{"protocolSection":{"identificationModule":{"nctId":"NCT01846182","orgStudyIdInfo":{"id":"SPLD-016-12F"},"secondaryIdInfos":[{"id":"6125","type":"OTHER","domain":"Clinical Science Research & Development"}],"organization":{"fullName":"VA Office of Research and Development","class":"FED"},"briefTitle":"Research Examining Gulf War Illness in Our Nations Service Members","officialTitle":"RCT of Duloxetine & Pregabalin for the Treatment of Gulf War Illness in Veterans","acronym":"REGIONS"},"statusModule":{"statusVerifiedDate":"2021-02","overallStatus":"TERMINATED","whyStopped":"Terminated by Funder","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2015-06-24","type":"ACTUAL"},"primaryCompletionDateStruct":{"date":"2019-08-01","type":"ACTUAL"},"completionDateStruct":{"date":"2019-08-01","type":"ACTUAL"},"studyFirstSubmitDate":"2013-04-16","studyFirstSubmitQcDate":"2013-04-30","studyFirstPostDateStruct":{"date":"2013-05-03","type":"ESTIMATED"},"resultsFirstSubmitDate":"2021-02-18","resultsFirstSubmitQcDate":"2021-02-18","resultsFirstPostDateStruct":{"date":"2021-03-12","type":"ACTUAL"},"lastUpdateSubmitDate":"2021-02-18","lastUpdatePostDateStruct":{"date":"2021-03-12","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"VA Office of Research and Development","class":"FED"},"collaborators":[{"name":"Texas A&M University","class":"OTHER"}]},"oversightModule":{"oversightHasDmc":true,"isFdaRegulatedDrug":true,"isFdaRegulatedDevice":false,"isUsExport":false},"descriptionModule":{"briefSummary":"At least 1 in 4 of the 700,000 U.S. Veterans who served in the 1990-1991 Gulf War suffer from Gulf War Illness (GWI). Despite considerable research, effective treatments remain elusive. GWI refers to a complex of symptoms that typically include widespread chronic pain, persistent headache, memory and concentration problems, gastrointestinal difficulties, sleep disturbances and unexplained fatigue. These symptoms are similar to that of fibromyalgia syndrome (FMS), another multi-symptom condition. Whereas, effective treatments for GWI have yet to be found, the FDA has approved duloxetine and pregabalin for the treatment of FMS. The lack of progress in finding effective treatments for GWI, and the similarities between GWI and FMS, provides a rationale for determining if these medications can provide relief to Veterans who suffer from GWI. This randomized controlled trial will test the efficacy of Duloxetine and Pregabalin for treating Gulf War Veterans who suffer from GWI.","detailedDescription":"At least 1 in 4 of the 700,000 U.S. Veterans who served in the 1990-1991 Gulf War suffer from Gulf War Illness (GWI). Despite considerable research, effective treatments remain elusive. GWI refers to a complex of symptoms that typically include widespread chronic pain, persistent headache, memory and concentration problems, gastrointestinal difficulties, sleep disturbances and unexplained fatigue. This symptom profile is similar to that of fibromyalgia syndrome (FMS), a multi-symptom condition similar to GWI. Whereas, effective treatments for GWI have yet to be found, progress has been made in identifying medications to treat FMS. For example, the FDA has approved a number of medications including Duloxetine and Pregabalin for the treatment of FMS. Compared to placebo (PBO) Duloxetine (a serotonin norepinephrine reuptake inhibitor) and Pregabalin (an alpha-2-alpha-subunit calcium-channel ligand) significantly improved pain responses and fatigue. The capacity of Duloxetine to increase central levels of serotonin and norepinephrine as well as the more complex alterations of neurotransmitters and central nervous system (CNS) mediators of pain attributed to pregabalin are thought to be responsible for the medication's effects on pain, mood and sleep. Clinical practice and one open-label trial support the use of these medications in combination to achieve optimal symptom improvement amongst GWI sufferers; however, such combinations have not been formally tested in randomized controlled trials. The lack of progress in finding effective treatments for GWI, and the similarities between GWI and FMS, provides a rationale for determining if these FDA approved medications can provide significant symptomatic relief to Veterans who suffer from GWI. Central Texas is home to one of the highest number of Gulf War Veterans in the nation, thus the investigators' research team is ideally situated to conduct the proposed study. In a randomized, double-blind, controlled trial, 180 Veterans who meet defining criteria for GWI and whose symptom profile includes chronic widespread pain and sleep disturbances will be treated with one of the following medications; 1) AM Duloxetine+ PM placebo (PBO); 2) PM Pregabalin + AM PBO or 3) AM PBO + PM PBO. All active treatments will titrate from a lower dose in 2-week increments to the full therapeutic doses (FDA-approved for FMS). The outcome of the PBO double-dummy period will be compared statistically with 18 weeks of active therapy (weeks 5-22)."