Paroxetine - Controlled Release in the Treatment of Irritable Bowel Syndrome (IBS)

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Duke University
ClinicalTrials.gov Identifier:
NCT00610909
First received: January 28, 2008
Last updated: June 19, 2013
Last verified: January 2008
  Purpose

Irritable bowel syndrome (IBS) is an extremely common disorder in the U.S population, affecting somewhere between 9-22% based on community based studies. IBS has a chronic relapsing course and overlaps with other functional gastrointestinal disorders. It accounts for high direct medical expenses and indirect costs including a significant degree of absenteeism. Most studies have suggested that there is a slight predominance among women, especially those that have suffered some form of physical or sexual trauma. It has been estimated that up to 25-40% of patients seen by gastroenterologists' are affected by IBS, and that 70-90% of these patients may have a psychiatric comorbidity, most commonly major depression and panic disorder, but also including schizophrenia, double depression, dysthymia and alcohol abuse.

Abdominal pain and disturbance of bowel habits characterize the symptoms of IBS in the absence of demonstrable structural pathology. The diagnosis of IBS relies upon clinical criteria alone, as there is no "gold standard" in laboratory findings. The diagnosis is dependent upon identifying characteristic symptoms, and then differentiating IBS from other structural bowel disorders. Previously, the diagnosis of IBS was based upon a consortium recommendation that examined and defined diagnostic criteria for over 100 functional gastrointestinal disorders. These criteria became the most definitive in the area of functional disorders and are referred to as the Rome Criteria. During the time since this consensus, these criteria have been modified, and in 1999 became the foundation for the second set of diagnostic criteria by consensus, now referred to as the Rome II criteria. The revised Rome II criteria include only the first part of the original criteria, but now require the presence of two out of three symptoms relating abdominal pain to bowel symptoms.

We designed our study and a Randomized, double-blind, parallel-group, flexible-dose, placebo-controlled 12-week study.


Condition Intervention Phase
Irritable Bowel Syndrome
Drug: Paroxetine CR
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Single-Site, Double-Blind, Flexible-Dose, Placebo-Controlled Study of the Efficacy, Tolerability, & Safety of Paroxetine - Controlled Release in the Treatment of Irritable Bowel Syndrome (IBS)

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Change from baseline in: Changes in Mean composite pain scores (on IVRS) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in Associated symptoms of IBS (diarrhea, constipation, incomplete emptying, etc.) scores IBS Quality of Life scores Clinical Global Impression scores of 1 or 2 Beck Depression Inventory II Beck Anxiety Inventory [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Recording of spontaneous adverse events throughout the screening, run-in, and treatment phases of the study Conducting the DOTES at defined points during the study [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 60
Study Start Date: January 2002
Study Completion Date: December 2002
Primary Completion Date: December 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Those in the active treatment group will receive doses of Paxil CR in increments of 12.5 mg daily for the first week and increased at 12.5 mg increments at visit weeks to a maximum of 50 mg daily, as determined by the investigator. The investigator will adjust dosage based on clinical response. Following the completion of the double-blind phase, patients on placebo and non-responders to the study drug will be tapered off the study drug back to 0 over 2 weeks, and they will be referred to their Primary Care Physician, Internist or Gastroenterologist to be prescribed treatment for Irritable Bowel Syndrome.
Drug: Paroxetine CR
Those in the active treatment group will receive doses of Paxil CR in increments of 12.5 mg daily for the first week and increased at 12.5 mg increments at visit weeks to a maximum of 50 mg daily, as determined by the investigator. The investigator will adjust dosage based on clinical response. Following the completion of the double-blind phase, patients on placebo and non-responders to the study drug will be tapered off the study drug back to 0 over 2 weeks, and they will be referred to their Primary Care Physician, Internist or Gastroenterologist to be prescribed treatment for Irritable Bowel Syndrome.
Other Name: Paxil
Placebo Comparator: 2
Same shape placebo
Drug: Placebo
Placebo

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Each patient must satisfy all the following criteria before entry into the study:

  1. Patients must have given their written informed consent to enter the study (after verification of the diagnosis criteria).
  2. Male or female patients, aged 18 to 75 years of age at last birthday.

    Female patients of child-bearing potential must use one of the following methods of contraception for the duration of the study:

    • Oral contraceptive (combined or progesterone only)
    • Parenteral progesterone-only contraceptive (e.g. Norplant®, Depo-Provera®)
    • Intra-uterine device
    • Double barrier method of contraceptive (e.g. condom plus spermicide, condom plus diaphragm, etc.) Female patients of child-bearing potential will be defined as those who are not post-menopausal or those who have not undergone a hysterectomy or surgical sterilization. (Note: to be considered post-menopausal, a woman would have to be naturally free of menses for at least 2 years).
  3. Patients presenting with Irritable Bowel Syndrome as defined by the modified Rome II Criteria:

    At least 12 weeks, which need not be consecutive, in the preceding 12 months of abdominal discomfort or pain that has two of three features:

    • Relieved with defecation; and/or
    • Onset associated with a change in frequency of stool; and/or
    • Onset associated with a change in form (appearance) of stool.

