Behavioral Therapy for Crohn's Disease

Combination Therapy of Resilience Intervention With Biologics in Crohn's Disease (CATHARSIS Trial)

People living with Crohn's disease (CD) experience psychological and emotional symptoms, in addition to known chronic and disabling physical symptoms, which prevent them from living their life to the fullest (flourishing). Depression and anxiety are experienced by 30% of people living with CD and 60% of inflammatory bowel disease (IBD) patients continue to report chronic pain, stress, sleeplessness, and fatigue, even when they are "objectively" in remission. Psychological stress has been endorsed by 70% of patients with IBD as a key trigger for disease activity which is not surprising given the significance of the gut-brain-microbiome axis, the close communication between the enteric and autonomic nervous systems, and the role of the hypothalamic-pituitary axis and its neuroendocrine and immune functions in the expression of GI symptoms. Interestingly, up to 85% of patients with CD also endorse the positive impact of effective coping skills on disease course. The PI's prior work has suggested that early provision of effective coping strategies, offered at the time of diagnosis or more precisely, immediately prior to biologic medication initiation, could potentially result in faster healing and improved well-being, likely through the combination of 1) physiological mitigation of the stress response and optimization of the gut-brain-microbiome axis; and 2) promotion of effective coping and disease self-management behaviors that promote psychological flourishing despite disease. Unfortunately, to date, early effective psychosocial care has been limited by concerns over reimbursement for psychological services, access to qualified IBD mental health professionals, and the lack of a standardized methodology focused on the brain-gut stress response and how to assess, monitor, communicate and maintain tight control over both physical and emotional well-being. CATHARSIS is a rigorous, placebo-controlled, randomized controlled trial of coping strategies plus medication for 170 people living with Crohn's for less than 5 years who are about to start a new biologic medication due to active disease. Outcomes include improvements in emotional well-being as well as clinical and endoscopic remission over a 12-month period. The overall goal of the study is to demonstrate that it is essential to combine biologic therapy and psychosocial care to ensure optimal and long-term positive outcomes in CD.

Study Overview

• Status: Recruiting
• Conditions: Crohn's Disease
• Intervention / Treatment: Behavioral: Primary Intervention for Combination Therapy - IBD Coping Strategies Program; Behavioral: Time and Attention Control - IBD Support Program

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laurie Keefer, PhD; Phone Number: 212-824-7770; Email: laurie.keefer@mssm.edu
• Study Contact Backup: Name: Candela De Amorrortu; Phone Number: (857) 259-7585; Email: candela.deamorrortu@mssm.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Principal Investigator: Laurie Keefer, PhD
    • New York, New York, United States, 10128
      • Recruiting
      • New York Gastroenterology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults (18-65 years old) of any sex, gender, and racial/ethnic background with an endoscopically and histologically confirmed CD diagnosis will be eligible.
• Participants must have active CD symptoms as defined by a Crohn's Disease Activity Index (CDAI) of at least 220 and
• Active endoscopic inflammation defined as a Simple Endoscopic Score for CD (SES-CD) > 6 (or ≥4 for isolated ileal disease) on most recent colonoscopy OR active disease on imaging study OR elevated calprotectin/CRP levels
• Must be planning to start an anti-TNF (adalimumab, certolizumab, or infliximab) or anti-IL-23 (risankizumab, guselkumab, mirikizumab) within the prior 2 weeks or in the next 6 weeks.
• Participants will need to live in one of Dr Keefer's 30+ PSYPACT licensed states.

Exclusion Criteria:

