PET/CT to Predict Response to Infliximab Therapy in Patients With Crohn's Disease

This study is currently recruiting participants.
Verified December 2012 by Brigham and Women's Hospital
Sponsor:
Information provided by (Responsible Party):
Paul Bernard Shyn, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01759017
First received: December 21, 2012
Last updated: December 24, 2012
Last verified: December 2012
  Purpose

The costs and potential complications (side effects) of therapies currently used to treat Crohn's disease could be reduced if a non-invasive test existed that determined which therapies benefit patients and which do not. A non-invasive test is a test that does not involve cutting or entering the skin. Currently, once therapies are prescribed, doctors rely solely on clinical parameters to gauge whether the therapies are helpful. This includes evaluation of overall general well-being, abdominal pain, and number of liquid stools per day. There is no established and reliable non-invasive test that can predict whether a person is responding to therapy early in the course of treatment when these evaluations may be inconclusive.

During this research study we will look for changes in sugar metabolism on low-dose PET/CT before and 2 weeks after the first infusion of infliximab therapy. This is to find out if these changes can predict clinical response and steroid-free remission at two, six and 12 months, in patients with Crohn's disease.


Condition
Crohn's Disease

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Molecular Imaging to Predict Response to Infliximab Therapy in Patients With Crohn's Disease

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • Decrease in bowel FDG-uptake from enrollment to 2 weeks [ Time Frame: one year ] [ Designated as safety issue: No ]
    Low-dose PET/CT will be performed at enrollment and at 2 weeks. Patients will be categorized as infliximab responders or non-responders based on clinical measures (overall assessment by the patient's gastroenterologist, Harvey-Bradshaw Index score, and any Crohn's-related hospitalization or surgery). We will determine if the decrease in bowel FDG-uptake is significantly different between responders and non-responders.


Secondary Outcome Measures:
  • Determination of the optimal threshold for decrease in FDG uptake on PET/CT for predicting clinical response [ Time Frame: one year ] [ Designated as safety issue: No ]
    Using ROC analysis, we will determine the optimal threshold to separate patients classified as infliximab responders or non-responders for Crohn's disease.


Estimated Enrollment: 19
Study Start Date: December 2012
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Infliximab responders
Gastroenterologist's overall assessment (response) Decrease in Harvey-Bradshaw index score of 2 or more points (clinical response) Harvey-Bradshaw index score less than 5 (clinical remission) Maintenance of steroid-free remission No Crohn's-related hospitalizations or surgeries
Infliximab non-responders
Gastroenterologist's overall assessment (no response) Decrease in Harvey-Bradshaw index score of 1 or 0 points, or increase in HBI (no response) Harvey-Bradshaw index score greater than or equal to 5 (no remission) Resumption of steroid treatment Crohn's-related hospitalization or surgery

Detailed Description:

The costs and potential complications (side effects) of therapies currently used to treat Crohn's disease could potentially be reduced if a non-invasive test existed that determined which therapies benefit patients and which do not. Currently, once therapies are prescribed, doctors rely solely on clinical parameters to gauge whether the therapies are helpful. This includes evaluation of overall general well-being, abdominal pain, and number of liquid stools per day. There is no established and reliable non-invasive test that can predict whether a person is responding to therapy early in the course of treatment when these evaluations may be inconclusive.

During this research study we will look for changes in sugar metabolism on low-dose PET/CT before and 2 weeks after the first infusion of infliximab therapy. This is to find out if these changes can predict clinical response and steroid-free remission at two, six and 12 months, in patients with Crohn's disease.

PET/CT can be used to detect active inflammation (reaction of a part of the body to injury or infection) in Crohn's disease as well as complications such as ulcers, fissures, and strictures (thinning of, breaks in, and fixed narrowing of the bowel, respectively). PET (positron emission tomography) scans take pictures using special dyes that "light up" inside the body. This happens because the special dyes contain radiation, which is similar to the radiation in a standard x-ray. CT (computed tomography) uses x-rays and a computer to make pictures.

The radioactive tracer that will be used in this study is FDG. FDG is a radioactive sugar. FDG is approved by the U.S. Food and Drug Administration (FDA). This tracer can show early response to chemotherapy or other cancer treatments for a variety of tumors. Changes in FDG uptake accurately predict persistent response in as little as hours to days after therapy has begun. These changes often happen weeks to months before anatomic changes on CT or MRI. Sometimes the CT or MRI never changes.

One of the few FDG PET studies looking at treatment for an inflammatory condition showed that FDG uptake decreased significantly within two weeks of starting therapy for rheumatoid arthritis. Accurate early assessment with FDG PET/CT shortly after starting therapy with infliximab has the potential to change the standard clinical approach to both initial and continuing infliximab therapy in patients with Crohn's disease.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Adult patients with a new diagnosis of symptomatic Crohn's disease or an established diagnosis of Crohn's disease with suspected flare. The diagnosis of Crohn's disease will be based on the combination of clinical, imaging, endoscopic, and pathology findings.

Criteria

Inclusion Criteria:

  • New diagnosis of symptomatic Crohn's disease or an established diagnosis of Crohn's disease with a suspected flare.
  • Appropriate clinical candidate for infliximab induction therapy, as determined by the patient's gastroenterologist

Exclusion Criteria:

  • Anti-TNF medications in the previous 6 months
  • Pregnancy or plan to become pregnant
  • Severe claustrophobia, sufficient to preclude PET/CT scanning
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01759017

Contacts
Contact: Paul B Shyn, MD 617-732-8353 pshyn@partners.org
Contact: Sean Cameron 617-732-8363

Locations
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
Principal Investigator: Paul B Shyn, MD Brigham and Women's Hospital
  More Information

Publications:
Responsible Party: Paul Bernard Shyn, Assistant Professor, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01759017     History of Changes
Other Study ID Numbers: 2012P000570, BWH2012P000570
Study First Received: December 21, 2012
Last Updated: December 24, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Brigham and Women's Hospital:
Crohn's disease
Inflammatory bowel disease
IBD
Infliximab
PET
PET/CT

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Infliximab
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Gastrointestinal Agents
Antirheumatic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 17, 2014