Sex Differences in Effectiveness of CBT on IBS Project 3

NCT05155631 | Completed DMC

• 2 other identifiers: IRB#20-0011181U54DK123755
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

Cognitive Behavioral Therapy (CBT) is the most well researched and most effective treatment for IBS targeting the brain-gut-microbiome (BGM) axis, and preliminary data show that this therapeutic effect is associated with a reduction of brainstem connectivity with other brain networks. The increased prevalence of IBS in women, the higher rate of comorbid non-GI pain conditions, as well as the higher prevalence in female IBS of increased sensitivity to a variety of internal and external stimuli (multisensory sensitivity) suggest the presence of important sex differences in some of these BGM mechanisms. Research performed by UCLA SCOR during previous funding has established an increased responsiveness of the CRF-Locus Coeruleus (LCC) system in female IBS subjects, suggesting that this central noradrenergic brainstem system plays an important role in IBS pathophysiology. In addition, the study team's earlier research has begun to identify clinical, functional and structural brain mechanisms that may underlie these sex effects. Based on the preliminary data, the overall goal of this project is to use CBT as a probe to study the relationship between specific disease-related alterations of the brain, the gut microbiome, and symptomatic outcome, and identify the role of sex differences in these relationships. Investigators will study male and female IBS patients before and after CBT using the advanced neuroimaging and microbiome technologies of the overall SCOR.

Conditions

IBS - Irritable Bowel Syndrome

Keywords

CBT; MRI; IBS

Outcome Measures

Primary Outcomes (1)

• Degree of connectivity between brainstem nuclei and the salience, emotional arousal and sensorimotor networks brain networks.

  Degree of connectivity between pre-drawn areas of the brainstem containing pontine nuclei and regions of the salience, emotional arousal, and sensorimotor brain networks will be quantified during a resting state functional MRI scan. The number of significant connections will be determined for pre and post treatment scans for the CBT and usual care conditions and the changes in connectivity following treatment compared for the two conditions.

  Through study completion, an average of 5 years

Secondary Outcomes (4)

• Abundance of Clostridiales taxa

  Through study completion, an average of 5 years

• Level of tryptophan metabolites

  Through study completion, an average of 5 years

• KYN/TR ratio.

  Through study completion, an average of 5 years

• Irritable Bowel Symptom Severity scale (IBSSS)

  Through study completion, an average of 5 years

Study Arms (2)

Cognitive Behavioral Treatment Arm

EXPERIMENTAL

Subjects in the "Cognitive Behavioral Treatment" Arm will undergo 8-10 weeks of remote cognitive behavioral therapy. Subjects will complete modules on their phones and will be monitored by study coordinators for support and treatment completion.

Behavioral: COGNITIVE BEHAVIORAL THERAPY

Usual Care Arm

NO INTERVENTION

Subjects in the "Usual Care" Arm will undergo 8-10 weeks of continued lifestyle. Subjects will be asked to report any new medications or lifestyle changes to study coordinators throughout the 8-10 weeks.

Interventions

COGNITIVE BEHAVIORAL THERAPY BEHAVIORAL

8-10 week self directed on line CBT program approved by FDA

Cognitive Behavioral Treatment Arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• to 55 years of age, inclusive.
• Diagnosis or symptoms of Irritable Bowel Syndrome (IBS) meeting ROME IV diagnostic criteria for IBS (all sub-types).
• Must be absent of red flags including unexplained weight loss, fevers, anemia or blood in stools.
• Females must be premenopausal menstruating females. If female and of childbearing potential must be not pregnant, post-partum or breast feeding for at least 6 months. Must have a negative urine test for pregnancy. Must be willing to avoid pregnancy and practice a non-hormonal birth control method such as abstinence, non-hormonal IUD's, or barrier method with spermicide, during the time of study enrollment. Subjects who are on hormonal based birth control (e.g OCP's or implants) will be allowed in the study as long as they still get a monthly menses so menstrual phase can be identified using ovulation kits.
• Ambulatory outpatient (not depending exclusively on a wheelchair for mobility)
• Ability to speak the English language fluently due to the standardized assessments involved.

You may not qualify if:

• Presence of a significant and ongoing medical problem that would interfere with participation in the study or testing the study hypotheses (e.g., major heart disease, neurological disorders, inflammatory diseases such as IBD; esophagitis, celiac disease, gastrointestinal malignancy or obstruction, peptic, duodenal or gastric ulcer disease, etc.). Malignancy (other than localized skin cancer that has been resected) within the previous 5 years.
• Presence of a major psychiatric diagnosis such as schizophrenia, Bipolar disorder, current ADD diagnosis, Post-traumatic Stress Disorder, Obsessive Compulsive disorder or current history of tobacco or alcohol abuse. Subjects with a history of DSMIV diagnosis of Anxiety or Depression in whom symptoms are not active, will be allowed but noted for post-hoc analysis.
• Use of investigational drugs, products or devices within 28 days prior to screen and through study participation.
• Subjects with current regular use of narcotics and or opioids. Use of centrally acting medications that will interfere with the neuroimaging testing (such as systemic steroids, opiate analgesics). Medications which alter GI motility and gastric pH will need to be stopped at least 72 hours prior to any physiologic test visit and during the baseline and treatment intervention. For this we will ask the subject to get approval from their own PCP to stop prior to any intervention. However, rescue medication of bisacodyl and loperamide will be allowed for prolonged constipation and diarrhea, respectively, during intervention periods but not during baseline or within 3 days of follow up MRI. For rescue medication, such as laxatives or antidiarrheal, we will ask to hold off use up to 3 days prior to collecting stool sample.
• Obesity (BMI \>35)
• Subjects with claustrophobia, metal implants, dental braces, large tattoos (e.g. full arm or back); making MRI safety not possible.
• History of heavy use of tobacco products or current use of more than 1/3 ppd.
• Plans to undergo a major medical intervention such a surgery within 6 months of enrollment or during the study, or had major surgery in last 6 months.
• Current or past history of chronic pain syndrome other than IBS in the IBS group (pain \>6 months at any location).
• Use of antibiotics or probiotics within 3 months of the study enrollment or regular use of probiotics within 4 weeks of enrollment. (enrollment may be deferred)
• Subjects who currently actively practice CBT or have completed a CBT therapy within 2 years prior to enrolling.
• Must must have a score of ≥175 (at least moderate severity IBS) on the IB-SSS symptom severity scale completed at screening.
• Have an average abdominal pain of at least 3 on a 0-10 point scale where 0=no pain and 10=worst imaginable pain.
• Any other condition that the investigator believes would jeopardize the safety or rights of the subject or would render the subject unable to comply with the study protocol or make use of acquired data non-analyzable.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

UCLA

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: CBT

Study Record Dates

• First Submitted: June 11, 2021
• First Posted: December 13, 2021
• Study Start: December 18, 2021
• Primary Completion: December 12, 2024
• Study Completion: January 1, 2025
• Last Updated: April 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)