• Endoscopically inactive Crohn's disease at baseline.
• Unable to consent to participation.
• Pregnant or planning to become pregnant in next 12 months.
• Severe psychiatric symptoms.
• Surgical history for CD.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primary Intervention for Combination Therapy - IBD Coping Strategies Program; This 7-session protocol is based on Dr. Keefer's validated Project Management for Crohn's disease treatment manual. The program specifically focuses on reducing stress, building resilience, fostering self-confidence and disease acceptance, all of which have been associated with improved adjustment to disease and better self-management outcomes in CD.	Behavioral: Primary Intervention for Combination Therapy - IBD Coping Strategies Program; psychosocially credible treatments each comprised of seven 45-minute sessions over a 12-week period, delivered via telemedicine.
Sham Comparator: Time and Attention Control Group - IBD Support Program (Standard Therapy); This 7-session condition will serve as a Time and Attention Control to the Coping Strategies Program. The therapist will follow Dr. Keefer's previously validated control condition manual focused on supportive listening, disease education and self-reflection.	Behavioral: Time and Attention Control - IBD Support Program; psychosocially credible treatments each comprised of seven 45-minute sessions over a 12-week period, delivered via telemedicine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The PROMIS Global Health Scale	Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Scale A series of person-centered measures that evaluate and monitor physical, mental, and social health in adults and children. 10-item patient-reported questionnaire. standardized to the general population, using the "T-Score". The average "T-Score" for the United States population is 50 points, with a standard deviation of 10 points. Higher scores indicate a healthier patient.	at week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychological Well-Being Scale	Each item uses a 7-point scale (1=strongly agree; 7=strongly disagree) There are 6 subscales: The Autonomy subscale, The Environmental Mastery subscale, The Personal Growth subscale, The Positive Relations with Others subscale, The Purpose in Life subscale, and The Self-Acceptance subscale. Subscales scored from 3 to 21, with higher score indicating higher levels of psychological well-being. Full scale from 18 to 126, with higher score indicating higher levels of psychological well-being.	at weeks 12, 24, 36 and 52
Inflammatory Bowel Disease Self-Efficacy Scale (IBD-SES)	The IBD-SES is a 13-item questionnaire. Each item scored 1 (completely disagree) to 5 (completely agree). The IBD-SES assesses how patients manage things related to their IBD and other things in their everyday life. For each statement, they must select the number that best fits the answer for the past two weeks. Full scale from 13-65 with higher score indicating better health outcomes.	at weeks 12, 24, 36 and 52
NIH PROMIS-29	Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) measures seven domains: depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and the ability to participate in social roles and activities. Each domain has 4 questions ranked on a 5-point scale, and refer to the 7 previous days except physical function which has not time frame. Scoring is standardized to the general population, using the "T-Score". The average "T-Score" for the United States population is 50 points, with a standard deviation of 10 points. Higher scores indicate poorer health outcomes for anxiety, depression, fatigue, ability to participate in social roles and activities, and pain interference domains. Lower scores reflect worse outcomes for physical function and sleep disturbances domains.	at weeks 12, 24, 36 and 52
Crohn's Disease Activity Index (CDAI)	Crohn's Disease Activity Index (CDAI) score is a measurement of the severity of the Crohn's disease symptoms. Full scale ranges from 0-600, with higher score indicating more severe disease.	at weeks 12, 36, and 52
Patient-Reported Outcomes (PRO2)	The PRO2 questionnaire assesses stool frequency and rectal bleeding, each question scored from 0-3. Full scale from 0-6, with higher score indicating poorer health outcomes.	at weeks 12, 24, 36, and 52
Inflammatory Bowel Disease Questionnaire (IBDQ)	Inflammatory Bowel Disease Questionnaire (IBDQ) is a 32 item questionnaire. Full scale from 32-224, with higher score indicating better quality of life.	at weeks 12, 24, 36, and 52
UCLA GI Symptom Severity Score	UCLA GI Symptom Severity Score rates overall severity of GI symptoms. Full scale from 0-20, with higher score indicating more intense symptoms.	at weeks 12, 24, 36, and 52
Simple Endoscopic Score for Crohn's Disease (SES-CD)	Simple Endoscopic Score for Crohn's Disease (SES-CD) is used to quantify and compare inflammatory load. The Simple Endoscopic Score for Crohn Disease (SES-CD) assesses the size of mucosal ulcers, the ulcerated surface, the endoscopic extension and the presence of stenosis. Each item is scored from 0-3, with total score from 0-60. Higher score indicates poorer health.	at 24 weeks
C-reactive protein level	C-reactive protein (CRP) is produced by the liver. The level of CRP rises when there is inflammation in the body. It is one of a group of proteins, called acute phase reactants that go up in response to inflammation. The levels of acute phase reactants increase in response to certain inflammatory proteins called cytokines. These proteins are produced by white blood cells during inflammation. The CRP test is a general test to check for inflammation in the body. It is not a specific test. This means it can reveal inflammation somewhere in the body, but it cannot pinpoint the exact location or reason.	up to 24 weeks
fecal calprotectin level	Inflammatory markers measured in stool samples can be used for assessing the disease in patients who have undergone surgery. A stool test called fecal calprotectin can be of help in determining if symptoms are indicative of a flare-up of disease.	up to 24 weeks

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: The Leona M. and Harry B. Helmsley Charitable Trust
• Investigators: Principal Investigator: Laurie Keefer, PhD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Ryan Ungaro, MD, MS, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: July 15, 2024
• First Submitted That Met QC Criteria: July 19, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease; Physical Phenomena; Time
• Other Study ID Numbers: STUDY-24-00338

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No