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

NCT00610909 | Completed Phase 4

• 2 other identifiers: 3611IRB#3611
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Irritable Bowel Syndrome

Keywords

IBS

Outcome Measures

Primary Outcomes (1)

• Change from baseline in: Changes in Mean composite pain scores (on IVRS)

  12 weeks

Secondary Outcomes (2)

• 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

  12 weeks

• 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

  12 weeks

Study Arms (2)

1

EXPERIMENTAL

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

2

PLACEBO COMPARATOR

Same shape placebo

Drug: Placebo

Interventions

Paroxetine CR DRUG

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.

Also known as: Paxil

1

Placebo DRUG

Placebo

2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Each patient must satisfy all the following criteria before entry into the study:
• Patients must have given their written informed consent to enter the study (after verification of the diagnosis criteria).
• 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).
• 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

You may not qualify if:

• A patient will be excluded from the study if any one of the following criteria applies to that patient:
• 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)
• 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.
• Patients with clinically significant abnormal blood test results at entry to the study, in the opinion of the investigator.
• 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.
• Patients with a history of lactose intolerance prior to the screening.
• Patients with any history of drug or alcohol abuse in the past 6 months.
• Patients on antidepressants for the treatment of mood or anxiety disorders.

Sponsors & Collaborators

• Duke University: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Department of Psychiatry Clinical Trial Team, Duke University

Durham, North Carolina, 27705, United States

Location

Related Publications (1)

• Marks DM, Han C, Krulewicz S, Pae CU, Peindl K, Patkar AA, Masand PS. History of depressive and anxiety disorders and paroxetine response in patients with irritable bowel syndrome: post hoc analysis from a placebo-controlled study. Prim Care Companion J Clin Psychiatry. 2008;10(5):368-75. doi: 10.4088/pcc.v10n0504.

  PMID: 19158975 DERIVED

MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

Paroxetine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Greg Clary, M.D.

  Duke University

  PRINCIPAL INVESTIGATOR

• Ashwin A Patkar, M.D.

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 28, 2008
• First Posted: February 8, 2008
• Study Start: January 1, 2002
• Primary Completion: December 1, 2002
• Study Completion: December 1, 2002
• Last Updated: June 20, 2013

Record last verified: 2008-01

Locations

US (1)