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Milnacipran (Savella) in Irritable Bowel Syndrome (IBS)

Primary Purpose

Irritable Bowel Syndrome

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Milnacipran
Milnacipran
Milnacipran
Placebo
Sponsored by
Spencer Dorn, MD, MPH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Irritable Bowel Syndrome focused on measuring Irritable Bowel Syndrome, IBS, Savella, Milnacipran, Abdominal Pain

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • UNC Center for Functional GI and Motility Disorders

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Group A (50mg - 100mg)

Group B (50mg x12)

Group C (Placebo - 50mg)

Arm Description

Group A will begin treatment with Milnacipran 50mg BID (n=20) during Phase I and will be increased to 100mg BID during Phase II

Subjects in this arm will be maintained at Milnacipran 50mg BID for the entirety of the 12 weeks of the study.

Group C will begin treatment with Placebo BID (n=20) during Phase I and will be given 50mg BID during Phase II

Outcomes

Primary Outcome Measures

Number of Participants With Pain Response
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 the 12th week; however, subject was terminated at the 10th week visit. A positive pain response (ie pain relief) was defined as >30% decrease in the VAS score between baseline and the final study visit.

Secondary Outcome Measures

Quality of Life ( IBS-QOL)
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
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)
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
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

Full Information

First Posted
November 10, 2011
Last Updated
March 15, 2017
Sponsor
Spencer Dorn, MD, MPH
Collaborators
Forest Laboratories
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1. Study Identification

Unique Protocol Identification Number
NCT01471379
Brief Title
Milnacipran (Savella) in Irritable Bowel Syndrome (IBS)
Official Title
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy of Milnacipran in the Treatment of Irritable Bowel Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Why Stopped
Due to recruitment difficulties the study is terminated.
Study Start Date
April 2012 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
February 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Spencer Dorn, MD, MPH
Collaborators
Forest Laboratories

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Irritable Bowel Syndrome
Keywords
Irritable Bowel Syndrome, IBS, Savella, Milnacipran, Abdominal Pain

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A (50mg - 100mg)
Arm Type
Experimental
Arm Description
Group A will begin treatment with Milnacipran 50mg BID (n=20) during Phase I and will be increased to 100mg BID during Phase II
Arm Title
Group B (50mg x12)
Arm Type
Active Comparator
Arm Description
Subjects in this arm will be maintained at Milnacipran 50mg BID for the entirety of the 12 weeks of the study.
Arm Title
Group C (Placebo - 50mg)
Arm Type
Placebo Comparator
Arm Description
Group C will begin treatment with Placebo BID (n=20) during Phase I and will be given 50mg BID during Phase II
Intervention Type
Drug
Intervention Name(s)
Milnacipran
Other Intervention Name(s)
Savella
Intervention Description
50mg Milnacipran PO, BID, for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Milnacipran
Other Intervention Name(s)
Savella
Intervention Description
Milnacipran, 100mg PO, BID, for six weeks
Intervention Type
Drug
Intervention Name(s)
Milnacipran
Other Intervention Name(s)
Savella
Intervention Description
Milnacipran, 50mg PO BID for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Inactive pill, identical in shape, size, and appearance to active drug, PO, BID.
Primary Outcome Measure Information:
Title
Number of Participants With Pain Response
Description
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 the 12th week; however, subject was terminated at the 10th week visit. A positive pain response (ie pain relief) was defined as >30% decrease in the VAS score between baseline and the final study visit.
Time Frame
Twelve Weeks
Secondary Outcome Measure Information:
Title
Quality of Life ( IBS-QOL)
Description
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.
Time Frame
Six Weeks
Title
Subject Self Reported Adequate Relief of Pain
Description
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.
Time Frame
Twelve Weeks
Title
Treatment Efficacy Questionnaire (TEQ)
Description
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.
Time Frame
Twelve Weeks
Title
Dose Related Incremental Benefit in Pain Reduction Based on VAS
Description
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
Time Frame
12 Weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Spencer D Dorn, MD, MPH
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
UNC Center for Functional GI and Motility Disorders
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States

12. IPD Sharing Statement

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Milnacipran (Savella) in Irritable Bowel Syndrome (IBS)

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