Ignite Creation Date:
2025-12-25 @ 4:46 AM
Ignite Modification Date:
2025-12-26 @ 3:48 AM
Study NCT ID:
NCT01132118
Status:
COMPLETED
Last Update Posted:
2014-09-03
First Post:
2010-05-25
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Hydroxychloroquine to Improve Insulin Sensitivity in Rheumatoid Arthritis
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001172', 'term': 'Arthritis, Rheumatoid'}, {'id': 'D007333', 'term': 'Insulin Resistance'}], 'ancestors': [{'id': 'D001168', 'term': 'Arthritis'}, {'id': 'D007592', 'term': 'Joint Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D012216', 'term': 'Rheumatic Diseases'}, {'id': 'D003240', 'term': 'Connective Tissue Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D006946', 'term': 'Hyperinsulinism'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D006886', 'term': 'Hydroxychloroquine'}], 'ancestors': [{'id': 'D002738', 'term': 'Chloroquine'}, {'id': 'D000634', 'term': 'Aminoquinolines'}, {'id': 'D011804', 'term': 'Quinolines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'dsolomon@partners.org', 'phone': '617-525-8127', 'title': 'Dr. Daniel H. Solomon', 'organization': "Brigham and Women's Hospital"}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Hydroxychloroquine', 'description': "Participants received hydroxychloroquine (HCQ) for 8 weeks.\n\nHydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.", 'otherNumAtRisk': 15, 'otherNumAffected': 2, 'seriousNumAtRisk': 15, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Placebo', 'description': 'Participants received Placebo tablets for 8 weeks.', 'otherNumAtRisk': 15, 'otherNumAffected': 0, 'seriousNumAtRisk': 15, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Rash', 'notes': '1 participants developed a rash when taking HCQ.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 15, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders'}, {'term': 'Liver Function Test Abnormality', 'notes': '1 patient had abnormal liver function test scores while taking HCQ.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 15, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Insulin Sensitivity Index', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Hydroxychloroquine', 'description': "This group contains results for when study participants were taking hydroxychlorquine.\n\nHydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg."}, {'id': 'OG001', 'title': 'Placebo', 'description': 'This arm group contains the results for patients while they were on placebo.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '7.7', 'spread': '4.8', 'groupId': 'OG000'}, {'value': '7.7', 'spread': '4.8', 'groupId': 'OG001'}]}]}, {'title': 'Period Value', 'categories': [{'measurements': [{'value': '8.1', 'spread': '4.5', 'groupId': 'OG000'}, {'value': '7.8', 'spread': '4.0', 'groupId': 'OG001'}]}]}, {'title': 'Change', 'categories': [{'measurements': [{'value': '0.4', 'spread': '2.9', 'groupId': 'OG000'}, {'value': '0.14', 'spread': '3.1', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.930', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Unadjusted', 'groupDescription': 'The P-value calculated was for the difference betweeen the change during hydroxychloroquine versus placebo using Wilcoxon signed-rank tests.', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.785', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Adjusted for weight change.', 'groupDescription': 'The P-value was calculated for the difference between the change during hydroxychloroquine versus placebo from a linear regression model.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and Week 8', 'description': 'We will examine the effect of HCQ on the Matsuda Insulin Sensitivity Index (ISI) during the active treatment phase compared with placebo phase.\n\nISI is based on insulin and glucose levels in a fasting state during an oral glucose tolerance test (OGTT) and is calculated as follows:\n\nISI (Matsuda) = 10000/√ G0 X I0 X Gmean X Imean\n\nG0 - fasting plasma glucose (mg/dL) I0 - fasting plasma insulin (mIU/L) Gmean - mean plasma glucose during OGTT (mg/dL) Imean - mean plasma insulin during OGTT (mIU/L)', 'unitOfMeasure': '(dL x L)/(mg x mIU)', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'HOMA-IR', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Hydroxychloroquine', 'description': "This group contains results for when study participants were taking hydroxychlorquine.\n\nHydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg."}, {'id': 'OG001', 'title': 'Placebo', 'description': 'This arm group contains the results for patients while they were on placebo.