    The following symptoms cumulatively support the diagnosis of IBS:

    • Abnormal stool frequency
    • Abnormal stool form
    • Abnormal stool passage
    • Passage of mucus
    • Bloating or feeling of abdominal distention

    In order to proceed into the double-blind phase of the study, patients must have recorded at least 5 days' data for abdominal pain and Overall Assessment of symptoms on the IVRS during the placebo run-in period. In addition, the patient must demonstrate a <25% improvement in composite pain scores in placebo run-in period as compared to screening week.

  4. Patients who have experienced symptoms of IBS for a duration of greater than one year (from the date of the Screening visit) and for whom this is documented in the medical notes.
  5. Patients must be willing and able to maintain their usual diet (and, if indicated, maintain a lactose-free diet) during the course of the study.
  6. All patients must have had either a full colonoscopy or flexible sigmoidoscopy with barium enema performed at some time in the past. Additionally, they must have these procedures repeated prior to the screening visit if:

    • the patient has experienced a recent change in bowel habits (recent means within 6 months of entry to the study) or
    • the patient is aged 55 or above (at their last birthday) and has not had these investigations carried out within 5 years of entry to the study.
  7. Patients must be willing and able to comply with the study procedures.

Exclusion Criteria

A patient will be excluded from the study if any one of the following criteria applies to that patient:

  1. Patients with severe concurrent disease defined as any disease which, in the investigator's opinion, is unstable and/or life-threatening, or is serious enough to jeopardize efficacy or safety assessments during the study. This definition may include, but is not limited to:

    • Any major GI disorder (including history of inflammatory bowel disease [colitis], celiac disease, complicated colonic diverticular disease)
    • History of abdominal surgery which, in the investigator's opinion, may interfere with the assessment of IBS symptoms during the study
    • Uncontrolled diabetes
    • Uncontrolled hypertension
    • Uncontrolled thyroid disease
    • History of cancer (with the exception of basal or squamous cell carcinoma)
    • A history of any serious psychiatric disorder (including schizophrenia, bipolar disorder [including current suicidal ideation or patients who have attempted suicide within 12 months of entry to the study] and any psychiatric disorder severe enough to warrant psychiatric hospital treatment, as an in-patient within 12 months of entry to the study)
  2. Patients with current psychotic disorders, bipolar disorders, alcohol or drug dependence/abuse, anorexia nervosa or bulimia as identified by completing the Mini International Neuropsychiatric Interview at the screening visit.
  3. Patients with clinically significant abnormal blood test results at entry to the study, in the opinion of the investigator.
  4. Patients with anatomical lesions of the colon (except non-complicated diverticular disease) or microscopic colitis or inflammatory bowel disease as assessed by investigations carried out prior to the screening visit.
  5. Patients with a history of lactose intolerance prior to the screening.
  6. Patients with any history of drug or alcohol abuse in the past 6 months.
  7. Patients on antidepressants for the treatment of mood or anxiety disorders.
  8. Patients receiving any medication which may interfere with the assessment of IBS symptoms during the study, and which cannot be stopped. These medications include the following:

    • All antidepressant medication (including selective serotonin re-uptake inhibitors (SSRIs). Where antidepressant medication has been previously prescribed, the following timelines should be adhered to: a 42-day wash out period from Prozac™ (fluoxetine) before randomization into the study; a 2 week wash-out for other antidepressants.
    • Drugs with putative effect on transit (including, but not limited to, erythromycin, metoclopramide, cisapride, dicyclomine hydrochloride, hyoscyamine sulfate, etc.), anti-diarrheals (including, but not limited to dephenoloxilate with atropine, loperamide, bismuth, kaolin and pectin, etc.), and laxatives (oral or rectal). Bulking agents (including ispaghula husk, psyllium and dietary bran supplements) may be continued during the study, provided that the patient has been taking a stable dose for at lease 3 months prior to entering the study and that this dose does not change during the study. Patients taking bulking agents on an "as needed" basis must refrain from taking these medications during the study.
  9. Patients who have taken an investigational drug within 30 days (or 5 half-lives, whichever is the longer) of entry to the study, or who are due to receive such a drug during the study.
  10. Female patients who are pregnant or lactating.

The investigator should call the study monitor if he/she has any questions regarding patient eligibility.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00610909

Locations
United States, North Carolina
Department of Psychiatry Clinical Trial Team, Duke University
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Duke University
GlaxoSmithKline
Investigators
Principal Investigator: Greg Clary, M.D. Duke University
Principal Investigator: Ashwin A Patkar, M.D. Duke University
  More Information

No publications provided

Responsible Party: Greg Clary, M.D, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00610909     History of Changes
Other Study ID Numbers: 3611, IRB#3611
Study First Received: January 28, 2008
Last Updated: June 19, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
IBS

Additional relevant MeSH terms:
Irritable Bowel Syndrome
Syndrome
Colonic Diseases
Colonic Diseases, Functional
Digestive System Diseases
Disease
Gastrointestinal Diseases
Intestinal Diseases
Pathologic Processes
Paroxetine
Antidepressive Agents
Antidepressive Agents, Second-Generation
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014