},"conditionsModule":{"conditions":["Gulf War Illness"],"keywords":["Gulf War Illness","Pregabalin","Duloxetine","Gulf War Veterans","Cymbalta","Lyrica"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE2"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","interventionModelDescription":"Three arms comparing placebo to duloxetine and pregabalin","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"QUADRUPLE","whoMasked":["PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":112,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Group 1","type":"ACTIVE_COMPARATOR","description":"60 mg of duloxetine in the AM for 20 weeks and placebo in PM","interventionNames":["Drug: Duloxetine","Drug: Placebo"]},{"label":"Group 2","type":"ACTIVE_COMPARATOR","description":"300 mg of pregabalin in the PM for 20 weeks and placebo in AM","interventionNames":["Drug: Pregabalin","Drug: Placebo"]},{"label":"Group 3","type":"PLACEBO_COMPARATOR","description":"placebo in the AM \\& PM for 20 weeks","interventionNames":["Drug: Placebo"]}],"interventions":[{"type":"DRUG","name":"Duloxetine","description":"serotonin norepinephrine reuptake inhibitor","armGroupLabels":["Group 1"],"otherNames":["Cymbalta"]},{"type":"DRUG","name":"Pregabalin","description":"alpha-2-alpha subunit calcium channel ligand","armGroupLabels":["Group 2"],"otherNames":["Lyrica"]},{"type":"DRUG","name":"Placebo","description":"Placebo","armGroupLabels":["Group 1","Group 2","Group 3"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Pain by Likert Scale","description":"Likert scale of pain rating","timeFrame":"120 days"}],"secondaryOutcomes":[{"measure":"Side Effects","description":"Side effects checklist","timeFrame":"Assessed every 2 weeks"}],"otherOutcomes":[{"measure":"Multiple and Unreliable","description":"Reliability of measurement is highly suspect and data are not suitable for analysis.","timeFrame":"Assessed every 2 weeks up to 34 weeks"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Living in Central Texas near Killeen, Austin, Temple or Waco\n* Served on active military duty and deployed to the Persian Gulf region for some period between August 1990 \\& July 1991\n* English speaking and able to understand the consent form and study questionnaires\n* Willing to be randomized to treatment and participate in 1-month follow up\n* men \\& women between the ages of 43 to 70\n* meet Kansas GWI case definition for the diagnosis of GWI\n* report a baseline score \\> 4 on a 10-point Pain Visual Analog Scale (VAS)\n* female participants of childbearing potential must test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a reliable method of birth control (for example, oral contraceptives or Norplant; a reliable barrier method of birth control \\[diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam); intrauterine devices; partner with vasectomy; or abstinence) during the study and for 2 months following the last dose of the study drug. \\[Note that this inclusion criterion applies only to females of childbearing potential. Females of childbearing potential are defined as women not surgically sterilized and between menarche and 2 years post-menopause.\\]\n\nExclusion Criteria:\n\n* Unstable or poorly controlled chronic medical illness such as Diabetes type-II, Hypertension (HTN), heart disease, endocrine disorders, narrow angle glaucoma\n* Significant Central Nervous System disease including transient ischemic attacks (TIAs) or stroke, Dementia, syncopal episodes, severe head trauma, multiple sclerosis\n* Serious or advanced heart disease or clinically relevant abnormal electrocardiogram (ECG), postural hypotension\n* Untreated sleep apnea or body mass index placing patients at risk for undiagnosed sleep apnea (BMI\\> 35 kg/m2)\n* Diabetes type-I and patients with Diabetes type-II associated with peripheral neuropathy, hepatitis, liver failure/cirrhosis\n* End stage renal disease\n* History of hypersensitivity reaction to pregabalin, duloxetine, venlafaxine; active treatment with duloxetine or pregabalin; History of failure of duloxetine or pregabalin at therapeutic doses; history of angioedema reaction to pregabalin\n* Active systemic infectious disease such as tuberculosis and HIV, shingles\n* Autoimmune mediated illnesses such as systemic lupus erythematosis, rheumatoid arthritis, scleroderma\n* History of mental illness