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '2.0', 'spread': '1.7', 'groupId': 'OG000'}, {'value': '2.0', 'spread': '1.7', 'groupId': 'OG001'}]}]}, {'title': 'Period', 'categories': [{'measurements': [{'value': '1.7', 'spread': '1.0', 'groupId': 'OG000'}, {'value': '1.6', 'spread': '0.79', 'groupId': 'OG001'}]}]}, {'title': 'Change', 'categories': [{'measurements': [{'value': '-0.3', 'spread': '1.5', 'groupId': 'OG000'}, {'value': '-0.42', 'spread': '1.4', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.575', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Unadjusted P-value', 'groupDescription': 'P-value for the difference between change during hydroxychloroquine versus placebo using Wilcoxon signed-rank tests.', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.308', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Adjusted for weight change.', 'groupDescription': 'P-value for the difference between the change during hydroxychloroquine versus placebo from a linear regression model.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and Week 8', 'description': 'We will examine the effect of HCQ on HOMA-IR during the active treatment phase compared with placebo phase.\n\nHOMA-IR = (Glucose x insulin)/405', 'unitOfMeasure': '(mg x mIU)/(dL*L)', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'HOMA-B', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Hydroxychloroquine', 'description': "This group contains results for when study participants were taking hydroxychlorquine.\n\nHydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg."}, {'id': 'OG001', 'title': 'Placebo', 'description': 'This arm group contains the results for patients while they were on placebo.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '116.5', 'spread': '100.4', 'groupId': 'OG000'}, {'value': '116.5', 'spread': '100.4', 'groupId': 'OG001'}]}]}, {'title': 'Period', 'categories': [{'measurements': [{'value': '110.8', 'spread': '81.6', 'groupId': 'OG000'}, {'value': '109.7', 'spread': '82.6', 'groupId': 'OG001'}]}]}, {'title': 'Change', 'categories': [{'measurements': [{'value': '-5.8', 'spread': '72.9', 'groupId': 'OG000'}, {'value': '-6.8', 'spread': '78.0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.468', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Unadjusted', 'groupDescription': 'P-value for the difference betweeen change during hydroxychloroquine versus placebo suing Wilcoxon signed-rank tests.', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.902', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Adjusted for weight change.', 'groupDescription': 'P-value for the difference between the change during hydroxychloroquine versus placebo from a linear regression model.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and Week 8', 'description': 'HOMA-B = (360 x Insulin)/(Glucose - 63)', 'unitOfMeasure': '(mIU x dL)/(L x mg)', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Total Cholesterol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Hydroxychloroquine', 'description': "This group contains results for when study participants were taking hydroxychlorquine.\n\nHydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg."}, {'id': 'OG001', 'title': 'Placebo', 'description': 'This arm group contains the results for patients while they were on placebo.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '192.4', 'spread': '37.5', 'groupId': 'OG000'}, {'value': '192.4', 'spread': '37.5', 'groupId': 'OG001'}]}]}, {'title': 'Period', 'categories': [{'measurements': [{'value': '179.7', 'spread': '44.3', 'groupId': 'OG000'}, {'value': '189.4', 'spread': '37.9', 'groupId': 'OG001'}]}]}, {'title': 'Change', 'categories': [{'measurements': [{'value': '-12.7', 'spread': '20.0', 'groupId': 'OG000'}, {'value': '-3.0', 'spread': '22.4', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.004', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Unadjusted', 'groupDescription': 'P-value for the difference between the change during hydroxychloroquine versus placebo using Wilcoxon signed-rank tests.', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.004', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Adjusted for weight change.', 'groupDescription': 'P-value for the difference between the change during hydroxychloroquine versus placebo from a linear regression model.