Prevention of Comorbid Depression and Obesity in Attention-deficit/ Hyperactivity Disorder

Study Overview
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Brief Summary
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Depression and obesity are very common among adolescents and young adults with attention-deficit/ hyperactivity disorder (ADHD). However, intervention programmes to prevent these comorbid disorders rarely exist. In a pilot randomized-controlled study we test two newly developed intervention programmes that do not involve medication: bright light therapy and physical exercise. Both interventions will be supported by a mobile Health application to monitor and feedback intervention success and booster patients' motivation.

Detailed Description
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The risk for comorbid major depressive disorder and obesity is increased in adolescents and adults with attention-deficit/ hyperactivity disorder (ADHD), and adolescent ADHD predicts adults major depressive disorder and obesity. Nonpharmacological interventions to prevent these comorbidities are urgently needed. Bright light therapy (BLT) improves day-night rhythm and is an established therapy for major depression in adolescents and adults. Exercise prevents and reduces obesity in adolescents and adults and also improves depressive symptoms. Interestingly, a reinforcement-based intervention using a mobile health app (m-Health) resulted in improved effects on weightloss in obesity. The aim of the current pilot randomized-controlled phase-IIa study is to establish feasibility and effect sizes of two kinds of interventions, BLT and exercise, in combination with m-Health based monitoring and reinforcement in adolescents and young adults aged 14 to 45 years old with ADHD, targeting the prevention of depressive symptoms and obesity. In addition, immediate and long-term treatment effects on ADHD specific psychopathology, health related quality of life, fitness and body related measures, neurocognitive functions and chronotype are explored. Furthermore, saliva samples are taken in a subgroup of adult patients to explore the effects of BLT and exercise on concentrations of hormones. This subgroup of adult patients will also participate in an additional neuroimaging study of the reward system in order to explore intervention effects on striatal reward reactivity.

Official Title
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Pilot Randomized-controlled Phase-IIa Trial on the Prevention of Comorbid Depression and Obesity in Attention-deficit/ Hyperactivity Disorder

Conditions
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Attention-Deficit / Hyperactivity Disorder, Depression, Obesity

Intervention / Treatment
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* Behavioral: Bright light therapy
* Behavioral: Physical exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ADHD according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria Stable treatment as usual comprising pharmacotherapy, group based or individual cognitive behavioural therapy (not including elements of bright light therapy or exercise) Exclusion Criteria: Intelligence Quotient (IQ) below 75 Any severe (comorbid) psychiatric disorder with necessary additional psychopharmaco or daycare/ inpatient therapy beyond treatment as usual Severe medical/ neurological condition not allowing bright light therapy or exercise History of epilepsy Use of antipsychotics, antiepileptic or photosensitising medication Substance abuse/ dependency

