{"protocolSection":{"identificationModule":{"nctId":"NCT01108731","orgStudyIdInfo":{"id":"BIMC #212-09"},"organization":{"fullName":"Beth Israel Medical Center","class":"OTHER"},"briefTitle":"The Effect of Milnacipran in Patients With Fibromyalgia","officialTitle":"The Effect of Milnacipran or Placebo on Ventricular Lactate Levels and Fibromyalgia Induced \"Brain Fog.\""},"statusModule":{"statusVerifiedDate":"2014-10","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2010-03"},"primaryCompletionDateStruct":{"date":"2014-01","type":"ACTUAL"},"completionDateStruct":{"date":"2014-01","type":"ACTUAL"},"studyFirstSubmitDate":"2010-03-30","studyFirstSubmitQcDate":"2010-04-21","studyFirstPostDateStruct":{"date":"2010-04-22","type":"ESTIMATED"},"resultsFirstSubmitDate":"2014-07-07","resultsFirstSubmitQcDate":"2014-10-13","resultsFirstPostDateStruct":{"date":"2014-10-15","type":"ESTIMATED"},"lastUpdateSubmitDate":"2016-05-31","lastUpdatePostDateStruct":{"date":"2016-06-30","type":"ESTIMATED"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"Beth Israel Medical Center","class":"OTHER"}},"oversightModule":{"oversightHasDmc":false},"descriptionModule":{"briefSummary":"Use of the drug Milnacipran will reduce ventricular lactate levels and processing time for completing complex tasks relative to placebo.","detailedDescription":"Patients with Fibromyalgia will show elevated ventricular lactate levels as measured via magnetic resonance spectroscopy (MRS). Patients treated with Milnacipran will show normalization of ventricular lactate levels compared to those treated with placebo, and will also show normalization of the increased latency to respond to complex reaction time probes compared to those treated with placebo."},"conditionsModule":{"conditions":["Fibromyalgia"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE2","PHASE3"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"QUADRUPLE","whoMasked":["PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":37,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Patients taking the drug Milnacipran","type":"ACTIVE_COMPARATOR","description":"Randomize patients signing informed consent and give 50% of them Milnacipran -- blinded to the investigators.","interventionNames":["Drug: Milnacipran"]},{"label":"Patients taking the placebo","type":"PLACEBO_COMPARATOR","description":"Randomize patients signing informed consent and give 50% of them the placebo -- blinded to the investigators.","interventionNames":["Drug: Placebo"]}],"interventions":[{"type":"DRUG","name":"Milnacipran","description":"Patients will take an increasing number of 12.5mg pills for the first 9 days during the \"ramp up\" period and then take one 50mg pill in the morning and one 50mg pill in the evening for the remaining 8 weeks of the study.","armGroupLabels":["Patients taking the drug Milnacipran"],"otherNames":["Savella"]},{"type":"DRUG","name":"Placebo","description":"Patients will take an increasing number of placebo pills for the first 9 days during the \"ramp up\" period and then take one pill in the morning and one in the evening for the remaining 8 weeks of the study.","armGroupLabels":["Patients taking the placebo"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Change in Ventricular Lactate Levels in the Brain","description":"Ventricular lactate levels will be assessed before and at the end of the trial using a scanning method known as magnetic resonance spectroscopy (MRS), which is used to determine the presence and quantity of a number of chemicals in the brain.","timeFrame":"Baseline and 2 months"}],"secondaryOutcomes":[{"measure":"Change in Cognitive Function Assessed by the no Cue Condition of the Attention Network Test (ANT).","description":"The Attention Network Test (ANT) is a computerized test designed to evaluate the efficiency of the attention network. The ANT consists of a set of cued reaction time tasks to assess vigilance and efficiency to detect novel visual stimuli. The ANT also includes a set of flanker tasks during which a decision needs to be made about whether the orientation of a central stimulus is congruent or incongruent with a set of flanking arrows. Scores on the cued reaction time tasks (no cue, centre cue, double cue) reflect latency to respond measured in milliseconds (slower performance equals greater values). The score on the flanker task reflecting executive attention is derived by subtracting obtained