse performance.	baseline assessment (T0)
Wisconsin Card Sorting Test	The participants were asked to sort 64 cards to match either color (red, blue, yellow, or green), form (crosses, circles, triangles, or stars), or number of figures (one, two, three, four). During the task, the sorting rule changed discreetly from color to form or number of figures without the participants being informed. The participants had to shift sets accordingly and sort cards following the new sorting rule. Set shifting difficulties were indicated by preservative errors; thus, higher scores on this test represent worse performance.	assessment after 4 weeks of treatment (T1)
Wisconsin Card Sorting Test	The participants were asked to sort 64 cards to match either color (red, blue, yellow, or green), form (crosses, circles, triangles, or stars), or number of figures (one, two, three, four). During the task, the sorting rule changed discreetly from color to form or number of figures without the participants being informed. The participants had to shift sets accordingly and sort cards following the new sorting rule. Set shifting difficulties were indicated by preservative errors; thus, higher scores on this test represent worse performance.	assessment after 8 weeks of treatment (T2)
Wisconsin Card Sorting Test	The participants were asked to sort 64 cards to match either color (red, blue, yellow, or green), form (crosses, circles, triangles, or stars), or number of figures (one, two, three, four). During the task, the sorting rule changed discreetly from color to form or number of figures without the participants being informed. The participants had to shift sets accordingly and sort cards following the new sorting rule. Set shifting difficulties were indicated by preservative errors; thus, higher scores on this test represent worse performance.	3-month follow-up after completion of treatment (T3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Color-word Stroop task	The Stroop task requires participants to name the ink color of a series of color words. In the congruent condition, the color name corresponds exactly to the color of each letter; in the incongruent condition, the printed word and the actual color of each letters are different. When subjects are required to report the ink color of the word, greater difficulty is experienced when they are in the incongruent condition. This difficulty can be measured by the increase in the amount of time required to complete the task (the Stroop interference effect). The measure of executive ability is the relative response delay in the Stroop interference condition as measured by response time (RT) in the incongruent condition minus RT in the neutral condition.	It's a repeated measurement variable，baseline assessment (T0), assessment after 4 weeks of treatment (T1), assessment after 8 weeks of treatment (T2), and 3-month follow-up after completion of treatment (T3)
The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS)	The CY-BOCS evaluates the severity of obsessions and compulsions, using ten items across five dimensions (time occupied by symptoms, interference, distress, resistance and degree of control over symptoms). The total severity score can range from 0 to 40. CY-BOCS total scores in the range of 14-24 are considered moderate, 25-30 moderate-severe and over 30 severe	It's a repeated measurement variable，baseline assessment (T0), assessment after 4 weeks of treatment (T1), assessment after 8 weeks of treatment (T2), and 3-month follow-up after completion of treatment (T3)
The parent version of Swanson, Nolan, and Pelham-IV(SNAP-IV)	It contains 26 items and is scored on a 0-3 Likert scale. The scale consists of three subscales, which are three parts: attention deficit, hyperactivity/impulsivity, and oppositional defiance, and can be used for the assessment of ADHD symptoms in tic symptom comorbidity in this study.	It's a repeated measurement variable，baseline assessment (T0), assessment after 4 weeks of treatment (T1), assessment after 8 weeks of treatment (T2), and 3-month follow-up after completion of treatment (T3)
Children' s Depression Inventory(CDI)	There are 27 items quantifying symptoms such as depressed mood, hedonic capacity, vegetative functions, self-evaluation, and interpersonal behaviors. Each item consists of three statements graded in order of increasing severity from 0 to 2; children and adolescents select the one that characterized their symptoms best during the past 2 weeks. The item scores are combined into a total depression score, which ranges from 0 to 54. A higher CDI score means a higher depressive state.	It's a repeated measurement variable，baseline assessment (T0), assessment after 4 weeks of treatment (T1), assessment after 8 weeks of treatment (T2), and 3-month follow-up after completion of treatment (T3)
The Screen for Child Anxiety Related Emotional Disorders(SCARED)	The SCARED is a 41-item self-report measure designed to screen for DSM-IV anxiety disorders. The SCARED includes 5 factors: somatic/panic (13 items; e.g., "When I feel frightened, it is hard to breathe"), generalized anxiety (9 items; e.g., "I worry about other people liking me"), separation anxiety (8 items; e.g., "I get scared if I sleep away from home"), social phobia (7 items; e.g., "I don't like to be with people I don"t know well"), and school phobia (4 items; e.g., "I get headaches when I am at school"). The participants rated the items of each factor on a 3-point scale (0 = not true or hardly ever true, 1 = sometimes true, and 2 = true or often true). The SCARED total score, derived by adding the responses of the 41 items, ranges from 0 to 82.	It's a repeated measurement variable，aseline assessment (T0), assessment after 4 weeks of treatment (T1), assessment after 8 weeks of treatment (T2), and 3-month follow-up after completion of treatment (T3)
Conners' Parent Rating Scale-Revised（CPRS-R）	It is suitable for children aged 3 - 16 years, and a total of 48 items in this scale include six factors: conduct problems, learning problems, psychosomatic problems, impulsive-hyperactivity, anxiety, and hyperactivity index, with a total of 48 items, which are scored on a 0-3 four-level scale.	It's a repeated measurement variable，aseline assessment (T0), assessment after 4 weeks of treatment (T1), assessment after 8 weeks of treatment (T2), and 3-month follow-up after completion of treatment (T3)
The Clinical Global Impression-severity scale	The severity of illness subscale is designed to acquaint the patient's severity of symptoms with those of other people experiencing the same mental ailment. The CGI-S rates this severity of a 1-7 scale, with (1) representing normal symptoms, meaning the patient is not ill. The highest on the scale, (7), represents patients among the most severely ill. Right in the middle at (4), a patient will be defined as moderately ill.	It's a repeated measurement variable，baseline assessment (T0), assessment after 4 weeks of treatment (T1), assessment after 8 weeks of treatment (T2), and 3-month follow-up after completion of treatment (T3)
Clinical Global Impressions-Improvement scale	The global improvement subscale allows the practitioner to create a comparative improvement based on the baseline of the first test. These changes reflect how symptoms have or have no improves due to treatment. The 7-point CGI-I scale rates improvement with a (1) representing a 'very much improved' patient and (7) representing a patient who has become 'very much worse' due to treatment. The rating (4) represents a patient displaying no change from the treatment.	It's a repeated measurement variable，assessment after 4 weeks of treatment (T1), assessment after 8 weeks of treatment (T2), and 3-month follow-up after completion of treatment (T3)

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Collaborators: Shanghai Normal University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 18, 2022
• First Submitted That Met QC Criteria: May 1, 2022
• First Posted (Actual): May 5, 2022

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: biofeedback; drug therapy; Clinical Efficacy; Cognitive flexibility
• Additional Relevant MeSH Terms: Mental Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Neurodevelopmental Disorders; Tic Disorders; Tics; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole
• Other Study ID Numbers: TD_BF_RCT20220318

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No