Understanding and Treating Neuropsychiatric Symptoms of Pediatric Physical Illness

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2008 by University of Pittsburgh.
Recruitment status was  Recruiting
Information provided by:
University of Pittsburgh
ClinicalTrials.gov Identifier:
First received: March 24, 2008
Last updated: October 7, 2008
Last verified: October 2008

This research will examine the impact of brain activity, cognitive processing immune functioning, and gastrointestinal functioning on depressive symptoms and response to a psychotherapeutic intervention in youths with Inflammatory Bowel Disease (IBD).

Condition Intervention
Inflammatory Bowel Disease
Ulcerative Colitis
Crohn's Disease
Behavioral: Primary and Secondary Coping Enhancement Training
Behavioral: Supportive Non-directive Therapy

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Understanding and Treating Neuropsychiatric Symptoms of Pediatric Physical Illness

Resource links provided by NLM:

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Childhood Depression Rating System- Revised (CDRS-R) [ Time Frame: Baseline, 3 months, 9 months, 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • KVID- Subjects will be shown a series of words and asked to identify the valence of the words as positive, negative or neutral. [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • CuedRT: This standard cognitive task will be used to obtain a baseline measure of cognitive activity. The mask of X's will be replaced by a string of a's. Youth are asked to hit a button as soon as a's appear on the screen. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Virtual Reality Navigation Task: Subjects will be asked to use a computer to navigate through a virtual reality city, looking for specific locations. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Functional Magnetic Resonance Imaging (fMRI) brain scan [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Measurements of Pupil Dilation (concurrent with fMRI scan) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Laboratory Measurement for inflammatory markers- blood draws will be utilized to measure erythrocyte sedimentation rate, C-reactive protein, hematocrit, and albumin, and saliva samples will be obtained to assess salivatory cortisol [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Pediatric Crohn's Disease Activity Index (PCDAI) completed by the physician [ Time Frame: Basline, 3 months, 9 months, 12 months ] [ Designated as safety issue: No ]
  • Pediatric Ulcerative Colitis Activity Index (PUCAI) completed by physician [ Time Frame: Baseline, 3 months, 9 months, 12 months ] [ Designated as safety issue: No ]
  • Childhood Depressive Inventory (CDI) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Schedule for Affective Disorders and Schizophrenia- Kiddie version (KSADS) [ Time Frame: Baseline, 3 months, 9 months, 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: January 2008
Estimated Study Completion Date: September 2012
Estimated Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PASCET-PI Behavioral: Primary and Secondary Coping Enhancement Training
A cognitive behavioral therapy designed to help individuals cope with physical illness.
Active Comparator: SNDT Behavioral: Supportive Non-directive Therapy
A non-structured therapy designed to provide a supportive atmosphere in which individuals may discuss concerns and process events in their lives

Detailed Description:

Depression is costly, worsens morbidity and mortality, and has detrimental effects on disease course in physically ill populations. This research takes a novel multi-dimensional approach to assess the neurobiological basis of depression in chronic pediatric physical illness using inflammatory bowel disease (IBD) as a model. It also evaluates the efficacy of a modified cognitive behavioral therapy (CBT) on emotional well-being, physical health, economic costs, and neurobiological outcomes. These results will provide key building blocks for a paradigm shift within medicine by integrating behavioral health into the comprehensive medical care of physical illnesses.

Little is known about how the brain and body interact to increase depressive vulnerability, particularly in youth. Adult studies identify disruptions in limbic and prefrontal brain activity in the pathophysiology of depression. Cytokines secondary to inflammation and exogenous treatment with steroids can cause mood and cognitive changes in these same brain regions. It is important to understand the neuropsychiatric effects of IBD and its treatment on underlying brain structures during adolescence, a critical developmental period for brain maturation underlying emotional regulation and cognitive processing. More importantly, neuronal plasticity during adolescence may still allow reversibility of disease-related brain effects through teaching coping strategies for life-long illness management that could change developmental trajectories and reduce vulnerability in adulthood.

Using translational neuroscience approaches, this research will examine: 1) brain regions that underlie emotional and cognitive processing in youth with active IBD and depression using brain functional magnetic resonance imaging compared to youth with IBD and no depression, and normal controls; 2) the inter-relationship between depressive symptoms in IBD and brain, immune, and gastrointestinal functioning; and 3) efficacy of a combined CBT-physical illness narrative intervention targeting emotional and cognitive processing compared to supportive non-directive therapy in the depressed IBD cohort with longitudinal tracking of emotional, physical health, economic, and neurobiological outcomes.


Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

Inclusion criteria for youths with IBD for Step 1 of Screening Process:

  • Age 12 to 17 inclusive
  • English-speaking
  • Capable of completing CDI
  • Meeting diagnostic criteria for IBD
  • Absence of mental retardation by history
  • Having at least one appointment at the GI clinic.

Criteria for Classification of IBD:

  1. Presence of appropriate history: abdominal pain, chronic diarrhea, bloody diarrhea (with or without extraintestinal symptoms) or, less commonly, a) primary extraintestinal symptoms, b) growth retardation, c) peri-rectal abscess, or d) acute abdomen.
  2. Evidence of colitis, ileitis or granulomatous esophagitis, gastritis or duodenitis by biopsy and/or small bowel strictures or fistulas by X-ray or multiple small intestinal ulcerations by capsule endoscopy.

Eligibility Criteria For youths with IBD for Intervention Phase of the Comparison Study

Inclusion Criteria:

  1. CDI or CDI-P > 10 at Step 1
  2. CDRS-R > 34 at Step 2
  3. Presence of at least one biological parent. Exclusion Criteria

1. History or current episode of bipolar disorder, eating disorder, or psychotic disorder by DSM-IV criteria. 2. Recent suicide attempt (within 1 month of study entry) or depression severity requiring acute psychiatric hospitalization within 3 months of study entry. 3. Antidepressant medications within one month of assessment. 4. Substance abuse by history within 1 month of study entry. 5. Current treatment with CBT or failure of previous CBT trial for depression judged adequate by at least 12 treatment sessions over a period of less than 1 year conducted by an appropriately trained mental health provider using a manual. If currently receiving other psychotherapy modalities, willingness to suspend treatment for 12-week acute treatment phase of study.

Physically Healthy Comparison Children

Inclusion Criteria:

  • Age 12 to 17 inclusive
  • English-speaking
  • Capable of completing CDI
  • Absence of mental retardation by history

Exclusion Criteria:

  • self-report of a cold, flu or other infection within the past two weeks
  • self-reported use of any antibiotics within the past 2 weeks
  • score of 6 or more on the blood draw screening questionnaire

Screening process for youths with IBD: Participants will be recruited from the clinic through a 2-step screening of all consecutive pediatric patients seen in the IBD clinic or while medically hospitalized for an IBD flare-up at Children's Hospital of Pittsburgh, who have confirmed IBD and who meet the other eligibility criteria as determined by medical staff in IBD clinic (Tables 5 and 6). The medical diagnosis of IBD will be determined by a GI physician using criteria below and will be confirmed in the medical record. Step 1: administration of the CDI and CDI-P during the medical visit. Those subjects whose CDI and/or CDI-P score of > 10 will be invited by phone to participate in Step 2: a face to face interview. This cut-off score was chosen as it is consistent with an adjustment disorder (Kovacs, 1992); it is consistent with sub-clinical levels of depression that are not solely from neurovegetative symptoms and; because it still provided an adequate range of scores to detect improvement in our preliminary work. Step 2 assessment will be conducted within one week of Step 1 so that both CDI score and IBD severity ratings are still valid from the Step 1 screen.

All subjects meeting eligibility criteria for Step 2 will be invited to participate in the completion of neuropsychiatric questionnaires, blood draw, pupil measurements, and brain functional magnetic resonance imaging within one week of Step 1.

All subjects meeting eligibility criteria after Step 2 (Table 7) will be invited to participate in the treatment phase of the study. See Human Subjects Section for more details about screening and consent procedures. All subjects who choose not to participate or dropout of treatment for any reason will be referred for a psychiatric evaluation in the Psychiatry Department. The face to face assessment in Step 2 will consist of assessments both parent and child report. Subject and parent burden will be approximately 3-3.5 hours.

Normal controls (N=15) will be recruited from the Department of Pediatrics during outpatient clinical office visits.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00769353

Contact: Eva M Szigethy, MD, Ph.D. 412-692-9147 szigethye@upmc.edu

United States, Massachusetts
Children's Hospital of Boston Recruiting
Boston, Massachusetts, United States, 02115
United States, Pennsylvania
Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
Principal Investigator: Eva M Szigethy, MD, Ph.D. University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh
  More Information

No publications provided

Responsible Party: Dr. Eva M. Szigethy, University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh
ClinicalTrials.gov Identifier: NCT00769353     History of Changes
Other Study ID Numbers: DP2 OD001210-01
Study First Received: March 24, 2008
Last Updated: October 7, 2008
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Colitis, Ulcerative
Crohn Disease
Depressive Disorder
Inflammatory Bowel Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Behavioral Symptoms
Mood Disorders
Mental Disorders
Pathologic Processes

ClinicalTrials.gov processed this record on April 23, 2014