Clinical trial NCT03859297: Mechanisms of Rumination Change in Adolescent Depression
Official title: Developing Rumination-focused Treatment to Reduce Risk for Depression Recurrence (RDR) in Adolescence
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Major Depressive Disorder
Mood Disorders
Keywords: rumination
depression
brain imaging
cognitive behavioral therapy
rumination focused cognitive behavioral therapy
default mode network
rumination induction
Lead sponsor: Ohio State University
Sponsor class: OTHER
Collaborators: name: University of Exeter
name: National Institute of Mental Health (NIMH)
name: University of Utah
name: Nationwide Children's Hospital
name: Utah Center for Evidence Based Treatment
First posted: 2019-03-01
Enrollment: 183
Sex: ALL
Minimum age (years): 14
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: First two years. randomization to either rumination-focused cognitive behavioral therapy (RF-CBT) or Assessment only (AO) for a 10 week intervention period.

Last three years. randomization to either rumination-focused cognitive behavioral therapy (RF-CBT) or Relaxation therapy (RelaxT) for a 10 week intervention period.
Primary purpose: PREVENTION

Brief summary: This study will evaluate whether a newer treatment, rumination-focused cognitive behavioral treatment, which includes mindfulness and can be used to reduce ruminative habits, change ways in which key brain regions interact with each other (e.g.., often called connectivity), and whether these changes in habits and brain connectivity can reduce the risk for recurrence of depression in the next two years.

Detailed description: Major Depressive Disorder (MDD) is a disease that has it's onset in childhood and early adolescence for many. Treatments in adolescence tend to be acute and short-term. Unfortunately, between half and three quarters of adolescents who have a first episode of MDD will go to have a second episode within the next two years. Studies in adults suggest that maintenance treatments or preventative treatments can lower these risks and delay or stop recurrences.

The present study will use a preventative strategy, rumination-focused CBT (RF-CBT) to delay or stop the onset of another MD episode for at least two years.

For the first 2 years of the study, adolescents with a history of MDD who are currently well will be randomly selected for either treatment with RF-CBT or just treatment as usual in the first two years of the study.

In the last 3 years of the study, these adolescents will be randomized to either RF-CBT or Relaxation Therapy above and beyond TAU (Treatment as Usual). Brain, cognitive, and self-report measurements are collected before during and after the intervention to evaluate what brain and rumination changes occur, and which adolescents benefit the most from the treatment.

What will happen.

1. The Investigators determine if the child is eligible (see criteria below for 14-17 year olds with history of MDD.
2. The Investigators complete pre-intervention assessments with the child that include

   1. brain imaging
   2. tests of cognitive skills and emotion processing, including rumination
   3. questionnaires about how the adolescent thinks and responds to situations, similar questionnaires in at least one parent/guardian
   4. measurement of sleep using a handheld wristwatch (called an actigraph - optional).
3. randomization (chance assignment) in years 1-2 to either rumination focused cognitive behavioral therapy (RF-CBT) or assessment only for a 10-14 session intervention. Treatment as usual continues for all adolescents. In years 3-5, chance assignment is to RF-CBT or Relaxation Therapy.
4. repeat assessments after the intervention period. The cognitive skills and emotion processing are also assessed during the middle of the intervention period.

   1. brain imaging
   2. tests of cognitive skills and emotion processing, including rumination
   3. questionnaires about how the adolescent thinks and responds to situations, similar questionnaires in at least one parent/guardian
   4. measurement of sleep using a handheld wristwatch (called an actigraph - optional).
5. follow-up assessments to determine any changes, recurrence of depression, new treatments for the next two years.

   1. questionnaires
   2. interviews

Eligibility criteria: Inclusion Criteria:

* Previous diagnosis of Major Depressive Disorder (full or partial remission for at least two weeks) according to Diagnostic and Statistical Manual (DSM-V) criteria confirmed by the Kiddie Schedule for affective disorders (KSADSPL). Partial remission is defined as not meeting full DSM-V criteria for MDD.
* RRS score above the age and sex specific mean, T \> 50).
* 14-17 years of age at enrollment (accounting for 2 year follow-up),
* Postpubertal (Petersen Pubertal Developmental Scale)
* Youth assent and parent consent
* Intellectual Quotient (IQ) \> 75, determined by Wechsler Abbreviated Scale of Intelligence (WASI)

Exclusion Criteria:

* Endorsement of suicidality with plan or intent (assessed via KSADSPL and Children's Depression Rating Scale (CDRS-R) clinical interviews. Current or past (within previous three months) plan or intent is exclusionary.
* Lifetime history of conduct disorder, autism, any psychotic disorder (or episode unexplained by other known medical causes), or bipolar disorder. Eating disorder or alcohol/substance abuse within the previous 6 months. (Lifetime history of an anxiety disorder, disruptive mood dysregulation disorder or oppositional defiant disorder, Attention Deficit Hyperactivity Disorder (ADHD) will not be exclusionary).
* Current treatment with RF-CBT, Cognitive Behavioral Therapy (CBT), or variants thereof, or in the last 2 years. Likewise, detail oriented therapy beyond supportive therapy (e.g., homework, cognitive restructuring), in same time window (ability to recall elements of structured therapies with CBT focus).
* Metal braces or retainers, tattoos with metal, or clothing with metal fibers.
* Claustrophobia
* Current pregnancy - Parents will be asked this information at the phone screen. At the clinic eligibility visit, female participants will be asked about sexual activity in a private room separate from their parents using the pregnancy script/screen that the investigators have created. This script details that if a female is ineligible due to pregnancy or inadequate birth control, this information will not be disclosed to her parent(s). Participants who are sexually active will be asked about birth control method. Abstinence will be considered an approved form of contraception.
* Psychotropic medication outside of antidepressants such as mood stabilizers and antipsychotics will be exclusionary. Participants may have a history of current, stable antidepressant medication use, with no changes in dose for the past four weeks, no change in specific medication for six weeks.

Primary outcomes:
measure: Rumination Responsiveness Scale (RRS)
timeFrame: ~14-22 weeks
measure: Resting state functional magnetic resonance imaging (fMRI) connectivity of Default mode network to cognitive control network.
timeFrame: ~14-22 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Ohio State University
name: Scott Langenecker, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Watkins ER, Mullan E, Wingrove J, Rimes K, Steiner H, Bathurst N, Eastman R, Scott J. Rumination-focused cognitive-behavioural therapy for residual depression: phase II randomised controlled trial. Br J Psychiatry. 2011 Oct;199(4):317-22. doi: 10.1192/bjp.bp.110.090282. Epub 2011 Jul 21.
citation: Burkhouse KL, Jacobs RH, Peters AT, Ajilore O, Watkins ER, Langenecker SA. Neural correlates of rumination in adolescents with remitted major depressive disorder and healthy controls. Cogn Affect Behav Neurosci. 2017 Apr;17(2):394-405. doi: 10.3758/s13415-016-0486-4.
citation: Hvenegaard M, Watkins ER, Poulsen S, Rosenberg NK, Gondan M, Grafton B, Austin SF, Howard H, Moeller SB. Rumination-focused cognitive behaviour therapy vs. cognitive behaviour therapy for depression: study protocol for a randomised controlled superiority trial. Trials. 2015 Aug 11;16:344. doi: 10.1186/s13063-015-0875-y.
citation: Watkins ER, Nolen-Hoeksema S. A habit-goal framework of depressive rumination. J Abnorm Psychol. 2014 Feb;123(1):24-34. doi: 10.1037/a0035540.
citation: McEvoy PM, Watson H, Watkins ER, Nathan P. The relationship between worry, rumination, and comorbidity: evidence for repetitive negative thinking as a transdiagnostic construct. J Affect Disord. 2013 Oct;151(1):313-20. doi: 10.1016/j.jad.2013.06.014. Epub 2013 Jul 16.
citation: Jacobs RH, Watkins ER, Peters AT, Feldhaus CG, Barba A, Carbray J, Langenecker SA. Targeting Ruminative Thinking in Adolescents at Risk for Depressive Relapse: Rumination-Focused Cognitive Behavior Therapy in a Pilot Randomized Controlled Trial with Resting State fMRI. PLoS One. 2016 Nov 23;11(11):e0163952. doi: 10.1371/journal.pone.0163952. eCollection 2016.
citation: Dillahunt AK, Feldman DA, Thomas LR, Farstead BW, Frandsen SB, Lee S, Pazdera M, Galloway J, Bessette KL, Roberts H, Crowell SE, Watkins ER, Langenecker SA, Westlund Schreiner M. Self-Injury in Adolescence Is Associated with Greater Behavioral Risk Avoidance, Not Risk-Taking. J Clin Med. 2022 Feb 26;11(5):1288. doi: 10.3390/jcm11051288.
citation: Roberts H, Jacobs RH, Bessette KL, Crowell SE, Westlund-Schreiner M, Thomas L, Easter RE, Pocius SL, Dillahunt A, Frandsen S, Schubert B, Farstead B, Kerig P, Welsh RC, Jago D, Langenecker SA, Watkins ER. Mechanisms of rumination change in adolescent depression (RuMeChange): study protocol for a randomised controlled trial of rumination-focused cognitive behavioural therapy to reduce ruminative habit and risk of depressive relapse in high-ruminating adolescents. BMC Psychiatry. 2021 Apr 23;21(1):206. doi: 10.1186/s12888-021-03193-3.