Ignite Creation Date:
2025-12-25 @ 1:17 AM
Ignite Modification Date:
2026-04-25 @ 4:00 PM
Study NCT ID:
NCT02989493
Status:
COMPLETED
Last Update Posted:
2021-03-18
First Post:
2016-12-01
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Testing Doxazosin to Treat Stress Mechanisms in Alcoholism
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2021-03-17', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D000437', 'term': 'Alcoholism'}, {'id': 'D001008', 'term': 'Anxiety Disorders'}, {'id': 'D012008', 'term': 'Recurrence'}], 'ancestors': [{'id': 'D019973', 'term': 'Alcohol-Related Disorders'}, {'id': 'D019966', 'term': 'Substance-Related Disorders'}, {'id': 'D064419', 'term': 'Chemically-Induced Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D017292', 'term': 'Doxazosin'}], 'ancestors': [{'id': 'D011224', 'term': 'Prazosin'}, {'id': 'D011799', 'term': 'Quinazolines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'jjcurtin@wisc.edu', 'phone': '608-262-0387', 'title': 'John Curtin', 'organization': 'University of Wisconsin'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': '8 weeks', 'eventGroups': [{'id': 'EG000', 'title': 'Doxazosin', 'description': 'Participants receive 8 weeks of doxazosin (8mg target dose).\n\nDoxazosin: Doxazosin', 'otherNumAtRisk': 29, 'deathsNumAtRisk': 29, 'otherNumAffected': 24, 'seriousNumAtRisk': 29, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Placebo', 'description': 'Participants will receive 8 weeks of matched placebo.\n\nPlacebo: Placebo', 'otherNumAtRisk': 32, 'deathsNumAtRisk': 32, 'otherNumAffected': 28, 'seriousNumAtRisk': 32, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Orthostatic hypertension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numEvents': 24, 'numAffected': 14}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 18, 'numAffected': 7}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numEvents': 17, 'numAffected': 9}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 9, 'numAffected': 7}], 'organSystem': 'Ear and labyrinth disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Cardiac arrhythmia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numEvents': 12, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 7, 'numAffected': 6}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Chest pains', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numEvents': 5, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numEvents': 38, 'numAffected': 15}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 36, 'numAffected': 17}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Edema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numEvents': 6, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Rhinitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numEvents': 29, 'numAffected': 13}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 9, 'numAffected': 5}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numEvents': 25, 'numAffected': 9}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 17, 'numAffected': 11}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Dyspnea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 5, 'numAffected': 3}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Dry mouth', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numEvents': 30, 'numAffected': 10}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 15, 'numAffected': 8}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Nausea or diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numEvents': 14, 'numAffected': 9}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 9, 'numAffected': 8}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Blurry vision', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Polyurea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numEvents': 6, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 8, 'numAffected': 4}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'General symptoms, nonspecific', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numEvents': 9, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 32, 'numEvents': 10, 'numAffected': 6}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Priapism', 'notes': 'This was only assessed in men', 'stats': [{'groupId': 'EG000', 'numAtRisk': 19, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 20, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Reproductive system and breast disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Startle Potentiation During Stress Reactivity Task', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '17', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Doxazosin', 'description': 'Participants receive 8 weeks of doxazosin (8mg target dose).