latencies on the congruent flanker from the incongruent condition. Based on our prior work, we are hypothesizing that drug treated Ss will show improved performance on the no cue reaction time condition and on the derived executive attention variable compared to placebo treated.","timeFrame":"Baseline and 2 months"},{"measure":"Change in Widespread Pain","description":"Pain was assessed using a visual analog scale (VAS) ranging from 0 (no pain) to 10 (worst pain ever). The baseline value recorded was widespread pain at the time of assessment and the 2 months follow value recorded was widespread pain over the week prior to assessment.","timeFrame":"2 months"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Female or male subjects who fulfill the American College of Rheumatology's case definition for Fibromyalgia.\n* 18 through 68 years of age\n\nExclusion Criteria:\n\n* Pregnant or trying to become pregnant\n* Taking any other Serotonin Norepinephrine Reuptake Inhibitor (SNRI) or already taking milnacipran\n* Patients who do not indicate their pain levels as less than substantial despite their best care\n* History of any psychotic disorder or history of alcoholism or drug abuse within 10 years of intake as determined by psychiatric diagnostic interview\n* Presence of current depression as determined by psychiatric diagnostic interview\n* Presence of brain lesion on MRI anatomical study","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","maximumAge":"68 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Benjamin H Natelson, MD","affiliation":"Beth Israel Medical Center","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"Pain and Fatigue Study Center - Beth Israel Medical Center","city":"New York","state":"New York","zip":"10003","country":"United States","geoPoint":{"lat":40.71427,"lon":-74.00597}}]},"referencesModule":{"references":[{"pmid":"26335989","type":"DERIVED","citation":"Natelson BH, Vu D, Mao X, Weiduschat N, Togo F, Lange G, Blate M, Kang G, Coplan JD, Shungu DC. Effect of Milnacipran Treatment on Ventricular Lactate in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Trial. J Pain. 2015 Nov;16(11):1211-9. doi: 10.1016/j.jpain.2015.08.004. Epub 2015 Aug 31."}],"seeAlsoLinks":[{"label":"The Pain and Fatigue Study Center","url":"http://www.painandfatigue.com"}]},"ipdSharingStatementModule":{"ipdSharing":"NO"}},"resultsSection":{"participantFlowModule":{"preAssignmentDetails":"We got informed consent from 37 patients but excluded 3 -- 2 for saving psychiatric diagnoses that were exclusionary and one for having a metal implant which was an exclusion for neuroimaging. Thus 34 patients were randomized for the trial.","groups":[{"id":"FG000","title":"Patients Taking the Drug Minalcipran","description":"Milnacipran: Patients will take an increasing number of 12.5mg pills for the first 9 days during the \"ramp up\" period and then take one 50mg pill in the morning and one 50mg pill in the evening for the remaining 8 weeks of the study."},{"id":"FG001","title":"Patients Taking the Placebo","description":"Placebo: Patients will take an increasing number of placebo pills for the first 9 days during the \"ramp up\" period and then take one pill in the morning and one in the evening for the remaining 8 weeks of the study."}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"17"},{"groupId":"FG001","numSubjects":"17"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"13"},{"groupId":"FG001","numSubjects":"13"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"4"},{"groupId":"FG001","numSubjects":"4"}]}],"dropWithdraws":[{"type":"Withdrawal by Subject","reasons":[{"groupId":"FG000","numSubjects":"1"},{"groupId":"FG001","numSubjects":"1"}]},{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"3"},{"groupId":"FG001","numSubjects":"3"}]}]}]},"baselineCharacteristicsModule":{"populationDescription":"Had to report widespread pain and to have at least 11 of 18 tender points \\[rated on a 0 to 10 pain intensity scale at 2 or higher\\].","groups":[{"id":"BG000","title":"Patients Taking the Drug Minalcipran","description":"Milnacipran: Patients will take an increasing number of 12.5mg pills for the first 9 days during the \"ramp up\" period and then take one 50mg pill in the morning and one 50mg pill in the evening for the remaining 8 weeks of the study."