Trial Information

Summary: Sex Differences in Neuroendocrine and Immunologic Responses in IBS

The purpose of this study is to examine measurements of the expression of the colonic corticotrophin releasing-factor (CRF), which is a hormone responsible for stress response in relation to Irritable Bowel Syndrome. We intend to identify sex differences in the expression of the colonic CRF system, explore the relationships of the CRF system and measure of the body・s stress response and immune system. It is our intent that this study will improve our understanding of the causes of IBS, which may lead to improved treatment.

Inclusion Criteria
A subject will be eligible for inclusion in this study provided they are:

• 18-55 years of age
• Male or female
• Healthy control subjects without chronic pain disorders or IBS subjects experiencing symptoms with minimum of mild symptoms
• IBS subjects must have normal results from a flexible sigmoidoscopy or colonoscopy or a barium enema within 10 years of the screening visit, with no change in bowel habits. Endoscopic bowel evaluation in order to rule out cancer, no inflammatory bowel disease or other structural disease as determined by the subject・s ：normal； results from a flexible sigmoidoscopy (i.e., using a flexible sigmoidoscope or colonoscopy of 60 cm) after the onset of symptoms and within 10 years prior to the screening visit. IBS symptoms must have remained stable since the subject・s last flexible sigmoidoscopy or the procedure must be repeated.
• Ability to the English language fluently due to the standardized psychiatric assessments involved.
• The patient has signed and dated a written informed consent form (ICF) prior to the initiation of any study-related activities, including discontinuation of prohibited medications.
• Subjects meet the definition of IBS as defined by the ROME III symptom-based diagnostic criteria5 listed below:
  Rome III
  At least 3 months, with onset at least 6 months previously of recurrent abdominal pain or discomfort associated with 2 or more of the following:
  • Improvement with defecation; and/or
  • Onset associated with a change in frequency of stool; and/or
  • Onset associated with a change in consistency of stool

A female is eligible to enter and participate in this study is she is of:

• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal)
• Childbearing potential, has a negative pregnancy test at screen, and agrees to one of the following:
  • Oral birth control pills administered for at least one monthly cycle prior to study drug administration
  • An IUD, inserted by a qualified clinician, with published data showing that the lowest expected failure rate is less than 1% per year (not all IUDs meet this criterion)
  • Medroxyprogesterone acetate (DEPO-PROVERA) injectable contraceptive for at least 1 month prior to study entry
  • Sterilization (via hysterectomy or bilateral tubal ligation)
  • Sterilization of partner
  • Abstinence from intercourse for two weeks prior to the participation and through the testing phase
  • Use of contraceptive during sexual intercourse
• Menstrual cycle information will be obtained in all premenopausal female subjects by means of an ovulation kit.

Exclusion Criteria A subject will not be eligible for inclusion of this study is any of the following criteria apply:

• If, in the opinion of the examining physician, an unstable cardiovascular, renal, hepatic, pulmonary, endocrine, metabolic, hematologic, or gastrointestinal condition is present. In particular, patients are not eligible with a history or with symptoms of angina, irregular heart beat, history of myocardial infarction, bypass surgery, or hypertension.
• Evidence of biochemical or structural abnormality of the digestive tract; these conditions include, but are not limited to:
  • Current evidence, or history of (at any time in the past):
    • Inflammatory bowel disease (Crohn・s disease or ulcerative colitis)
    • Gastrointestinal surgery (exceptions: appendectomy, cholecystectomy, benign polypectomy, and hiatus hernia)
    • Gastroparesis
    • "Gastrointestinal malignancy
    • Gastrointestinal obstruction
    • Carcinoid syndrome
    • Chronic pancreatitis
    • Amyloidosis
  • Current evidence of (within the past 6 months):
    • Diverticulitis
    • Duodenal ulcer
    • Erosive esophagitis, any grade
    • Gastric ulcer
    • Acute pancreatitis
    • Ileus
    • Symptomatic cholelithiasis (unless the subject has had a therapeutic ERCP, or undergone a cholecystectomy)
    • Symptomatic gastroesophageal reflux disease not controlled by a stable dose of medication
• In the opinion of the investigator the subject has a concurrent illness or disability (excluding IBS) that may affect the interpretation of clinical efficacy and/or safety data, or otherwise contraindicates participation in this study (e.g., an unstable cardiovascular, renal, hepatic, pulmonary, endocrine, metabolic, gastrointestinal, hematologic, or neurological condition).
• The subject has any evidence or treatment of malignancy (other than localized basal cell, squamous cell skin cancer or cancer in situ that has been resected) within the previous 5 years.
• The control subject has a positive SCID (Structured Clinical Interview Diagnostic for DSM-IV) or a positive HAD (anxiety or depression score over 11) profile.
• The control subject has been diagnosed with a major psychiatric disorder (DSM-III-R or DSM-IV) within the past 2 years that required hospitalization and/or involved an attempted suicide (e.g., major depression, or psychoses).
• The control subject has been diagnosed post-traumatic stress disorder (PTSD).
• Current diagnosis or prior history of anorexia or bulimia nervosa.
• The subject has a history or current evidence of laxative abuse (in the clinical judgment of the physician).
• The subject has a history of alcohol or substance abuse within the previous 5 years.
• The control subject has been on any psychotropic medications (including low dose tricyclic antidepressants during the last 2 months.
  • Antipsychotic agents: risperidone (Risperdal), haloperidol (Haldol), droperidol, chlorpromazine (Thorazine), Perphenazine (Trilafon), all phenothiazines (e.g., Mellaril), quetiapine (Seroquel), olanzapine (Zyprexa), clozapine (Clozaril).
  • Antidepressants: Tricyclic antidepressants (e.g., amitriptyline [Elavil], imipramine [Tofranil], nortriptyline [Pamelor]); Selective serotonin reuptake inhibitors (e.g., fluoxetine [Prozac], sertraline [Zoloft], paroxetine [Paxil], citalopram [Celexa]); Others (e.g., venlafaxine [Effexor], trazodone [Desyrel], bupropion [Wellbutrin, Zyban]).
• The subject has been on corticosteroid agents (e.g. prednisone) in the past 6 months.
• The subject has used an investigational drug or participated in an investigational study within 30 days of screening.
• The subject refuses to discontinue one (or more) prohibited medications, specifically any narcotic (i.e. vicodin)
• The subject is a pregnant woman.
• The subject is a woman breast-feeding.
• The subject refuses or is unable to complete the self-rating questionnaires.
• Healthy controls with any history of chronic abdominal discomfort or chronic pain disorder will be excluded.
• The subject is non-ambulatory due to a neurologic disorder.

If you would like to learn more about participating in this study, please send an e-mail message using the form below.