\n\nDoxazosin: Doxazosin'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Participants will receive 8 weeks of matched placebo.\n\nPlacebo: Placebo'}], 'classes': [{'title': 'Unpredictable startle potentiation', 'categories': [{'measurements': [{'value': '22.25', 'spread': '20.18', 'groupId': 'OG000'}, {'value': '20.76', 'spread': '23.21', 'groupId': 'OG001'}]}]}, {'title': 'Predictable startle potentiation', 'categories': [{'measurements': [{'value': '26.22', 'spread': '30.90', 'groupId': 'OG000'}, {'value': '22.21', 'spread': '35.93', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '4 weeks', 'description': 'Startle potentiation is used to study anxiety and fear with No-shock, Predictable-shock, Unpredictable-shock (NPU) task; a common, well-validated laboratory stressor task. In the Predictable condition of the NPU task, shocks are 100 percent predictable and occur at a consistent, known time. In the Unpredictable condition of the NPU task, shocks are fully unpredictable. A higher score on startle potentiation means a higher stress reactivity response for the given condition.', 'unitOfMeasure': 'microvolts', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Although all 61 participants were able to provide TLFB data through the end of 8 weeks, the NPU task required that they attend a study visit at 4 weeks. 24 participants (10 in doxazosin, 13 in placebo) did not complete that study visit and so have data missing for this outcome measure. 1 (doxazosin) attended the visit but chose not to complete the NPU task. 2 participants (both placebo) completed NPU at this visit, but their NPU data was unusable for this analysis due to technical issues.'}, {'type': 'PRIMARY', 'title': 'Number of Participants Reporting Any Heavy Drinking Days', 'denoms': [{'units': 'Participants', 'counts': [{'value': '29', 'groupId': 'OG000'}, {'value': '32', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Doxazosin', 'description': 'Participants receive 8 weeks of doxazosin (8mg target dose).\n\nDoxazosin: Doxazosin'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Participants will receive 8 weeks of matched placebo.\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '17', 'groupId': 'OG000'}, {'value': '21', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '8 weeks', 'description': 'Timeline-followback (TLFB) was administered twice at 4 weeks and 8 weeks. Participants reported the number of drinks per day for each previous 30 day period. Any heavy drinking was scored "yes" if participant reported any days of heavy drinking (\\> 4/3 standard drinks for men/women) during the total 8 week assessment period; "no" if no heavy drinking was reported', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Doxazosin', 'description': 'Participants receive 8 weeks of doxazosin (8mg target dose).\n\nDoxazosin: Doxazosin'}, {'id': 'FG001', 'title': 'Placebo', 'description': 'Participants will receive 8 weeks of matched placebo.\n\nPlacebo: Placebo'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '29'}, {'groupId': 'FG001', 'numSubjects': '32'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '29'}, {'groupId': 'FG001', 'numSubjects': '32'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Participants were enrolled via community advertisement and clinical referral.', 'preAssignmentDetails': '61 participants were consented, passed medical screening, and were assigned to a drug group.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '29', 'groupId': 'BG000'}, {'value': '32', 'groupId': 'BG001'}, {'value': '61', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Doxazosin', 'description': 'Participants receive 8 weeks of doxazosin (8mg target dose).\n\nDoxazosin: Doxazosin'}, {'id': 'BG001', 'title': 'Placebo', 'description': 'Participants will receive 8 weeks of matched placebo.