The Effect of Exercise on Preventing Depression in Young People

Study Overview
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Brief Summary
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It is estimated that approximately 30% of child and adolescents manifest subthreshold depression, which can further develop into major depression with as high as 25%-50% within one year. The main aim of this trial is to investigate the effect of long-term exercise on preventing major depression and depressive symptoms in young people (aged 10-17 years old). Other aims include the underlying mechanisms of how aerobic exercise works and predictors for treatment response.

Detailed Description
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This is multi-center, psycho-education randomized controlled trial, consisting of two periods with each of 6 months (i.e supervised and maintenance period). In the exercise intervention arm, during the first 6 months, participants will be asked to do moderate-intensity aerobic exercise 3-4 times a week, which will be supervised in person by physical educators/professionals. In the next 6-month maintenance period, participants will be asked to continue doing aerobic exercise at the same intensity and frequency, which will not be supervised in person by educators/professionals, but they will be sent reminders and report adherence weekly. All of the physical activity will be recorded by accelerometer at scheduled time points (e.g. the first week, 6 week, 3 month, 6 month, 9 month, 12 month). Psycho-education group will be given 6 sections of general psycho-education onsite and/or virtually dependent on the surroundings with regards to the impact of the COVID-19 pandemic. The main aim of this trial is to investigate the effect of long-term aerobic exercise on prevention depression in young people with subthreshold depression.

Official Title
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A Multi-center， 12-month，Parallel-group, Randomised Controlled Exercise Trial in Young People With Subthreshold Depression

Conditions
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Major Depression, Subthreshold Depression, Exercise

Intervention / Treatment
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* Behavioral: Aerobic exercise intervention
* Behavioral: Psycho-education


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: There are two or more Diagnostic and Statistical Manual of Mental Disorder (DSM)-5 depressive symptoms, including at least one core symptom. Any of the core symptoms of subclinical depressive syndrome lasts at least one week, with symptom manifestation ≥50% of the time. CES-DC ≥16 points, Altman Self-Rated Mania Scale (ASRM) < 13 points. 10 17 years old. Exclusion Criteria: Current or past DSM-5 criteria for major depressive disorder,Bipolar disorder, Schizophrenia. With moderate or above suicide risk determined by Columbia-Suicide Severity Rating Scale (C-SSRS) (who will be referred to psychologist and/or psychiatrist for follow-up intervention) Musculoskeletal problems such as arthritis, gout, osteoporosis, or back, hip or knee pain that may interfere with exercising A history of organic brain disease or brain trauma Alcohol, drug or other psychoactive substance abuse or dependence Currently enrolled in another exercise study Any condition that would make exercise unsafe or unwise Taking medication that interferes with heart rate response to exercise such as beta blockers

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic Exercise<br>The whole exercise lasts for 12 months, consisted of 6-month supervised exercise and 6-month maintenance period. It is moderate -intensity exercise (60-80% Maximum heart rate), each time last for 30 mins (plus 10-minutes for warm-up and cool-down), 3-4 times a week, for the first six months, which will be supervised in person by physical educators and/or physical professionals. In the maintenance period, participants are asked to exercise at the same intensity and frequency, but will not be supervised in person by physical educators/professionals. They will receive reminder on a weekly basis and their physical activities be recorded by accelerometer. Types of exercise will be chosen according to individual school's facility and feasibility, including jogging, fast walking, badminton, running, football etc. | Behavioral: Aerobic exercise intervention<br>* The whole exercise lasts for 12 months, consisted of 6-month supervised exercise and 6-month maintenance period. It is moderate -intensity exercise (60-80% Maximum heart rate), each time last for 30 mins (plus 10-minutes for warm-up and cool-down), 3-4 times a week, for the first six months, which will be supervised in person by physical educators and/or physical professionals. In the maintenance period, participants are asked to exercise at the same intensity and frequency, but will not be supervised in person by physical educators/professionals. They will receive reminder on a weekly basis and their physical activities be recorded by accelerometer. Types of exercise will be chosen according to individual school's facility and feasibility, including jogging, fast walking, badminton, running, football etc.<br>|
| Placebo Comparator: Psycho-education<br>It consists of 6 sections of psycho-education, with topics covering mood regulations and mental well-being. Approximately 1 section in every two months. | Behavioral: Psycho-education<br>* It consists of 6 sections of psycho-education, with topics covering mood regulations and mental well-being. Approximately 1 section in every two months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Onset of Major depressive Disorder (MDD) | Kiddie-Sads-Present and Lifetime Version (K-SADS-PL) | month 6 and month 12 | 
| Changes from baseline in CES-DC at month 6 | Center for Epidemiological Studies Depression Scale for Children (CES-DC) is a self rating scale and has been shown to be effective in groups aged 6-23. CES-DC is used to measure the depressive severity；its measured time range is within the past week. In this study, version of 20-items is used. The higher the score indicates the more severe the depression symptoms, the scale author recommends 15 points as the screening demarcation value. | month 6 and month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cognitive function from baseline | Cognitive function is measured by THINC-it tool, a tool for cognitive assessment. | Month 3,6 and month 12 | 
| Levels of inflammatory biomarkers from baseline | inflammatory biomarkers (IL-6, CRP etc) will be analyzed using ELISA | Month 3, 6 and month 12 | 
| Brain structural and functional changes over time | Multimodal 3T MRI will be used | month 3,6, or 12 | 
| Occurrence of Non-suicidal self-injury and suicidal behavior |  | Month 6 and month 12 | 
| Physical activity level | The International Physical Activity Questionnaire - Short Form (IPAQ - SF) will be used to assess physical activity level | Month 6, 9 and 12 | 
| Electroencephalograph (EEG) scalp signal changes over time | Brain activity will be measured by the EEG | Month 3, 6 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subthreshold depression, aerobic exercise, Major depression, Intervention