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and Week 8', 'description': 'mg/dL', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'LDL Cholesterol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Hydroxychloroquine', 'description': "This group contains results for when study participants were taking hydroxychlorquine.\n\nHydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg."}, {'id': 'OG001', 'title': 'Placebo', 'description': 'This arm group contains the results for patients while they were on placebo.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '114.1', 'spread': '29.8', 'groupId': 'OG000'}, {'value': '114.1', 'spread': '29.8', 'groupId': 'OG001'}]}]}, {'title': 'Period', 'categories': [{'measurements': [{'value': '101.7', 'spread': '36.7', 'groupId': 'OG000'}, {'value': '109.9', 'spread': '33.1', 'groupId': 'OG001'}]}]}, {'title': 'Change', 'categories': [{'measurements': [{'value': '-12.4', 'spread': '20.1', 'groupId': 'OG000'}, {'value': '-4.2', 'spread': '17.7', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.009', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Unadjusted', 'groupDescription': 'P-value for the difference between the change during hydroxychloroquine versus placebo using Wilcoxon signed-rank tests.', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.011', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Adjusted for weight change.', 'groupDescription': 'P-value for the difference between the change during hydroxychloroquine versus placebo from a linear regression model.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and Week 8', 'description': 'mg/dL', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'HDL Cholesterol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Hydroxychloroquine', 'description': "This group contains results for when study participants were taking hydroxychlorquine.\n\nHydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg."}, {'id': 'OG001', 'title': 'Placebo', 'description': 'This arm group contains the results for patients while they were on placebo.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '58.1', 'spread': '17.9', 'groupId': 'OG000'}, {'value': '58.1', 'spread': '17.9', 'groupId': 'OG001'}]}]}, {'title': 'Period', 'categories': [{'measurements': [{'value': '59.4', 'spread': '18.2', 'groupId': 'OG000'}, {'value': '60.3', 'spread': '17.8', 'groupId': 'OG001'}]}]}, {'title': 'Change', 'categories': [{'measurements': [{'value': '1.3', 'spread': '6.7', 'groupId': 'OG000'}, {'value': '2.2', 'spread': '9.8', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.730', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Unadjusted', 'groupDescription': 'P-value for the difference between the change during hydroxychloroquine versus placebo using Wilcoxon signed-rank tests.', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.208', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Adjusted for weight change.', 'groupDescription': 'P-value for the difference between the change during hydroxychloroquine versus placebo from a linear regression model.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and Week 8', 'description': 'mg/dL', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Triglycerides', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Hydroxychloroquine', 'description': "This group contains results for when study participants were taking hydroxychlorquine.\n\nHydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg."}, {'id': 'OG001', 'title': 'Placebo', 'description': 'This arm group contains the results for patients while they were on placebo.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '100.6', 'spread': '44.0', 'groupId': 'OG000'}, {'value': '100.6', 'spread': '44.0', 'groupId': 'OG001'}]}]}, {'title': 'Period', 'categories': [{'measurements': [{'value': '92.4', 'spread': '41.7', 'groupId': 'OG000'}, {'value': '95.6', 'spread': '44.9', 'groupId': 'OG001'}]}]}, {'title': 'Change', 'categories': [{'measurements': [{'value': '-8.2', 'spread': '45.0', 'groupId': 'OG000'}, {'value': '-5.0', 'spread': '20.1', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.487', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Unadjusted P-value.', 'groupDescription': 'P-value for the difference between the change during hydroxychloroquine versus placebo using Wilcoxon signed-rank tests.', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '0.884', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'P-value adjusted for weight change.', 'groupDescription': 'P-value for the difference between the change during hydroxycholorquine versus placebo from a linear regression model.