\n\nPlacebo: Placebo'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '45.6', 'spread': '11.9', 'groupId': 'BG000'}, {'value': '39.7', 'spread': '10.8', 'groupId': 'BG001'}, {'value': '42.5', 'spread': '11.6', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'self report age', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '9', 'groupId': 'BG001'}, {'value': '15', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '23', 'groupId': 'BG000'}, {'value': '23', 'groupId': 'BG001'}, {'value': '46', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '28', 'groupId': 'BG000'}, {'value': '30', 'groupId': 'BG001'}, {'value': '58', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '27', 'groupId': 'BG000'}, {'value': '27', 'groupId': 'BG001'}, {'value': '54', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '29', 'groupId': 'BG000'}, {'value': '32', 'groupId': 'BG001'}, {'value': '61', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'description': 'All participants were enrolled in Madison, WI, USA', 'unitOfMeasure': 'participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-11-07', 'size': 461845, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2021-02-12T15:07', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 61}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-04-12', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-03', 'completionDateStruct': {'date': '2020-03-13', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-03-16', 'studyFirstSubmitDate': '2016-12-01', 'resultsFirstSubmitDate': '2021-02-23', 'studyFirstSubmitQcDate': '2016-12-07', 'lastUpdatePostDateStruct': {'date': '2021-03-18', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2021-03-16', 'studyFirstPostDateStruct': {'date': '2016-12-12', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2021-03-18', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-03-13', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Startle Potentiation During Stress Reactivity Task', 'timeFrame': '4 weeks', 'description': 'Startle potentiation is used to study anxiety and fear with No-shock, Predictable-shock, Unpredictable-shock (NPU) task; a common, well-validated laboratory stressor task. In the Predictable condition of the NPU task, shocks are 100 percent predictable and occur at a consistent, known time. In the Unpredictable condition of the NPU task, shocks are fully unpredictable. A higher score on startle potentiation means a higher stress reactivity response for the given condition.'}, {'measure': 'Number of Participants Reporting Any Heavy Drinking Days', 'timeFrame': '8 weeks', 'description': 'Timeline-followback (TLFB) was administered twice at 4 weeks and 8 weeks. Participants reported the number of drinks per day for each previous 30 day period. Any heavy drinking was scored "yes" if participant reported any days of heavy drinking (\\> 4/3 standard drinks for men/women) during the total 8 week assessment period; "no" if no heavy drinking was reported'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Alcoholism', 'Stress', 'Norepinephrine', 'Doxazosin', 'Anxiety', 'Startle Potentiation', 'Relapse', 'Adrenergic Antagonists', 'Surrogate Endpoint'], 'conditions': ['Alcoholism']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'http://arc.psych.wisc.edu', 'label': "Dr. John Curtin's Addiction Research Center"}]}, 'descriptionModule': {'briefSummary': 'Double-blind, placebo controlled, randomized controlled trial (RCT) for Alcohol Use Disorder examining the effects of doxazosin, a norepinephrine alpha1 receptor antagonist, on stress reactivity and clinical outcomes.', 'detailedDescription': "OBJECTIVES:\n\n1. To translate the preclinical evidence from animal models to stress-induced relapse in humans via direct pharmacological antagonism of the noradrenergic system in abstinent alcoholics with doxazosin, an alpha1 noradrenergic receptor blocker.\n2. To screen the efficacy of doxazosin to target stress-related relapse mechanisms in abstinent alcoholics as a cost-effective first step to repurpose this alpha1 noradrenergic antagonist for relapse prevention in addiction.\n\nPARTICIPANTS:\n\n136 participants with an Alcohol Use Disorder in early abstinence.\n\nSTUDY OVERVIEW:\n\n136 adults with an Alcohol Use Disorder in early abstinence (1-8 weeks abstinent) will participate in a randomized controlled trial (RCT) to examine the efficacy of 8 mg doxazosin (vs. placebo, between-subjects) on stress reactivity and clinical outcome measures (e.g., drinks/week, alcohol craving) during a 8 week treatment period. Doxazosin's impact on stress-related relapse mechanisms will be assessed using a well-validated human model of stressor reactivity (No Shock, Predictable Shock, Unpredictable Shock \\[NPU\\] task) at baseline (pre-treatment) and after 4 weeks of treatment. The NPU task has strong translational ties to both methods (e.g., unpredictable vs. predictable electric shock) and measures (e.g., startle potentiation) from the preclinical literature in animals. This laboratory stress task serves as an attractive early surrogate endpoint post-treatment to assess treatment efficacy and examine stress mechanisms.