Savella in Treatment for Provoked Vestibulodynia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01304589
Recruitment Status : Completed
First Posted : February 25, 2011
Results First Posted : April 2, 2014
Last Update Posted : August 18, 2014
Forest Laboratories
Information provided by (Responsible Party):
Candace Brown, MSN, Pharm.D., University of Tennessee

Brief Summary:
The primary aim of this study is to determine the efficacy of milnacipran in reducing pain in women with provoked vestibulodynia (PVD), a centrally mediated pain syndrome similar to fibromyalgia, that is characterized by severe pain in the vestibule (outer vagina). The investigators will also determine whether associated symptoms in PVD, including psychological distress, impairment of sexual function, physical function, and quality of life, are correlated with a reduction in vulvar pain.

Condition or disease Intervention/treatment Phase
Vestibulodynia Vulvodynia Drug: Milnacipran Phase 3

Detailed Description:
This is an 18-week, open-label, flexible-dose "proof of concept" trial where women with a diagnosis of vestibulodynia will be evaluated at baseline for eligibility. Eligible patients will be openly treated with 200 mg/d milnacipran (or the maximum tolerated dose) for a total of 12 weeks. The study design involves 4 phases: screening and washout, baseline assessment, dose escalation, and stable-dose phase (Figure 1). After completing a 2-week washout of prohibited medications, patients will enter a 2-week baseline period, where they will be trained in the use of daily diaries and the tampon test, and baseline safety and efficacy data will be recorded. Patients who continue to meet the eligibility criteria at the end of the baseline period will begin a 6-week period of dose escalation. All patients will be scheduled to receive a total of 12 weeks of stable dose treatment after the 6-week dose-escalation period for a total of 18 weeks of drug exposure.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Trial of Milnacipran in the Treatment of Women With Provoked Vestibulodynia
Study Start Date : October 2010
Actual Primary Completion Date : September 2012
Actual Study Completion Date : September 2012

Arm Intervention/treatment
Experimental: Milnacipran Drug: Milnacipran
6-week titration period starting at 12.5mg daily and moving up to 200mg daily (or maximum tolerated dose)for 12 weeks - total treatment period is 18 weeks
Other Name: Savella

Primary Outcome Measures :
  1. Pain Rating Index [ Time Frame: 18 weeks ]
    The primary outcome measure will be pain ratings on the Pain Rating Index (PRI) of the short-form McGill Pain Questionnaire (SF-MPQ), which consists of 15 representative words from the sensory (n = 11) and affective (N = 4) categories of the standard, long-form (LF-MPQ). On the PRI, each descriptor is ranked by the patient on an intensity scale of 0 = none, 1 = mild, 2 = moderate, 3 = severe. Total score - "0" equals no pain to "45" equals severe pain. The paired t-test was used to compare the PRI score at baseline and at 18 weeks or to further clarify, pre-treatment versus post-treatment comparison.

Secondary Outcome Measures :
  1. Tampon Pain [ Time Frame: 18 weeks ]
    Subjects completed a "tampon insertion pain" test once a week in their daily diary. The values were averaged and compared pre-treatment versus post-treatment.

  2. Coital Pain [ Time Frame: 18 weeks ]
    Intercourse pain is measured by completing a daily diary

  3. 24-hour Vulvar Pain [ Time Frame: 18 weeks ]
    Measures average vulvar pain over 24-hours on daily diary

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Ages Eligible for Study:   18 Years to 54 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. women between 18-54 years of age,
  2. 'Friedrich's Criteria' must be met (report greater than six continuous months of vulvar symptoms including insertional dyspareunia or pain to touch, demonstrate on physical exam moderate to severe tenderness to light touch, localized to the vulvar vestibule [positive Cotton Swab Test] and demonstration of variable degrees of erythema of the vestibule),
  3. an average pain level of "4" or greater on the 10-point tampon test and/or an average pain level of "4" or greater on the sexual intercourse pain scale(0 = no pain at all; 10 = worse pain ever) during the 2-week screening period(see Study Parameters Section), and
  4. willing to use two forms of contraception during the study.

Exclusion Criteria:

  1. other vulvar conditions, including dermatoses, vulvitis, vulvar papillomatosis, and atrophic vaginitis (presence of a maturation index),
  2. previous vestibulectomy,
  3. active vaginal infection,
  4. neuropathology, including seizure disorder or syncopal episodes,
  5. pregnancy or at risk for pregnancy and not using a reliable birth control method for at least 3 months prior to entering the study,
  6. breastfeeding,
  7. major medical illness including chronic liver disease/hepatic impairment, renal impairment, narrow-angle glaucoma, or uncontrolled hypertension,
  8. major psychiatric illness including substance abuse,
  9. multiple allergies (greater than three drugs or environmental agents),
  10. use of centrally-acting agents, including monoamine oxidase inhibitors, benzodiazepines, opiates, muscle relaxants, and antidepressants within 2 weeks of randomization and during the study, and
  11. use of topical lidocaine, within 2 weeks of randomization and during the study, as it has shown to be an effective treatment in some women, while worsening symptoms in others. Subjects will be permitted to take acetaminophen, aspirin, or a nonsteroidal anti-inflammatory drug as rescue medication. They will be provided with a list of allowable escape medications and those which would constitute a protocol deviation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01304589

United States, Tennessee
Women's Health Specialists, PLLC
Germantown, Tennessee, United States, 38138
Sponsors and Collaborators
University of Tennessee
Forest Laboratories
Principal Investigator: Candace S Brown, PharmD University of Tennessee Health Science Center

Responsible Party: Candace Brown, MSN, Pharm.D., Professor, Departments of Clinical Pharmacy, Psychiatry and Obstetrics/Gynecology, University of Tennessee Identifier: NCT01304589     History of Changes
Other Study ID Numbers: CSBrown SAV-MD-18
First Posted: February 25, 2011    Key Record Dates
Results First Posted: April 2, 2014
Last Update Posted: August 18, 2014
Last Verified: August 2014

Keywords provided by Candace Brown, MSN, Pharm.D., University of Tennessee:
provoked vestibulodynia

Additional relevant MeSH terms:
Vulvar Vestibulitis
Vulvar Diseases
Genital Diseases, Female
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Adrenergic Uptake Inhibitors
Adrenergic Agents