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and Week 8', 'description': 'mg/dL', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'HCQ Then Placebo', 'description': "This arm of the study contains half the study population after randomization. The participants in this arm received hydroxychloroquine for 8 weeks and then crossed over to a placebo for 8 weeks. Study staff was blinded to which order they were taking the hydroxychloroquine and placebo in.\n\nHydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg."}, {'id': 'FG001', 'title': 'Placebo Then HCQ', 'description': "This arm of the study contains half the study population after randomization. The participants in this arm received hydroxychloroquine for 8 weeks and then crossed over to a placebo for 8 weeks. Study staff was blinded to which order they were taking the hydroxychloroquine and placebo in.\n\nHydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg."}], 'periods': [{'title': 'First Intervention (8 Weeks)', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '15'}, {'groupId': 'FG001', 'numSubjects': '15'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '3'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '3'}]}]}, {'title': 'Second Intervention (8 Weeks)', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '11'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}], 'recruitmentDetails': '107 potentially eligible RA patients were screened during 2010-2011. 7 subjects did not meet inclusion/exclusion criteria at screening and 63 declined participation.', 'preAssignmentDetails': '37 subjects were initially consented, 7 withdrew consent before randomization. Thirty patients were randomized. Five patients withdrew consent after randomization and two patients stopped participation in the study due to non-serious adverse events.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'BG000'}, {'value': '15', 'groupId': 'BG001'}, {'value': '30', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'HCQ Then Placebo', 'description': "This arm of the study contains half the study population after randomization. The participants in this arm received hydroxychloroquine for 8 weeks and then crossed over to a placebo for 8 weeks. Study staff was blinded to which order they were taking the hydroxychloroquine and placebo in.\n\nHydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg."}, {'id': 'BG001', 'title': 'Placebo Then HCQ', 'description': "This arm of the study contains half the study population after randomization. The participants in this arm received hydroxychloroquine for 8 weeks and then crossed over to a placebo for 8 weeks. Study staff was blinded to which order they were taking the hydroxychloroquine and placebo in.\n\nHydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg."}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '56', 'spread': '14', 'groupId': 'BG000'}, {'value': '57', 'spread': '14', 'groupId': 'BG001'}, {'value': '56.5', 'spread': '11', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '13', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '27', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'Participants who were randomized to receive either HCQ or placebo.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 30}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-06'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2014-09', 'completionDateStruct': {'date': '2012-06', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2014-09-02', 'studyFirstSubmitDate': '2010-05-25', 'resultsFirstSubmitDate': '2014-08-08', 'studyFirstSubmitQcDate': '2010-05-26', 'lastUpdatePostDateStruct': {'date': '2014-09-03', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2014-09-02', 'studyFirstPostDateStruct': {'date': '2010-05-27', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2014-09-03', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2012-04', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Insulin Sensitivity Index', 'timeFrame': 'Baseline and Week 8', 'description': 'We will examine the effect of HCQ on the Matsuda Insulin Sensitivity Index (ISI) during the active treatment phase compared with placebo phase.\n\nISI is based on insulin and glucose levels in a fasting state during an oral glucose tolerance test (OGTT) and is calculated as follows:\n\nISI (Matsuda) = 10000/√ G0 X I0 X Gmean X Imean\n\nG0 - fasting plasma glucose (mg/dL) I0 - fasting plasma insulin (mIU/L) Gmean - mean plasma glucose during OGTT (mg/dL) Imean - mean plasma insulin during OGTT (mIU/L)'}], 'secondaryOutcomes': [{'measure': 'HOMA-IR', 'timeFrame': 'Baseline and Week 8', 'description': 'We will examine the effect of HCQ on HOMA-IR during the active treatment phase compared with placebo phase.