\n\nAIMS and HYPOTHESIS:\n\nAIM 1: Examine effects of a therapeutic dose of doxazosin on responses to unpredictable stressors in NPU task. The aim is to obtain preliminary evidence via a laboratory surrogate endpoint to repurpose doxazosin for the treatment of stress-induced relapse mechanisms in alcoholism.\n\nPREDICTIONS: Following four weeks of therapeutic dosing, doxazosin (8 mg vs. placebo, between-subjects) will selectively reduce response to unpredictable (vs. predictable) stressors indexed by physiological defensive reactivity (startle potentiation) and self-reported negative affect and craving in abstinent alcoholics.\n\nAIM 2: Examine effects of a therapeutic dose of doxazosin on early clinical outcome measures. The aim is to obtain additional evidence via clinical outcome measures to repurpose doxazosin for the treatment of stress-induced relapse mechanisms in alcoholism.\n\nPREDICTIONS: Following eight weeks of therapeutic dosing, doxazosin (8 mg vs. placebo, between-subjects) will increase continuous abstinence and decrease drinking days per week and drinks per week during the medication treatment period. Doxazosin will also decrease craving measured during the 8th week of medication use when participants have achieved the maximum dose for 4.5 weeks.\n\nAIM 3: Examine predictive validity of pre-treatment laboratory tests of noradrenergic relevant stress-reactivity on surrogate endpoint and clinical outcome measures. The aim is to link individual differences in stress reactivity at baseline (i.e. pre-treatment) to laboratory surrogate endpoints and early clinical outcome measures following therapeutic dosing.\n\nPREDICTIONS: Higher pre-treatment reactivity during unpredictable stressors will predict poorer surrogate endpoint and clinical outcomes overall. Therapeutic 8 mg dose effects of doxazosin will be greater among alcoholics who display higher pre-treatment reactivity to unpredictable stressors.\n\nAIM 4: Examine if the effects of doxazosin on clinical outcome measures are mediated by a reduction of stress-reactivity as measured by the NPU task. The aim is to identify whether reductions in stress-reactivity (NPU task) is the mechanism through which doxazosin has its effect on drinking behavior (clinical outcome).\n\nPREDICTIONS: The direct effect of doxazosin (vs. placebo) following 8 weeks of therapeutic 8 mg dosing on clinical outcomes (e.g., continuous abstinence, drinking days/week, drinks/week) will be partially mediated by the indirect effect of doxazosin on surrogate endpoint of NPU stress reactivity at 4 weeks."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'INCLUSION CRITERIA:\n\n* Diagnostic and Statistical Manual (DSM-5) diagnosis of Alcohol Use Disorder, Moderate-Severe\n* Alcohol abstinent for 1 - 8 weeks\n* Ages of 18 to 65\n\nExclusion criteria are divided into three broad categories of Medical, Psychiatric/Behavioral, and Medications/Therapies.\n\nEXCLUSION CRITERIA: Medical\n\n* Blood alcohol concentration above 0.00.\n* Color blind.\n* Heart rate \\>100 beats per minute after five minutes seated.\n* Heart rate \\<55 beats per minute after five minutes seated.\n* Systolic BP \\<100 after five minutes seated.\n* Systolic BP drop \\>20mm Hg or diastolic BP drop \\>10mm Hg after two minutes standing.\n* Dizziness, lightheadedness, unsteadiness or other problems (e.g, nausea, blurry vision) after two minutes standing.\n* Uncorrected auditory/vision problems.\n* Current treatment for chronic pain condition.\n* Past or current coronary artery disease, cerebrovascular accident, congestive heart failure.\n* Current chronic renal insufficiency, liver insufficiency or moderate hepatic impairment, pancreatitis, immunosuppressive therapy, or cancer with systemic effects or therapy.\n* Benign positional vertigo, Meniere\'s disease, or narcolepsy.\n* Previous allergic or adverse reaction to doxazosin or other alpha1 noradrenergic antagonist.\n* Scheduled or reported plans for cataract surgery prior to study completion.\n* Currently symptomatic of alcohol withdrawal \\[Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) Score \\> 10, or positive for any \'visual, auditory or tactile disturbances,\' or for \'orientation and clouding of sensorium\'\\]\n* Discharged from inpatient treatment for Alcohol Use Disorder or alcohol detoxification within past 7 days.\n* Currently medically unstable.\n* Electrocardiogram (ECG) clinical over-read indicates concerns of cardiac function.\n* Other self-reported acute or unstable illness that, in the opinion of the study team, would preclude a safe and reliable study participation\n\nEXCLUSION CRITERIA: Female Participants Only\n\n* Non-negative urine pregnancy test.