requiring hospitalization (depression, bipolar illness, post traumatic stress disorder, history of suicide attempts, psychosis, schizophrenia spectrum); Current major depression of dysthymia; patients lacking capacity to make medical decisions\n* Use of monoamine oxidase inhibitors (MAOIs) within 2 weeks of evaluation; Active ongoing use of the following agents: desvenlafaxine, fenfluramine, linezolid, milnacipran, phentermine, tryptophan, tramadol, opiates\n* Current (meets criterion within the last 6 months) for drug or alcohol dependence (except for nicotine and caffeine)\n* Cancer other than non-melanoma skin cancers\n* Women who are pregnant or desire to become pregnant, breastfeeding, who use unreliable contraception methods\n* Those with occupations requiring use and/or operation of hazardous heavy equipment or professional drivers\n* Patients for whom the potential risk outweighs the potential benefit in the opinion of the treating psychiatrist","healthyVolunteers":false,"sex":"ALL","minimumAge":"44 Years","maximumAge":"70 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Charles J Foulks, M.D.","affiliation":"Central Texas Veterans Health Care System, Temple, TX","role":"STUDY_CHAIR"}],"locations":[{"facility":"Central Texas Veterans Health Care System, Temple, TX","city":"Temple","state":"Texas","zip":"76504","country":"United States","geoPoint":{"lat":31.09823,"lon":-97.34278}},{"facility":"Central Texas Veterans Health Care System Waco VA Medical Center, Waco, TX","city":"Waco","state":"Texas","zip":"76711","country":"United States","geoPoint":{"lat":31.54933,"lon":-97.14667}}]},"ipdSharingStatementModule":{"ipdSharing":"NO"}},"resultsSection":{"participantFlowModule":{"recruitmentDetails":"Patient recruitment was very difficult.","groups":[{"id":"FG000","title":"Group 1","description":"60 mg of duloxetine in the AM for 20 weeks\n\nDuloxetine: serotonin norepinephrine reuptake inhibitor\n\nPlacebo: Placebo"},{"id":"FG001","title":"Group 2","description":"300 mg of pregabalin in the PM for 20 weeks\n\nPregabalin: alpha-2-alpha subunit calcium channel ligand\n\nPlacebo: Placebo"},{"id":"FG002","title":"Group 3","description":"placebo in the AM \\& PM for 20 weeks\n\nPlacebo: Placebo"}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","comment":"Unclear due to assignment records.","numSubjects":"0"},{"groupId":"FG001","comment":"Unclear due to assignment records.","numSubjects":"0"},{"groupId":"FG002","comment":"Unclear due to assignment records.","numSubjects":"0"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","comment":"The data on completion subjects is corrupted and not reliable for interpretation.","numSubjects":"0"},{"groupId":"FG001","comment":"The data on completion subjects is corrupted and not reliable for interpretation.","numSubjects":"0"},{"groupId":"FG002","comment":"The data on completion subjects is corrupted and not reliable for interpretation.","numSubjects":"0"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"}]}]}]},"baselineCharacteristicsModule":{"populationDescription":"Data collection was inaccurate and data are considered unreliable for evaluation.","groups":[{"id":"BG000","title":"Group 1","description":"60 mg of duloxetine in the AM for 20 weeks\n\nDuloxetine: serotonin norepinephrine reuptake inhibitor\n\nPlacebo: Placebo"},{"id":"BG001","title":"Group 2","description":"300 mg of pregabalin in the PM for 20 weeks\n\nPregabalin: alpha-2-alpha subunit calcium channel ligand\n\nPlacebo: Placebo"},{"id":"BG002","title":"Group 3","description":"placebo in the AM \\& PM for 20 weeks\n\nPlacebo: Placebo"},{"id":"BG003","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]}],"measures":[{"title":"Age, Categorical","classes":[{"categories":[{"title":"<=18 years"},{"title":"Between 18 and 65 years"},{"title":">=65 years"}]}]},{"title":"Sex: Female, Male","classes":[{"categories":[{"title":"Female"},{"title":"Male"}]}]},{"title":"Race (NIH/OMB)","classes":[{"categories":[{"title":"American Indian or Alaska Native"},{"title":"Asian"},{"title":"Native Hawaiian or Other Pacific Islander"},{"title":"Black or African American"},{"title":"White"},{"title":"More than one race"},{"title":"Unknown or Not Reported"}]}]},{"title":"Region of Enrollment","unitOfMeasure":"participants","classes":[{"title":"United States"}]},{"title":"Pain"}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Pain by Likert Scale","description":"Likert scale of pain rating","populationDescription":"Data collection was inaccurate and data are considered unreliable for evaluation.","reportingStatus":"POSTED","timeFrame":"120 days","groups":[{"id":"OG000","title":"Group 1","description":"60 mg of duloxetine