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 45 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
Interventional Model Description: Prospective, randomized, observer-blinded, controlled, multi-centre, pilot phase-IIa parallel-group design with three arms (two treatment groups and one control group); three trial phases: baseline assessment, 10 weeks of treatment versus treatment as usual; 12 weeks post-treatment observation period.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bright light therapy<br>Mobile therapeutic light (10.000 LUX), daily (except Sunday) for 30 min in the morning or evening for 10 weeks in total. Additional treatment as usual comprising pharmacotherapy, group based or individual cognitive behavioural therapy (not including elements of bright light therapy or exercise) is allowed. | Behavioral: Bright light therapy<br>* Mobile therapeutic light (10.000 LUX, white light without UV light), daily (except Sunday) for 30 min in the morning or evening for 10 weeks in total at home provided by a bright light therapy device (Philips EnergyLight HF 3419). Monitoring and feedback will be realized with the m-Health system comprising of a smartphone equipped with the m-Health App, and an activity sensor equipped with a light sensor to monitor the light exposure of the participant.<br>* Other names: Device: Philips EnergyLight HF 3419;|
| Experimental: Physical exercise<br>Aerobic exercise of moderate-to-vigorous intensity three days a week plus muscle-strengthening exercises two days a week during 10 weeks in total. Additional treatment as usual comprising pharmacotherapy, group based or individual cognitive behavioural therapy (not including elements of bright light therapy or exercise) is allowed. | Behavioral: Physical exercise<br>* During 10 weeks participants perform three days of aerobic activities proposed and in two of these days also do muscle-strengthening exercise. Specifically, a training day consists of: (i) a 5-min warm-up period, (ii) a 10-35 min of muscle-strength training on two of the three days, (iii) a 20-40 min of aerobic training, (iii), and a 5-min of flexibility/stretching cool-down. During the course of the 10 weeks, the duration and intensity of the exercises will increase gradually. Instruction, monitoring, and feedback will be realised by the m-Health system including a smartphone equipped with the m-Health app and Secure Digital Memory cards to store the exercise videos as well as an activity sensor equipped with a mobile sensor for the acquisition of physical activity.<br>* Other names: Device: smartphone with m-Health app;|
| No Intervention: Treatment as usual<br>Stable treatment as usual comprising pharmacotherapy, group based or individual cognitive behavioural therapy (not including elements of bright light therapy or exercise). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in clinician-rated depressive symptoms (observer-blinded assessment) | Inventory of Depressive Symptomatology (clinician-rated) | baseline, end of intervention (10 weeks after baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in clinician-rated depressive symptoms (observer-blinded assessment) | Inventory of Depressive Symptomatology (clinician-rated) | baseline, follow up (22 weeks after baseline) | 
| Change from baseline in clinician-rated ADHD symptoms | ADHD Rating Scales for adults and children | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in self-reported severity of depressive symptoms | Beck Depression Inventory II | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in self-reported health status | Health Questionnaire EQ-5D-3L | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in self-reported health related quality of life | Short Form Health Questionnaire General Health Questionnaire | baseline, end of intervention (10 weeks after baseline) | 
| Change from baseline in self-reported general health status | General Health Questionnaire General Health Questionnaire | baseline, end of intervention (10 weeks after baseline) | 
| Change from baseline in self-reported emotional and behavioural problems in adolescents | Youth self-report | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in self-reported emotional and behavioural problems in adults | Adult self-report | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in circadian rhythm | Munich Chronotype Questionnaire | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in cognitive emotion regulation | Cognitive Emotion Regulation Questionnaire | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in neurocognitive functions: verbal memory | Rey Auditory Verbal Learning Test | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in neurocognitive functions: Digit span | Digit span | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in self-reported physical fitness | International Fitness Scale | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in general muscular fitness | handgrip strength test | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in muscular fitness | standing long jump test | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in aerobic fitness | Chester step test | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in body mass index | body mass index measured by clinician | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in waist circumference | waist circumference measured by clinician | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in waist-to-hip ratio | waist-to-hip ratio measured by clinician | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in body fat percentage | based on skinfold thickness measurements using a skinfold caliper | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in heart rate | heart rate measured by clinician | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in blood pressure | blood pressure measured by clinician | baseline, end of intervention (10 weeks after baseline), follow-up (22 weeks after baseline) | 
| Change from baseline in number of steps | number of steps measured with the mobile Health app | baseline, end of intervention (10 weeks after baseline) | 
| Change from baseline in movement acceleration | movement acceleration measured with the mobile Health app | baseline, end of intervention (10 weeks after baseline) | 
| Change from baseline in sleep time | sleep time measured with the mobile Health app | baseline, end of intervention (10 weeks after baseline) | 
| Change from baseline in context parameters | context measured with the mobile Health | baseline, end of intervention (10 weeks after baseline) | 
| Change from baseline in mood regulation | mood regulation measured with the mobile Health app | baseline, end of intervention (10 weeks after baseline) | 
| Change from baseline in reward reactivity | reward reactivity measured with the mobile Health app | baseline, end of intervention (10 weeks after baseline) | 
| Change from baseline in stress reactivity | stress reactivity measured with the mobile Health app | baseline, end of intervention (10 weeks after baseline) | 
| Change from baseline in inattention | inattention measured with the mobile Health app | baseline, end of intervention (10 weeks after baseline) | 
| Change from baseline in melatonin concentration | Saliva sample will be taken to measure melatonin concentration | baseline, end of intervention (10 weeks after baseline) | 
| Change from baseline in cortisol concentration | Saliva sample will be taken to measure cortisol concentration | baseline, end of intervention (10 weeks after baseline) | 
| Change from baseline in leptin concentration | Saliva sample will be taken to measure leptin concentration | baseline, end of intervention (10 weeks after baseline) | 
| Change from baseline in ghrelin concentration | Saliva sample will be taken to measure ghrelin concentration | baseline, end of intervention (10 weeks after baseline) | 
| Change from baseline in neural activity associated with reward processing | Striatal functional magnetic resonance imaging signal related to reward processing | baseline, end of intervention (10 weeks after baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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attention-deficit / hyperactivity disorder, depression, obesity, prevention, bright light therapy, exercise, mobile healthy system