{"protocolSection":{"identificationModule":{"nctId":"NCT01288937","orgStudyIdInfo":{"id":"AAAF3404"},"organization":{"fullName":"Columbia University","class":"OTHER"},"briefTitle":"A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain","officialTitle":"A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain"},"statusModule":{"statusVerifiedDate":"2020-08","overallStatus":"TERMINATED","whyStopped":"Poor recruitment","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2011-04-05","type":"ACTUAL"},"primaryCompletionDateStruct":{"date":"2014-10-22","type":"ACTUAL"},"completionDateStruct":{"date":"2014-12-23","type":"ACTUAL"},"studyFirstSubmitDate":"2011-02-01","studyFirstSubmitQcDate":"2011-02-02","studyFirstPostDateStruct":{"date":"2011-02-03","type":"ESTIMATED"},"resultsFirstSubmitDate":"2017-03-14","resultsFirstSubmitQcDate":"2020-08-19","resultsFirstPostDateStruct":{"date":"2020-09-03","type":"ACTUAL"},"lastUpdateSubmitDate":"2020-08-19","lastUpdatePostDateStruct":{"date":"2020-09-03","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"PRINCIPAL_INVESTIGATOR","investigatorFullName":"Thomas Brannagan","investigatorTitle":"Professor of Clinical Neurology","investigatorAffiliation":"Columbia University"},"leadSponsor":{"name":"Columbia University","class":"OTHER"},"collaborators":[{"name":"Forest Laboratories","class":"INDUSTRY"}]},"oversightModule":{"oversightHasDmc":false,"isFdaRegulatedDrug":true,"isFdaRegulatedDevice":false,"isUsExport":false},"descriptionModule":{"briefSummary":"This is an 11-week randomized, double-blind, placebo-controlled trial of Milnacipran 100 mg/d in patients with idiopathic neuropathic pain. Milnacipran, a dual norepinephrine and serotonin reuptake inhibitor has been a safe and beneficial treatment for patients with fibromyalgia and may be useful to treat patients with painful peripheral neuropathy.\n\nThe primary outcome will be assessed by the change in daily averaged weekly 0-10 pain intensity score, from baseline to week 9, by intention to treat analysis. The same analysis will be used on several secondary measures including daily averaged weekly 0-10 pain intensity score the sleep interference scale and the Rand-36 quality of life scale.","detailedDescription":"Milnacipran helps serotonin and noradrenaline work more effectively on the central nervous system. Serotonin and noradrenaline are molecules made by the brain that affect how your body responds to pain. Milnacipran, a dual norepinephrine and serotonin reuptake inhibitor has been a safe and beneficial treatment for patients with fibromyalgia and may be useful to treat patients with painful peripheral neuropathy. Many clinical trials for neuropathy pain are done in patients with diabetic neuropathy. Idiopathic neuropathy however, is a common cause of neuropathy and accounts for 25% of all neuropathies, and over 50% of small fiber neuropathies. The information in this study will provide information on whether milnacipran also provide benefit as a medication for neuropathic pain."},"conditionsModule":{"conditions":["Idiopathic Peripheral Neuropathy"],"keywords":["Milnacipran","Idiopathic Peripheral Neuropathy","Diabetic neuropathy","Neuropathic pain"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE3"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"QUADRUPLE","whoMasked":["PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":6,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Milnacipran","type":"EXPERIMENTAL","description":"Patients will receive Milnacipran","interventionNames":["Drug: Milnacipran"]},{"label":"Placebo","type":"PLACEBO_COMPARATOR","description":"Patients will receive Placebo","interventionNames":["Drug: Placebo"]}],"interventions":[{"type":"DRUG","name":"Milnacipran","description":"Patients will be randomly assigned to receive milnacipran 100 mg/day (including a 1 week dose titration period):\n\nDay 1: 12.5 mg once Day 2, 3: 25 mg/day (12.5 mg twice daily) Day 4, 7: 50 mg/day (25 mg twice daily) After Day 7: 100 mg/day (50 mg twice daily)","armGroupLabels":["Milnacipran"],"otherNames":["Savella"]},{"type":"DRUG","name":"Placebo","description":"Patients will be randomly assigned to placebo for 9 weeks (including a 1 week dose titration period), matching the schedule of the study drug.","armGroupLabels":["Placebo"],"otherNames":["Placebo Pill"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Likert Pain Scale Score","description":"The Likert Pain Scale Score is a psychometric scale commonly involved in research that employs questionnaires to measure the intensity of pain. It is used to determine the level of pain for research participants. The minimum score of 0 indicates \"no pain\" which is the better score and the maximum and total score of 10 indicates the \"the worst possible pain\" which is the worse outcome . Scores 1-3= Mild, scores 4-6= Moderate, scores 7-10= Severe. It is the most widely used approach to scaling responses in survey research. Patients will fill out a pain diary from baseline to end of treatment. This will be used to assess if there was a reduction in pain of the daily averaged weekly 0-10 pain scale at week 9 compared to the baseline. The Unit of Measure is the scores on the scale.","timeFrame":"Baseline, 9 weeks"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Male and female patients age 18 to 80 years\n* Patients with signs and symptoms of a peripheral neuropathy, with either abnormal nerve conductions or abnormal epidermal nerve fiber density with neuropathic pain.