in the AM for 20 weeks and placebo in PM\n\nDuloxetine: serotonin norepinephrine reuptake inhibitor\n\nPlacebo: Placebo"},{"id":"OG001","title":"Group 2","description":"300 mg of pregabalin in the PM for 20 weeks and placebo in AM\n\nPregabalin: alpha-2-alpha subunit calcium channel ligand\n\nPlacebo: Placebo"},{"id":"OG002","title":"Group 3","description":"placebo in the AM \\& PM for 20 weeks\n\nPlacebo: Placebo"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"}]}]},{"type":"SECONDARY","title":"Side Effects","description":"Side effects checklist","populationDescription":"Data collection was inaccurate and data are considered unreliable for evaluation.","reportingStatus":"POSTED","timeFrame":"Assessed every 2 weeks","groups":[{"id":"OG000","title":"Group 1","description":"60 mg of duloxetine in the AM for 20 weeks\n\nDuloxetine: serotonin norepinephrine reuptake inhibitor\n\nPlacebo: Placebo"},{"id":"OG001","title":"Group 2","description":"300 mg of pregabalin in the PM for 20 weeks\n\nPregabalin: alpha-2-alpha subunit calcium channel ligand\n\nPlacebo: Placebo"},{"id":"OG002","title":"Group 3","description":"placebo in the AM \\& PM for 20 weeks\n\nPlacebo: Placebo"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"}]}]},{"type":"OTHER_PRE_SPECIFIED","title":"Multiple and Unreliable","description":"Reliability of measurement is highly suspect and data are not suitable for analysis.","populationDescription":"Data were inaccurately collected and are considered unreliable for interpretation.","reportingStatus":"POSTED","timeFrame":"Assessed every 2 weeks up to 34 weeks","groups":[{"id":"OG000","title":"Group 1","description":"60 mg of duloxetine in the AM for 20 weeks\n\nDuloxetine: serotonin norepinephrine reuptake inhibitor\n\nPlacebo: Placebo"},{"id":"OG001","title":"Group 2","description":"300 mg of pregabalin in the PM for 20 weeks\n\nPregabalin: alpha-2-alpha subunit calcium channel ligand\n\nPlacebo: Placebo"},{"id":"OG002","title":"Group 3","description":"placebo in the AM \\& PM for 20 weeks\n\nPlacebo: Placebo"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"}]}]}]},"adverseEventsModule":{"frequencyThreshold":"0","timeFrame":"Entire study data are unreliable.","description":"Event collection appears to be inadequate and data are considered to be unreliable.","eventGroups":[{"id":"EG000","title":"Group 1","description":"60 mg of duloxetine in the AM for 20 weeks\n\nDuloxetine: serotonin norepinephrine reuptake inhibitor\n\nPlacebo: Placebo","deathsNumAffected":0,"deathsNumAtRisk":0,"seriousNumAffected":0,"seriousNumAtRisk":0,"otherNumAffected":0,"otherNumAtRisk":0},{"id":"EG001","title":"Group 2","description":"300 mg of pregabalin in the PM for 20 weeks\n\nPregabalin: alpha-2-alpha subunit calcium channel ligand\n\nPlacebo: Placebo","deathsNumAffected":0,"deathsNumAtRisk":0,"seriousNumAffected":0,"seriousNumAtRisk":0,"otherNumAffected":0,"otherNumAtRisk":0},{"id":"EG002","title":"Group 3","description":"placebo in the AM \\& PM for 20 weeks\n\nPlacebo: Placebo","deathsNumAffected":0,"deathsNumAtRisk":0,"seriousNumAffected":0,"seriousNumAtRisk":0,"otherNumAffected":0,"otherNumAtRisk":0}]},"moreInfoModule":{"limitationsAndCaveats":{"description":"The study was closed by the sponsor. Recruiting was very difficult and there were multiple irregularities in enrollment, data collection, and study management. The data are unreliable for interpretation."},"certainAgreement":{"piSponsorEmployee":true},"pointOfContact":{"title":"Charles J. Foulks, M.D., ACOS/R","organization":"Central Texas Veterans Health Care System","email":"Charles.Foulks@va.gov","phone":"254 743 2643"}}},"documentSection":{"largeDocumentModule":{"largeDocs":[{"typeAbbrev":"Prot_SAP","hasProtocol":true,"hasSap":true,"hasIcf":false,"label":"Study Protocol and Statistical Analysis Plan","date":"2019-05-23","uploadDate":"2021-02-18T17:31","filename":"Prot_SAP_000.pdf","size":546526}]}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13"},"interventionBrowseModule":{"meshes":[{"id":"D000068736","term":"Duloxetine Hydrochloride"},{"id":"D000069583","term":"Pregabalin"}],"ancestors":[{"id":"D013876","term":"Thiophenes"},{"id":"D013457","term":"Sulfur Compounds"},{"id":"D009930","term":"Organic Chemicals"},{"id":"D006573","term":"Heterocyclic Compounds, 1-Ring"},{"id":"D006571","term":"Heterocyclic Compounds"},{"id":"D005680","term":"gamma-Aminobutyric Acid"},{"id":"D000613","term":"Aminobutyrates"},{"id":"D002087","term":"Butyrates"},{"id":"D000144","term":"Acids, Acyclic"},{"id":"D002264","term":"Carboxylic Acids"},{"id":"D000596","term":"Amino Acids"},{"id":"D000602","term":"Amino Acids, Peptides, and Proteins"}]}},"hasResults":true}