\n\nHOMA-IR = (Glucose x insulin)/405'}, {'measure': 'HOMA-B', 'timeFrame': 'Baseline and Week 8', 'description': 'HOMA-B = (360 x Insulin)/(Glucose - 63)'}, {'measure': 'Total Cholesterol', 'timeFrame': 'Baseline and Week 8', 'description': 'mg/dL'}, {'measure': 'LDL Cholesterol', 'timeFrame': 'Baseline and Week 8', 'description': 'mg/dL'}, {'measure': 'HDL Cholesterol', 'timeFrame': 'Baseline and Week 8', 'description': 'mg/dL'}, {'measure': 'Triglycerides', 'timeFrame': 'Baseline and Week 8', 'description': 'mg/dL'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['rheumatoid arthritis', 'insulin resistance', 'hydroxychloroquine', 'cholesterol'], 'conditions': ['Rheumatoid Arthritis', 'Insulin Resistance']}, 'referencesModule': {'references': [{'pmid': '10480510', 'type': 'BACKGROUND', 'citation': 'Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999 Sep;22(9):1462-70. doi: 10.2337/diacare.22.9.1462.'}, {'pmid': '15289378', 'type': 'BACKGROUND', 'citation': 'Reilly MP, Wolfe ML, Rhodes T, Girman C, Mehta N, Rader DJ. Measures of insulin resistance add incremental value to the clinical diagnosis of metabolic syndrome in association with coronary atherosclerosis. Circulation. 2004 Aug 17;110(7):803-9. doi: 10.1161/01.CIR.0000138740.84883.9C. Epub 2004 Aug 2.'}, {'pmid': '12087016', 'type': 'BACKGROUND', 'citation': 'Hanley AJ, Williams K, Stern MP, Haffner SM. Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the San Antonio Heart Study. Diabetes Care. 2002 Jul;25(7):1177-84. doi: 10.2337/diacare.25.7.1177.'}, {'pmid': '8566109', 'type': 'BACKGROUND', 'citation': "Glaser K, Sung ML, O'Neill K, Belfast M, Hartman D, Carlson R, Kreft A, Kubrak D, Hsiao CL, Weichman B. Etodolac selectively inhibits human prostaglandin G/H synthase 2 (PGHS-2) versus human PGHS-1. Eur J Pharmacol. 1995 Jul 25;281(1):107-11. doi: 10.1016/0014-2999(95)00302-2."}, {'pmid': '11396092', 'type': 'BACKGROUND', 'citation': 'Gabriel SE. The epidemiology of rheumatoid arthritis. Rheum Dis Clin North Am. 2001 May;27(2):269-81. doi: 10.1016/s0889-857x(05)70201-5.'}, {'pmid': '16908509', 'type': 'BACKGROUND', 'citation': 'Young A, Koduri G, Batley M, Kulinskaya E, Gough A, Norton S, Dixey J; Early Rheumatoid Arthritis Study (ERAS) group. Mortality in rheumatoid arthritis. Increased in the early course of disease, in ischaemic heart disease and in pulmonary fibrosis. Rheumatology (Oxford). 2007 Feb;46(2):350-7. doi: 10.1093/rheumatology/kel253. Epub 2006 Aug 14.'}, {'pmid': '15843450', 'type': 'BACKGROUND', 'citation': 'Goodson N, Marks J, Lunt M, Symmons D. Cardiovascular admissions and mortality in an inception cohort of patients with rheumatoid arthritis with onset in the 1980s and 1990s. Ann Rheum Dis. 2005 Nov;64(11):1595-601. doi: 10.1136/ard.2004.034777. Epub 2005 Apr 20.'}, {'pmid': '12628952', 'type': 'BACKGROUND', 'citation': 'Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, Stampfer MJ, Curhan GC. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation. 2003 Mar 11;107(9):1303-7. doi: 10.1161/01.cir.0000054612.26458.b2.'}, {'pmid': '15751097', 'type': 'BACKGROUND', 'citation': 'Maradit-Kremers H, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE. Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum. 2005 Mar;52(3):722-32. doi: 10.1002/art.20878.'}, {'pmid': '15529391', 'type': 'BACKGROUND', 'citation': 'Solomon DH, Curhan GC, Rimm EB, Cannuscio CC, Karlson EW. Cardiovascular risk factors in women with and without rheumatoid arthritis. Arthritis Rheum. 2004 Nov;50(11):3444-9. doi: 10.1002/art.20636.'}, {'pmid': '11368701', 'type': 'BACKGROUND', 'citation': 'Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA. 2001 May 16;285(19):2481-5. doi: 10.1001/jama.285.19.2481.'}, {'pmid': '16947779', 'type': 'BACKGROUND', 'citation': 'Dessein PH, Joffe BI. Insulin resistance and impaired beta cell function in rheumatoid arthritis. Arthritis Rheum. 2006 Sep;54(9):2765-75. doi: 10.1002/art.22053.'}, {'pmid': '18576352', 'type': 'BACKGROUND', 'citation': 'Chung CP, Oeser A, Solus JF, Gebretsadik T, Shintani A, Avalos I, Sokka T, Raggi P, Pincus T, Stein CM. Inflammation-associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms. Arthritis Rheum. 2008 Jul;58(7):2105-12. doi: 10.1002/art.23600.'}, {'pmid': '3069509', 'type': 'BACKGROUND', 'citation': 'Quatraro A, Consoli G, Ceriello A, Giugliano D. Is there a role for chloroquine treatment in diabetes? A three case report. Diabete Metab. 