\n* Pain will have been present for at least 6 months\n* Patients may be on other medications for neuropathic pain (eg, antiepileptic medications, opiates or non steroidal antiinflammatories); however they must be on a stable dose for 4 weeks prior to, with no plan to change during the study\n* All patients must have had a normal fasting glucose or B12, thyroid stimulating hormone, and serum protein electrophoresis, since the onset of their symptoms.\n\nExclusion Criteria:\n\n* Other cause of neuropathy (eg, diabetic neuropathy, toxic neuropathy, HIV neuropathy, celiac neuropathy, inherited neuropathy)\n* Unstable angina\n* Use of another serotonin and norepinephrine reuptake inhibitors (eg, duloxetine, venlafaxine), tricyclic antidepressants, monoamine oxidase inhibitors (MAOI) or selective serotonin reuptake inhibitors\n* Myocardial infarction stroke or life threatening arrhythmia within the last 6 months\n* HIV infection\n* Hepatic or renal failure\n* Pregnancy\n* narrow angle glaucoma\n* History of epilepsy or a seizure","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","maximumAge":"80 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Thomas H Brannagan III, MD","affiliation":"Columbia University","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"Columbia University Medical Center","city":"New York","state":"New York","zip":"10032","country":"United States","geoPoint":{"lat":40.71427,"lon":-74.00597}}]},"ipdSharingStatementModule":{"ipdSharing":"UNDECIDED"}},"resultsSection":{"participantFlowModule":{"preAssignmentDetails":"Prior to randomization, subjects are assessed at baseline with neurological examinations, physical examination and pain questionnaire/diary.","recruitmentDetails":"Patients will be recruited from the practices of the investigators of the peripheral neuropathy center. These subjects will already be receiving treatment in the clinics and private practices of neurologists at the Neurological Institute.\n\nPatients will also be recruited from physician referrals and advertising.","groups":[{"id":"FG000","title":"Milnacipran","description":"Patients will be randomly assigned to receive milnacipran 100 mg/day (including a 1 week dose titration period):\n\nDay 1: 12.5 mg once Day 2, 3: 25 mg/day (12.5 mg twice daily) Day 4, 7: 50 mg/day (25 mg twice daily) After Day 7: 100 mg/day (50 mg twice daily)"},{"id":"FG001","title":"Placebo","description":"Patients will be randomly assigned to placebo for 9 weeks (including a 1 week dose titration period)."}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"4"},{"groupId":"FG001","numSubjects":"2"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"3"},{"groupId":"FG001","numSubjects":"2"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"1"},{"groupId":"FG001","numSubjects":"0"}]}],"dropWithdraws":[{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"1"},{"groupId":"FG001","numSubjects":"0"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Milnacipran","description":"Patients will be randomly assigned to receive milnacipran 100 mg/day (including a 1 week dose titration period):\n\nDay 1: 12.5 mg once Day 2, 3: 25 mg/day (12.5 mg twice daily) Day 4, 7: 50 mg/day (25 mg twice daily) After Day 7: 100 mg/day (50 mg twice daily)"},{"id":"BG001","title":"Placebo","description":"Patients will be randomly assigned to placebo for 9 weeks (including a 1 week dose titration period)."},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"4"},{"groupId":"BG001","value":"2"},{"groupId":"BG002","value":"6"}]}],"measures":[{"title":"Age, Categorical","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"<=18 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Between 18 and 65 years","measurements":[{"groupId":"BG000","value":"4"},{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"5"}]},{"title":">=65 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"1"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"1"},{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"2"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"3"},{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"4"}]}]}]},{"title":"Race (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"American Indian or Alaska Native","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Asian","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Native Hawaiian or Other Pacific Islander","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Black or African American","measurements":[{"groupId":"BG000","value":"1"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"1"}]},{"title":"White","measurements":[{"groupId":"BG000","value":"3"},{"groupId":"BG001","value":"2"},{"groupId":"BG002","value":"5"}]},{"title":"More than one race","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]}]}]},{"title":"Region of Enrollment","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"United