\n* Women of childbearing potential (see definition below) must agree to use one of the following forms of birth control until after study completion. Acceptable birth control is defined as the following methods of contraception: abstinence; hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy of partner and tubal ligation; "single" barrier methods of contraception (e.g. male condom, female condom, cervical cap, diaphragm, contraceptive sponge) with use of spermicide; or "double barrier" method of contraception (e.g. male condom with diaphragm, male condom with cervical cap).\n* Breastfeeding.\n\nNOTE: Women of childbearing potential are females who have experienced menarche and do not meet the criteria for women not of childbearing potential. Women not of childbearing potential are females who are permanently sterile (e.g., hysterectomy, bilateral oophorectomy) or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause.\n\nEXCLUSION CRITERIA: Psychological/Behavioral\n\n* Self-reported lifetime diagnosis of schizophrenia, schizoaffective disorder, psychotic disorder not otherwise specified, bipolar disorder (with manic episode), borderline personality disorder, or any neurocognitive disorder that may impair a reliable, safe participation.\n* Current suicidal ideation.\n* Current active substance use disorder other than alcohol or tobacco.\n\nEXCLUSION CRITERIA: Medications/Therapies\n\n* Currently prescribed or used within past week: doxazosin or other alpha1 noradrenergic antagonist (e.g., prazosin, terazosin).\n* Currently prescribed or used within past week: substances with stimulant properties (e.g., d-amphetamine, methylphenidate, ephedra, pseudoephedrine).\n* Currently prescribed or used within past week: Sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra).\n* Currently prescribed or used within past week: beta-blockers (e.g., propanolol), alpha2 agonists (e.g., clonidine, guanfacine, dexmedetomidine), and serotonin and norepinephrine reuptake inhibitors (SNRI) (e.g., venlafaxine, duloxetine, atomoxetine, viloxazine).\n* Currently used daily or used within past week: alpha1 agonists (e.g., midodrine, metaraminol, oxymetazoline, phenylephrine).\n* Currently used daily or used within past week: Benzodiazepines (e.g., diazepam, chlordiazepoxide, lorazepam, clonazepam, alprazolam), zolpidem (Ambien), zaleplon (Sonata), zopiclone (Imovane), eszopiclone (Lunesta), doxepin (Silenor).\n* Currently prescribed and used daily or used within past 2 weeks: Trazodone.\n* Currently prescribed or used within 2 weeks: Disulfiram (Antabuse).'}, 'identificationModule': {'nctId': 'NCT02989493', 'briefTitle': 'Testing Doxazosin to Treat Stress Mechanisms in Alcoholism', 'organization': {'class': 'OTHER', 'fullName': 'University of Wisconsin, Madison'}, 'officialTitle': 'Randomized Controlled Trial Targeting Noradrenergic Stress Mechanisms in Alcoholism With Doxazosin', 'orgStudyIdInfo': {'id': '2015-1009'}, 'secondaryIdInfos': [{'id': 'R01AA024388', 'link': 'https://reporter.nih.gov/quickSearch/R01AA024388', 'type': 'NIH'}, {'id': 'A487400', 'type': 'OTHER', 'domain': 'UW Madison'}, {'id': 'L&S\\PSYCHOLOGY\\PSYCHOLOGY', 'type': 'OTHER', 'domain': 'UW Madison'}, {'id': 'Protocol Version 11/7/2019', 'type': 'OTHER', 'domain': 'UW Madison'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Doxazosin', 'description': 'Participants receive 8 weeks of doxazosin (8mg target dose).', 'interventionNames': ['Drug: Doxazosin']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Participants will receive 8 weeks of matched placebo.', 'interventionNames': ['Other: Placebo']}], 'interventions': [{'name': 'Doxazosin', 'type': 'DRUG', 'description': 'Doxazosin', 'armGroupLabels': ['Doxazosin']}, {'name': 'Placebo', 'type': 'OTHER', 'description': 'Placebo', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '53706', 'city': 'Madison', 'state': 'Wisconsin', 'country': 'United States', 'facility': 'University of Wisconsin', 'geoPoint': {'lat': 43.07305, 'lon': -89.40123}}], 'overallOfficials': [{'name': 'John J Curtin, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Wisconsin, Madison'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES', 'description': 'Data will be made available online upon study completion at the Open Science Framework: https://osf.io'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Wisconsin, Madison', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institute on Alcohol Abuse and Alcoholism (NIAAA)', 'class': 'NIH'}], 'responsibleParty': {'type': 'SPONSOR'}}}}