{
  "FullStudy":{
    "Rank":217767,
    "Study":{
      "ProtocolSection":{
        "IdentificationModule":{
          "NCTId":"NCT01517100",
          "OrgStudyIdInfo":{
            "OrgStudyId":"999912018"
          },
          "SecondaryIdInfoList":{
            "SecondaryIdInfo":[
              {
                "SecondaryId":"12-AG-N018"
              }
            ]
          },
          "Organization":{
            "OrgFullName":"National Institutes of Health Clinical Center (CC)",
            "OrgClass":"NIH"
          },
          "BriefTitle":"The Role of Endocannabinoids in Insulin Production and Action",
          "OfficialTitle":"The Roles of Endocannabinoids in Insulin Secretion and Action"
        },
        "StatusModule":{
          "StatusVerifiedDate":"November 26, 2019",
          "OverallStatus":"Completed",
          "ExpandedAccessInfo":{
            "HasExpandedAccess":"No"
          },
          "StartDateStruct":{
            "StartDate":"January 5, 2012"
          },
          "PrimaryCompletionDateStruct":{
            "PrimaryCompletionDate":"October 6, 2014",
            "PrimaryCompletionDateType":"Actual"
          },
          "CompletionDateStruct":{
            "CompletionDate":"October 6, 2014",
            "CompletionDateType":"Actual"
          },
          "StudyFirstSubmitDate":"January 24, 2012",
          "StudyFirstSubmitQCDate":"January 24, 2012",
          "StudyFirstPostDateStruct":{
            "StudyFirstPostDate":"January 25, 2012",
            "StudyFirstPostDateType":"Estimate"
          },
          "LastUpdateSubmitDate":"December 3, 2019",
          "LastUpdatePostDateStruct":{
            "LastUpdatePostDate":"December 4, 2019",
            "LastUpdatePostDateType":"Actual"
          }
        },
        "SponsorCollaboratorsModule":{
          "ResponsibleParty":{
            "ResponsiblePartyType":"Sponsor"
          },
          "LeadSponsor":{
            "LeadSponsorName":"National Institute on Aging (NIA)",
            "LeadSponsorClass":"NIH"
          }
        },
        "OversightModule":{
          "IsFDARegulatedDrug":"Yes"
        },
        "DescriptionModule":{
          "BriefSummary":"Background:\n\n- The endocannabinoid system is involved in different body functions and processes. It helps regulate appetite and mood, and sends signals to the nervous system. It may also be involved in how the body produces insulin during digestion. Researchers want to test two drugs that work on the endocannabinoid system: nabilone and CP-945,598. These drugs may be able to affect insulin levels in the blood. This information may suggest possible new treatments for people with diabetes.\n\nObjectives:\n\n- To study how the endocannabinoid system is involved in insulin production and action.\n\nEligibility:\n\n- Healthy men between 21 and 55 years of age.\n\nDesign:\n\nParticipants will be screened with a physical exam and medical history. They will provide blood and urine samples. They will also have imaging studies to test their brain responses, especially to food-related cues. Some participants will also have a study visit to test their insulin resistance levels.\nParticipants will have four separate study visits 6 weeks apart. They will keep a food diary before each visit. At each visit, they will have one of the following combinations of drugs:\nDouble placebo\nPlacebo and nabilone\nPlacebo and low dose of CP-945,598\nPlacebo and high dose of CP-945,598.\nParticipants will have follow-up visits 1 week after each study visit. Blood samples will be taken.",
          "DetailedDescription":"Objectives and Specific Aims:\n\nWe plan to investigate whether the endocannabinoid system is involved in the regulation of insulin secretion from Beta cells and in the modulation of insulin action in peripheral tissues in humans. We hypothesize that cannabinoid receptor 1 (CB1R) antagonist CP-945,598 will increase insulin secretion from Beta cells and improve insulin sensitivity in peripheral tissues while cannabinoid receptor (CBR) agonist nabilone will decrease insulin secretion from Beta cells and worsen insulin sensitivity in peripheral tissues. Moreover, we will investigate the brain s control over the initial phase of insulin secretion (cephalic insulin response) and the effect of central cannabinoid receptors.\n\nExperimental Design and Methods:\n\nTwenty healthy men, age 21-55, will be recruited for this study. This is a randomized, double-blind, placebo-controlled cross-over study. Each subject will serve as his own control and each person will have four different intervention visits spaced at least 6 weeks apart. During each visit, they will receive one of the following medications in random order: placebo, nabilone 2 mg, CP-945,598 15 mg, or CP-945,598 45 mg. A sequential hyperglycemic-euglycemic clamp procedure and a 3-hr oral glucose tolerance test will be used to study the effect of CP-945,598 and nabilone on insulin secretion and insulin action in healthy men. To identify brain areas involved in cephalic insulin response, a functional MRI will be used to assess brain activation in response to food images in association with frequent blood sampling.\n\nMedical Relevance and Expected Outcome:\n\nBased on our pre-clinical animal data, CB1R antagonist enhances insulin secretion and action in response to glucose while CBR agonist virtually shuts off insulin secretion and worsens insulin action in response to glucose. The application of novel, pre-clinical findings to an understanding of human biology and pathobiology is of fundamental and critical importance. This study will give us a better understanding of the regulators of insulin secretion from Beta cells and insulin sensitivity in humans, and this new understanding is of importance to finding new treatments for type 2 diabetes."