States","categories":[{"measurements":[{"groupId":"BG000","value":"4"},{"groupId":"BG001","value":"2"},{"groupId":"BG002","value":"6"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Likert Pain Scale Score","description":"The Likert Pain Scale Score is a psychometric scale commonly involved in research that employs questionnaires to measure the intensity of pain. It is used to determine the level of pain for research participants. The minimum score of 0 indicates \"no pain\" which is the better score and the maximum and total score of 10 indicates the \"the worst possible pain\" which is the worse outcome . Scores 1-3= Mild, scores 4-6= Moderate, scores 7-10= Severe. It is the most widely used approach to scaling responses in survey research. Patients will fill out a pain diary from baseline to end of treatment. This will be used to assess if there was a reduction in pain of the daily averaged weekly 0-10 pain scale at week 9 compared to the baseline. The Unit of Measure is the scores on the scale.","populationDescription":"For the milnacipran arm, 4 subjects were enrolled; however, 1 subject did not complete the study (due to AE: stomach pain) and was not included in the outcome measure data collection/analysis.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Full Range","unitOfMeasure":"Scores on a scale","timeFrame":"Baseline, 9 weeks","groups":[{"id":"OG000","title":"Milnacipran","description":"Patients will be randomly assigned to receive milnacipran 100 mg/day (including a 1 week dose titration period):\n\nDay 1: 12.5 mg once Day 2, 3: 25 mg/day (12.5 mg twice daily) Day 4, 7: 50 mg/day (25 mg twice daily) After Day 7: 100 mg/day (50 mg twice daily)"},{"id":"OG001","title":"Placebo","description":"Patients will be randomly assigned to placebo for 9 weeks (including a 1 week dose titration period)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"3"},{"groupId":"OG001","value":"2"}]}],"classes":[{"title":"Baseline","categories":[{"measurements":[{"groupId":"OG000","value":"5.6","lowerLimit":"3.1","upperLimit":"8"},{"groupId":"OG001","value":"7.15","lowerLimit":"5.7","upperLimit":"8.6"}]}]},{"title":"9 Weeks","categories":[{"measurements":[{"groupId":"OG000","value":"3.2","lowerLimit":"1.4","upperLimit":"6.6"},{"groupId":"OG001","value":"5.15","lowerLimit":"4.3","upperLimit":"6"}]}]}]}]},"adverseEventsModule":{"frequencyThreshold":"5","timeFrame":"Baseline to 9 weeks.","description":"The definition of adverse event (AE) and/or serious adverse event used to collect AE information is the same as the ClinicalTrials.gov definitions.","eventGroups":[{"id":"EG000","title":"Milnacipran","description":"Patients will be randomly assigned to receive milnacipran 100 mg/day (including a 1 week dose titration period):\n\nDay 1: 12.5 mg once Day 2, 3: 25 mg/day (12.5 mg twice daily) Day 4, 7: 50 mg/day (25 mg twice daily) After Day 7: 100 mg/day (50 mg twice daily)","deathsNumAffected":0,"deathsNumAtRisk":4,"seriousNumAffected":0,"seriousNumAtRisk":4,"otherNumAffected":2,"otherNumAtRisk":4},{"id":"EG001","title":"Placebo","description":"Patients will be randomly assigned to placebo for 9 weeks (including a 1 week dose titration period).","deathsNumAffected":0,"deathsNumAtRisk":2,"seriousNumAffected":0,"seriousNumAtRisk":2,"otherNumAffected":0,"otherNumAtRisk":2}],"otherEvents":[{"term":"Erectile Dysfunction","organSystem":"Reproductive system and breast disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":4},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":2}]},{"term":"Stomach Pain","organSystem":"Gastrointestinal disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":1,"numAtRisk":4},{"groupId":"EG001","numAffected":0,"numAtRisk":2}]}]},"moreInfoModule":{"limitationsAndCaveats":{"description":"Study was terminated and target accrual was unmet due to pre-screening exclusion criteria: 1) excluded concomitant medicines; and 2) patients who had prediabetes."},"certainAgreement":{"piSponsorEmployee":true},"pointOfContact":{"title":"Thomas H. Brannagan, MD","organization":"Columbia University","email":"tb2325@cumc.columbia.edu","phone":"(212) 305-0405"}}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13"},"conditionBrowseModule":{"meshes":[{"id":"D003929","term":"Diabetic Neuropathies"},{"id":"D009437","term":"Neuralgia"}],"ancestors":[{"id":"D010523","term":"Peripheral Nervous System Diseases"},{"id":"D009468","term":"Neuromuscular Diseases"},{"id":"D009422","term":"Nervous System Diseases"},{"id":"D048909","term":"Diabetes Complications"},{"id":"D003920","term":"Diabetes Mellitus"},{"id":"D004700","term":"Endocrine System Diseases"},{"id":"D010146","term":"Pain"},{"id":"D009461","term":"Neurologic Manifestations"},{"id":"D012816","term":"Signs and Symptoms"},{"id":"D013568","term":"Pathological Conditions, Signs and Symptoms"}]},"interventionBrowseModule":{"meshes":[{"id":"D000078764","term":"Milnacipran"}],"ancestors":[{"id":"D003521","term":"Cyclopropanes"},{"id":"D003516","term":"Cycloparaffins"},{"id":"D006840","term":"Hydrocarbons, Alicyclic"},{"id":"D006844","term":"Hydrocarbons, Cyclic"},{"id":"D006838","term":"Hydrocarbons"},{"id":"D009930","term":"Organic Chemicals"}]}},"hasResults":true}