Milnacipran (Savella) in Irritable Bowel Syndrome (IBS)

Spencer Dorn, MD, MPH

Status and phase: Terminated; Phase 2

Conditions: Irritable Bowel Syndrome

Treatments: Drug: Placebo; Drug: Milnacipran

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01471379

11-1105a

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2 patients

Sex: Female

Ages: 18 to 79 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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2 participants in 3 patient groups, including a placebo group

Group A (50mg - 100mg)

Experimental group

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

Treatment:

Drug: Milnacipran

Drug: Milnacipran

Drug: Milnacipran

Group B (50mg x12)

Active Comparator group

Description:

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

Treatment:

Drug: Milnacipran

Drug: Milnacipran

Drug: Milnacipran

Group C (Placebo - 50mg)

Placebo Comparator group

Description:

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

Treatment:

Drug: Milnacipran

Drug: Milnacipran

Drug: Placebo

Drug: Milnacipran