Milnacipran (Savella) in Irritable Bowel Syndrome (IBS)

This study has been terminated.
(Due to recruitment difficulties the study is terminated.)
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Spencer Dorn, MD, MPH, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01471379
First received: November 10, 2011
Last updated: November 5, 2013
Last verified: November 2013
  Purpose

Purpose: The investigators are proposing to examine the use of Savella® (Milnacipran) for treating irritable bowel syndrome (IBS) in women.

Participants: Eligible participants will meet the Rome III diagnostic criteria for IBS.

Procedures: This study will observe patients treated with Savella® as well as patients treated with a placebo (pill with no active drug). The investigators will monitor and compare several patient and symptom related outcomes, as well as evaluate health related quality of life, psychological distress and related psychosocial measures to determine if the addition of Savella® improves clinical pain response as well as secondary outcomes including quality of life.


Condition Intervention Phase
Irritable Bowel Syndrome
Drug: Milnacipran
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy of Milnacipran in the Treatment of Irritable Bowel Syndrome

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Pain Response [ Time Frame: Twelve Weeks ] [ Designated as safety issue: No ]
    Visual Analog Scale (VAS) scores (range 0-100 mm; 0 = none, 100 = worst pain) were recorded for pain before the beginning of the study, at 6 weeks of treatment and at the end visit i.e. 10 weeks. Ideally, VAS would have been administered at 12th week; however, subject was terminated at 10th week visit. More than >30% relief in pain would have been considered better outcome.


Secondary Outcome Measures:
  • Quality of Life ( IBS-QOL) [ Time Frame: Six Weeks ] [ Designated as safety issue: No ]
    After six weeks of treatment with Milnacipran, treatment groups were compared with placebo for clinically significant improvement in IBS-QOL. 11 point reduction in IBS-QOL compared to baseline was considered as clinically significant improvement.

  • Subject Self Reported Adequate Relief of Pain [ Time Frame: Twelve Weeks ] [ Designated as safety issue: No ]
    The study sought to determine if the Milnacipran arms had a greater proportion of adequate relief over the placebo group. Subjects were asked to answer 'yes' or 'no' as to whether or not they had adequate relief of pain due to irritable bowel syndrome.

  • Treatment Efficacy Questionnaire (TEQ) [ Time Frame: Twelve Weeks ] [ Designated as safety issue: No ]
    Treatment Efficacy Questionnaire is a measure of treatment effectiveness. The score ranges from 1 to 48, 1 is minimum score and 48 is the maximum score. The investigators was looking to see if the Milnacipran treatment groups have a higher proportion of subjects with significant improvement in efficacy, judged as a TEQ score of >28, compared to placebo group.

  • Dose Related Incremental Benefit in Pain Reduction Based on VAS [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    The investigator was looking to see if, for group A, when increased from 50 mg BID to 100 mg BID there is significant improvement of pain scores i.e. 30% pain reduction, and for group C, if there was significant improvement of pain scores when switched from placebo to 50 mg BID of Milnacipran


Enrollment: 2
Study Start Date: April 2012
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A (50mg - 100mg)
Group A will begin treatment with Milnacipran 50mg BID (n=20) during Phase I and will be increased to 100mg BID during Phase II
Drug: Milnacipran
50mg Milnacipran PO, BID, for 6 weeks.
Other Name: Savella
Drug: Milnacipran
Milnacipran, 100mg PO, BID, for six weeks
Other Name: Savella
Active Comparator: Group B (50mg x12)
Subjects in this arm will be maintained at Milnacipran 50mg BID for the entirety of the 12 weeks of the study.
Drug: Milnacipran
Milnacipran, 50mg PO BID for 12 weeks
Other Name: Savella
Placebo Comparator: Group C (Placebo - 50mg)
Group C will begin treatment with Placebo BID (n=20) during Phase I and will be given 50mg BID during Phase II
Drug: Milnacipran
50mg Milnacipran PO, BID, for 6 weeks.
Other Name: Savella
Drug: Placebo
Inactive pill, identical in shape, size, and appearance to active drug, PO, BID.

Detailed Description:

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized primarily by abdominal pain associated with bowel dysfunction. Like many other painful functional somatic syndromes (e.g. fibromyalgia) the pathophysiology of IBS includes abnormal responses to pain and dysregulation of brain-body pain pathways. IBS affects up to 10% of the population, is a leading reason for visits to gastroenterologists and primary care doctors, and, in the United States, annually accrues health care costs over $20 billion.

In their practice the investigators use centrally acting agents to treat IBS. Historically, the investigators have used tricyclic antidepressants based on results of clinical trials, including our NIH funded trial on desipramine. Nonetheless, these agents can produce side effects that limit their full application. More recently the investigators have begun to use SNRIs because they have been shown to benefit for various pain syndromes like diabetic neuropathy, fibromyalgia. The initial impression is that Milnacipran helps improve IBS symptoms and global well being. There is now a need to systematically determine Milnacipran's value for IBS.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meet Rome III criteria for IBS and have no red flags.
  • Must have had a colonoscopy within the previous 5 years to exclude inflammatory or other bowel disease
  • Be fluent and literate in English
  • Must either be of non-childbearing potential or agree to utilize approved birth control for the duration of the study

Exclusion Criteria:

  • Diagnosis or treatment of any clinically symptomatic biochemical or structural abnormality of the GI tract within 6 months prior to screening, or active disease within 6 months prior to screening.
  • Any other diagnosis to explain the abdominal pain,
  • Clinical evidence of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematologic, neurologic, psychiatric or any disease that may interfere with the subject successfully completing the trial
  • Hepatic dysfunction (ALT [SGPT] or AST [SGOT] >3 times the upper limit of normal) or renal impairment (serum creatinine > 2mg/dL)
  • Has disease affecting electrolytes balance, such as SIADH with serum Sodium less than 130mmol/L
  • Any evidence of or treatment of malignancy (other than localized basal cell, squamous cell skin cancer or cancer in situ that has been resected) within the previous year
  • Any surgery on the stomach, small intestine or colon, excluding appendectomy
  • A major psychiatric disorder (DSM-III-R or DSM-IV) including major depression or other psychoses that has required hospitalization in the last 1 year.
  • History of attempted suicide or uncontrolled bipolar disorder.
  • Currently using antidepressants for psychiatric conditions like major depression. Use of TCA or SSRI class antidepressant acceptable if being used specifically for treatment of bowel symptoms and patient is willing to taper off the medication
  • Previous use of Milnacipran or other SNRI antidepressant (duloxetine, venlafaxine, desvenlafaxine)
  • A diagnosis of seizure disorder
  • A diagnosis of glaucoma
  • Currently taking heparin or warfarin
  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: NCT01471379

Locations
United States, North Carolina
UNC Center for Functional GI and Motility Disorders
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
Spencer Dorn, MD, MPH
Forest Laboratories
Investigators
Principal Investigator: Spencer D Dorn, MD, MPH University of North Carolina, Chapel Hill
  More Information

No publications provided

Responsible Party: Spencer Dorn, MD, MPH, Assistant Professor of Medicine, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01471379     History of Changes
Other Study ID Numbers: 11-1105-UNC
Study First Received: November 10, 2011
Results First Received: July 3, 2013
Last Updated: November 5, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
Irritable Bowel Syndrome
IBS
Savella
Milnacipran
Abdominal Pain

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

ClinicalTrials.gov processed this record on August 27, 2014