1988 Sep-Oct;14(5):666-7. No abstract available.'}, {'pmid': '3888217', 'type': 'BACKGROUND', 'citation': 'Garcia-Webb P, Bonser AM. Insulin binding and degradation in isolated hepatocytes from streptozotocin injected rats. Biochem Biophys Res Commun. 1985 Apr 30;128(2):487-93. doi: 10.1016/0006-291x(85)90073-7.'}, {'pmid': '10072192', 'type': 'BACKGROUND', 'citation': 'Emami J, Pasutto FM, Mercer JR, Jamali F. Inhibition of insulin metabolism by hydroxychloroquine and its enantiomers in cytosolic fraction of liver homogenates from healthy and diabetic rats. Life Sci. 1999;64(5):325-35. doi: 10.1016/s0024-3205(98)00568-2.'}, {'pmid': '2110430', 'type': 'BACKGROUND', 'citation': 'Quatraro A, Consoli G, Magno M, Caretta F, Nardozza A, Ceriello A, Giugliano D. Hydroxychloroquine in decompensated, treatment-refractory noninsulin-dependent diabetes mellitus. A new job for an old drug? Ann Intern Med. 1990 May 1;112(9):678-81. doi: 10.7326/0003-4819-112-9-678.'}, {'pmid': '11850097', 'type': 'BACKGROUND', 'citation': 'Gerstein HC, Thorpe KE, Taylor DW, Haynes RB. The effectiveness of hydroxychloroquine in patients with type 2 diabetes mellitus who are refractory to sulfonylureas--a randomized trial. Diabetes Res Clin Pract. 2002 Mar;55(3):209-19. doi: 10.1016/s0168-8227(01)00325-4.'}, {'pmid': '17622600', 'type': 'BACKGROUND', 'citation': 'Wasko MC, Hubert HB, Lingala VB, Elliott JR, Luggen ME, Fries JF, Ward MM. Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. JAMA. 2007 Jul 11;298(2):187-93. doi: 10.1001/jama.298.2.187.'}, {'pmid': '24470436', 'type': 'DERIVED', 'citation': 'Solomon DH, Garg R, Lu B, Todd DJ, Mercer E, Norton T, Massarotti E. Effect of hydroxychloroquine on insulin sensitivity and lipid parameters in rheumatoid arthritis patients without diabetes mellitus: a randomized, blinded crossover trial. Arthritis Care Res (Hoboken). 2014 Aug;66(8):1246-51. doi: 10.1002/acr.22285.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to determine whether hydroxychloroquine (HCQ) reduces insulin resistance in non-diabetic subjects with rheumatoid arthritis (RA). The investigators will conduct a double-blind randomized crossover trial in subjects with RA to test the hypothesis that HCQ improves insulin sensitivity. The investigators will also use data from the trial to identify determinants of insulin resistance in RA. The investigators hypothesize that RA will be associated with an increased risk of insulin resistance and that independent risk factors for increased insulin resistance in RA include higher BMI, elevated acute phase reactants, greater fat to muscle ratio, and less physical activity.', 'detailedDescription': 'Our ability to better control the pain and disability of rheumatoid arthritis (RA) now focuses attention on reducing the impact of RA-associated comorbidities. The most common cause of death in RA is cardiovascular (CV) disease, and the risk of myocardial infarction and stroke are approximately doubled in RA. The determinants of CV risk in RA include traditional CV risk factors as well as aspects of the inflammatory process defining RA. It is likely that RA-associated inflammation accelerates atherosclerosis through direct effects on the endothelium as well as indirect effects on insulin metabolism. Several studies report an increased prevalence of insulin resistance among persons with RA. However, it is not clear whether the inflammation of RA causes insulin resistance. Corticosteroids and abnormalities in the hypothalamic-pituitary axis may also contribute to abnormal glucose metabolism. Little information is available to guide management of a pre-diabetic insulin resistance state in RA.\n\nHydroxychloroquine (HCQ), a commonly used medicine early in RA, may play a role in improving insulin resistance. Several previous trials demonstrated the ability of HCQ to reduce blood glucose levels in diabetics, and a large epidemiologic study found that subjects with RA using HCQ were less likely to develop diabetes. In animal models, anti-malarials lower blood glucose through slowing insulin metabolism.\n\nWith CV disease a major comorbidity in RA and insulin resistance possibly a major determinant of CV risk, intervention studies need to begin to translate prior work into clinical therapeutics.\n\nRelevance: If this study demonstrates a beneficial effect of HCQ on insulin resistance among the randomized subjects, this would provide strong evidence that HCQ has benefits beyond RA and SLE disease activity. Currently, HCQ is stopped in many patients as they "step-up" to more aggressive DMARD treatments, or HCQ may never be tried in some patients who present with RA carrying with poor prognosis. If HCQ improves insulin sensitivity, there may be rationale for continuing HCQ chronically in patients with RA. As well, a larger clinical endpoint study would be strongly considered.