},{"id":"BG001","title":"Patients Taking the Placebo","description":"Placebo: Patients will take an increasing number of placebo pills for the first 9 days during the \"ramp up\" period and then take one pill in the morning and one in the evening for the remaining 8 weeks of the study."},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"13"},{"groupId":"BG001","value":"13"},{"groupId":"BG002","value":"26"}]}],"measures":[{"title":"Age, Continuous","description":"Age on intake, continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"48","spread":"4"},{"groupId":"BG001","value":"47","spread":"5"},{"groupId":"BG002","value":"47","spread":"4"}]}]}]},{"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":"13"},{"groupId":"BG001","value":"13"},{"groupId":"BG002","value":"26"}]},{"title":">=65 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"13"},{"groupId":"BG001","value":"13"},{"groupId":"BG002","value":"26"}]},{"title":"Male","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":"13"},{"groupId":"BG001","value":"13"},{"groupId":"BG002","value":"26"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Change in Ventricular Lactate Levels in the Brain","description":"Ventricular lactate levels will be assessed before and at the end of the trial using a scanning method known as magnetic resonance spectroscopy (MRS), which is used to determine the presence and quantity of a number of chemicals in the brain.","populationDescription":"One drug treated and two placebo treated could not be analyzed due to excessive head motion","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"international units (iu)","timeFrame":"Baseline and 2 months","groups":[{"id":"OG000","title":"Patients Taking the Drug Minalcipran","description":"Milnacipran: Patients will take an increasing number of 12.5mg pills for the first 9 days during the \"ramp up\" period and then take one 50mg pill in the morning and one 50mg pill in the evening for the remaining 8 weeks of the study."},{"id":"OG001","title":"Patients Taking the Placebo","description":"Placebo: Patients will take an increasing number of placebo pills for the first 9 days during the \"ramp up\" period and then take one pill in the morning and one in the evening for the remaining 8 weeks of the study."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"12"},{"groupId":"OG001","value":"11"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-0.87","spread":"0.91"},{"groupId":"OG001","value":"0.32","spread":"1.58"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"testedNonInferiority":false,"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"<0.05","statisticalMethod":"General Linear Model (GLM)","ciNumSides":"TWO_SIDED"}]},{"type":"SECONDARY","title":"Change in Cognitive Function Assessed by the no Cue Condition of the Attention Network Test (ANT).","description":"The Attention Network Test (ANT) is a computerized test designed to evaluate the efficiency of the attention network. The ANT consists of a set of cued reaction time tasks to assess vigilance and efficiency to detect novel visual stimuli. The ANT also includes a set of flanker tasks during which a decision needs to be made about whether the orientation of a central stimulus is congruent or incongruent with a set of flanking arrows. Scores on the cued reaction time tasks (no cue, centre cue, double cue) reflect latency to respond measured in milliseconds (slower performance equals greater values). The score on the flanker task reflecting executive attention is derived by subtracting obtained latencies on the congruent flanker from the incongruent condition. Based on our prior work, we are hypothesizing that drug treated Ss will show improved performance on the no cue reaction time condition and on the derived executive attention variable compared to placebo treated.","populationDescription":"Data from 4 were excluded due to 2 having error rates greater than 50%, indicating that they did not understand the task and 2 having simple reaction times longer than those for the complex reaction times on the ANT, suggesting their need for additional practice trials on the simple motor reaction time task.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"latency to respond (msecs.)","timeFrame":"Baseline and 2 months","groups":[{"id":"OG000","title":"Patients Taking the Drug Minalcipran","description":"Milnacipran: Patients will take an increasing number of 12.5mg pills for the first 9 days during the \"ramp up\" period and then take one 50mg pill in the morning and one 50mg pill in the evening for the remaining 8 weeks of the study."