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

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

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.

Study Overview

• Status: Completed
• Conditions: Depression; Obesity; Attention-Deficit / Hyperactivity Disorder
• Intervention / Treatment: Behavioral: Bright light therapy; Behavioral: Physical exercise

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Frankfurt am Main, Germany
    • Goethe University Hospital Frankfurt, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, and Department of Psychiatry, Psychosomatic Medicine and Psychotherapy
• Netherlands
  • Nijmegen, Netherlands
    • Radboud University Medical Centre, Karakter Child and Adolescent Psychiatry, and Department of Psychiatry
• Spain
  • Barcelona, Spain
    • Vall d'Hebron Research Institute, Group of Psychiatry, Mental Health and Addiction
• United Kingdom
  • London, United Kingdom
    • King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bright light therapy; 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; 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.; Other Names: Device: smartphone with m-Health app; Device: Philips EnergyLight HF 3419
Experimental: Physical exercise; 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; 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.; Other Names: Device: smartphone with m-Health app
No Intervention: Treatment as usual; 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?

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)

Collaborators and Investigators

• Sponsor: Goethe University
• Collaborators: King's College London; Radboud University Medical Center; Heidelberg University; Hospital Vall d'Hebron
• Investigators: Principal Investigator: Christine M Freitag, Prof. Dr., Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital, Goethe University Frankfurt am Main

Publications and helpful links

General Publications

• Mayer JS, Hees K, Medda J, Grimm O, Asherson P, Bellina M, Colla M, Ibanez P, Koch E, Martinez-Nicolas A, Muntaner-Mas A, Rommel A, Rommelse N, de Ruiter S, Ebner-Priemer UW, Kieser M, Ortega FB, Thome J, Buitelaar JK, Kuntsi J, Ramos-Quiroga JA, Reif A, Freitag CM. Bright light therapy versus physical exercise to prevent co-morbid depression and obesity in adolescents and young adults with attention-deficit / hyperactivity disorder: study protocol for a randomized controlled trial. Trials. 2018 Feb 26;19(1):140. doi: 10.1186/s13063-017-2426-1.

Helpful Links

• Homepage of the CoCA project (Comorbid Conditions of Attention-deficit / hyperactivity disorder).The PROUD study is work package 6 of the CoCA project.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2017
• Primary Completion (Actual): August 31, 2020
• Study Completion (Actual): August 31, 2020

Study Registration Dates

• First Submitted: March 3, 2017
• First Submitted That Met QC Criteria: December 7, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 14, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: exercise; depression; obesity; prevention; bright light therapy; attention-deficit / hyperactivity disorder; mobile healthy system
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Nervous System Diseases; Mood Disorders; Neurologic Manifestations; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Depression; Depressive Disorder; Obesity; Disease; Attention Deficit Disorder with Hyperactivity; Hyperkinesis
• Other Study ID Numbers: CoCA-PROUD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No