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Age 18 or older\n* Able to provide informed consent and comply with study visits\n* Hemoglobin ≥ 10 g/dL (within last two months)\n* WBC ≥ 4 K/uL (within last two months)\n* Platelet count ≥ 150 ≤ 450 K/uL (within last two months)\n* (GFR) Creatinine clearance ≥ 70 ml/min (MDRD) (within last two months)\n* SGOT, SGPT ≤ 1.5 times upper limits of normal (within last two months)\n* Normal eye exam within 12 months of study entry (copy of letter from subject's ophthalmologist or optometrist stating that the subject has no evidence of macular pathology)\n* Diagnosis of rheumatoid arthritis\n\nExclusion Criteria:\n\n* History of any neuromuscular disease including muscular dystrophy, metabolic myopathies, peripheral neuropathy, multiple sclerosis, and other myopathies or myositides\n* History of diabetes or fasting plasma glucose of 126 mg/dl or greater\n* History of any untoward reaction to antimalarials\n* Uncontrolled hypertension (\\>140/90)\n* History of any ophthalmologic disease except for glaucoma or cataracts\n* Planned elective surgery during the study period\n* Digoxin therapy\n* Treatment with corticosteroids (\\> 5 mg) for any disorder\n* History of psoriasis\n* Any chronic disease that in the opinion of the investigator warrants exclusion (e.g. inflammatory bowel disease, malignancy other than basal cell carcinoma, chronic liver disease)\n* History of chronic intestinal disorders (Crohn's disease, ulcerative colitis, celiac sprue, collagenous colitis, eosinophilic enteritis)\n* Creatinine clearance ≤ 60 ml/min (MDRD) (within last two months)\n* Hemoglobin ≤ 10 g/dL (within last two months)\n* WBC ≤ 4 K/uL (within last two months)\n* Platelet count ≤ 150 ≥ 450 K/uL (within last two months)\n* SGOT, SGPT ≥ 1.5 times upper limits of normal (within last two months)\n* Women who are pregnant or breastfeeding"}, 'identificationModule': {'nctId': 'NCT01132118', 'acronym': 'RA PLUS', 'briefTitle': 'Hydroxychloroquine to Improve Insulin Sensitivity in Rheumatoid Arthritis', 'organization': {'class': 'OTHER', 'fullName': "Brigham and Women's Hospital"}, 'officialTitle': 'Hydroxychloroquine to Improve Insulin Sensitivity in Rheumatoid Arthritis', 'orgStudyIdInfo': {'id': '2009P001926'}, 'secondaryIdInfos': [{'id': 'R21AR057924', 'link': 'https://reporter.nih.gov/quickSearch/R21AR057924', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'OTHER', 'label': 'Placebo then HCQ', 'description': 'This arm of the study will contain half the study population after randomization. The participants in this arm will receive hydroxychloroquine for 8 weeks and then crossover to a placebo for 8 weeks. Study staff will be blinded to which order they are taking the hydroxychloroquine and placebo in.', 'interventionNames': ['Drug: Hydroxychloroquine']}, {'type': 'OTHER', 'label': 'HCQ then Placebo', 'description': 'This arm of the study will contain half the study population after randomization. The participants in this arm will receive hydroxychloroquine for 8 weeks and then crossover to a placebo for 8 weeks. Study staff will be blinded to which order they are taking the hydroxychloroquine and placebo in.', 'interventionNames': ['Drug: Hydroxychloroquine']}], 'interventions': [{'name': 'Hydroxychloroquine', 'type': 'DRUG', 'otherNames': ['Plaquenil'], 'description': "Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.", 'armGroupLabels': ['HCQ then Placebo', 'Placebo then HCQ']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02115', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': "Brigham and Women's Hospital", 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}], 'overallOfficials': [{'name': 'Daniel H Solomon, MD, MPH', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Brigham and Women's Hospital"}, {'name': 'Elena M Massarotti, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Brigham and Women's Hospital"}, {'name': 'Rajesh K Garg, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Brigham and Women's Hospital"}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "Brigham and Women's Hospital", 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Director of Clinical Sciences', 'investigatorFullName': 'Daniel H. Solomon, M.D.,MPH', 'investigatorAffiliation': "Brigham and Women's Hospital"}}}}