},{"id":"OG001","title":"Patients Taking the Placebo","description":"Placebo: Patients will take an increasing number of placebo pills for the first 9 days during the \"ramp up\" period and then take one pill in the morning and one in the evening for the remaining 8 weeks of the study."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"11"},{"groupId":"OG001","value":"11"}]}],"classes":[{"title":"No cue condition","categories":[{"measurements":[{"groupId":"OG000","value":"-79.56","spread":"80.45"},{"groupId":"OG001","value":"-35.00","spread":"90.09"}]}]},{"title":"Executive attention","categories":[{"measurements":[{"groupId":"OG000","value":"-68.73","spread":"52.77"},{"groupId":"OG001","value":"-34.77","spread":"52.77"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"testedNonInferiority":false,"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"<0.05","statisticalMethod":"General Linear Model (GLM)","ciNumSides":"TWO_SIDED"}]},{"type":"SECONDARY","title":"Change in Widespread Pain","description":"Pain was assessed using a visual analog scale (VAS) ranging from 0 (no pain) to 10 (worst pain ever). The baseline value recorded was widespread pain at the time of assessment and the 2 months follow value recorded was widespread pain over the week prior to assessment.","populationDescription":"Data from all 26 participants were used for analysis.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"units on a scale","timeFrame":"2 months","groups":[{"id":"OG000","title":"Patients Taking the Drug Minalcipran","description":"Milnacipran: Patients will take an increasing number of 12.5mg pills for the first 9 days during the \"ramp up\" period and then take one 50mg pill in the morning and one 50mg pill in the evening for the remaining 8 weeks of the study."},{"id":"OG001","title":"Patients Taking the Placebo","description":"Placebo: Patients will take an increasing number of placebo pills for the first 9 days during the \"ramp up\" period and then take one pill in the morning and one in the evening for the remaining 8 weeks of the study."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"13"},{"groupId":"OG001","value":"13"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-1.24","spread":"1.57"},{"groupId":"OG001","value":"0.66","spread":"1.75"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"testedNonInferiority":false,"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"<0.05","statisticalMethod":"Wilcoxon (Mann-Whitney)","ciNumSides":"TWO_SIDED"}]}]},"adverseEventsModule":{"frequencyThreshold":"5","timeFrame":"During the 2 month trial","eventGroups":[{"id":"EG000","title":"Patients Taking the Drug Minalcipran","description":"Milnacipran: Patients will take an increasing number of 12.5mg pills for the first 9 days during the \"ramp up\" period and then take one 50mg pill in the morning and one 50mg pill in the evening for the remaining 8 weeks of the study.","seriousNumAffected":0,"seriousNumAtRisk":17,"otherNumAffected":2,"otherNumAtRisk":17},{"id":"EG001","title":"Patients Taking the Placebo","description":"Placebo: Patients will take an increasing number of placebo pills for the first 9 days during the \"ramp up\" period and then take one pill in the morning and one in the evening for the remaining 8 weeks of the study.","seriousNumAffected":0,"seriousNumAtRisk":17,"otherNumAffected":1,"otherNumAtRisk":17}],"otherEvents":[{"term":"Gastric distress, nausea or vomiting","organSystem":"Gastrointestinal disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","notes":"A continuum of gastric distress, to nausea or frank vomiting","stats":[{"groupId":"EG000","numAffected":2,"numAtRisk":17},{"groupId":"EG001","numAffected":1,"numAtRisk":17}]}]},"moreInfoModule":{"certainAgreement":{"piSponsorEmployee":true},"pointOfContact":{"title":"Dr Benjamin Natelson","organization":"Beth_IsraelMC","email":"bnatelson@chpnet.org","phone":"212-844-6747"}}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13"},"conditionBrowseModule":{"meshes":[{"id":"D005356","term":"Fibromyalgia"}],"ancestors":[{"id":"D009135","term":"Muscular Diseases"},{"id":"D009140","term":"Musculoskeletal Diseases"},{"id":"D012216","term":"Rheumatic Diseases"},{"id":"D009468","term":"Neuromuscular Diseases"},{"id":"D009422","term":"Nervous System Diseases"}]},"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}