        },
        "ConditionsModule":{
          "ConditionList":{
            "Condition":[
              "Healthy"
            ]
          },
          "KeywordList":{
            "Keyword":[
              "Glucose",
              "Insulin Secretion",
              "Insulin Action",
              "Endocannabinoids",
              "Insulin",
              "Metabolism"
            ]
          }
        },
        "DesignModule":{
          "StudyType":"Interventional",
          "PhaseList":{
            "Phase":[
              "Phase 1"
            ]
          },
          "DesignInfo":{
            "DesignAllocation":"Randomized",
            "DesignInterventionModel":"Crossover Assignment",
            "DesignPrimaryPurpose":"Diagnostic",
            "DesignMaskingInfo":{
              "DesignMasking":"Double",
              "DesignWhoMaskedList":{
                "DesignWhoMasked":[
                  "Participant",
                  "Investigator"
                ]
              }
            }
          },
          "EnrollmentInfo":{
            "EnrollmentCount":"45",
            "EnrollmentType":"Actual"
          }
        },
        "ArmsInterventionsModule":{
          "InterventionList":{
            "Intervention":[
              {
                "InterventionType":"Drug",
                "InterventionName":"Nabllone",
                "InterventionDescription":"CB Agonist"
              },{
                "InterventionType":"Drug",
                "InterventionName":"CP-945,598",
                "InterventionDescription":"Cannabinoid Receptor 1 antagonist"
              },{
                "InterventionType":"Procedure",
                "InterventionName":"Hypoglycemic Clamp",
                "InterventionDescription":"Assesses beta cell response"
              },{
                "InterventionType":"Drug",
                "InterventionName":"Euglycemic-Hyperinsulinemic Clamp",
                "InterventionDescription":"Measures insulin sensitivity"
              }
            ]
          }
        },
        "OutcomesModule":{
          "PrimaryOutcomeList":{
            "PrimaryOutcome":[
              {
                "PrimaryOutcomeMeasure":"Changes in insulin sensitivity.",
                "PrimaryOutcomeTimeFrame":"6-hrs (during clamp)"
              }
            ]
          },
          "SecondaryOutcomeList":{
            "SecondaryOutcome":[
              {
                "SecondaryOutcomeMeasure":"Changes in insulin and other hormones and the brain response to pictures of food items as evidenced by a functional MRI of the brain.",
                "SecondaryOutcomeTimeFrame":"90 minutes"
              }
            ]
          }
        },
        "EligibilityModule":{
          "EligibilityCriteria":"INCLUSION CRITERIA:\n\nHealthy men only\n\n(We want to study men because the magnitude of acute insulin response for men and women is different. In addition, as women may become pregnant in the course of the study, and since this is a physiology study only, and not one related to treatments, we want to remove any confounders and lessen any chance of drop-out.)\n\nAge 21-55 (Age restriction is used to remove age as a confounding factor because Beta cells function tends to deteriorate and first phase secretion becomes less defined with age.\n\nScreening laboratory evaluations with no clinically significant abnormal results (minor deviations from normal lab results will be at the discretion of the principal investigator):\n\nfasting comprehensive metabolic panel\ncomplete blood count with differential and platelet\nthyroid function test (TSH, free T4)\nurinalysis\nurine drug screen\nBMI less than 30 (Men with BMI greater than or equal to 30 are excluded because obesity has been associated with altered beta cell function.\nHave NOT participated in another clinical trial involving any pharmacologic agents within the past 30 days\nAble to complete an inform consent\nAgree to not participate in other clinical trials within the study period (at the discretion of the study investigator)\n\nEXCLUSION CRITERIA:\n\nWomen\nFPG greater than or equal to 100 mg/dl or 2-hr OGTT greater than or equal to 140 mg/dL\nEvidence of illicit drug use\nHistory of substance abuse including marijuana within the past 6 months\nHistory of smoking any tobacco products within six months prior to screening\nAlcohol intake greater than 30 grams (drink more than 2 beers per day OR equivalent amount of alcohol)\nHistory of Human Immunodeficiency Virus (HIV) infection\nHistory of active or chronic Hepatitis B and/or C infection\nHistory of malignancy\nHistory of coronary disease\nHistory of seizures or other neurologic diseases\nHistory of psychiatric illnesses including major depressive disorder, schizophrenia, bipolar disorder\nAny lifetime history of suicide attempt\nHistory of suicidal behavior in the last year\nAny suicidal behavior during any follow-up visits\n\nHistory of any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale\n\n(C-SSRS) in the last year\n\nAny suicidal ideation of type 4 or 5 on the C-SSRS during any follow-up visits.\nPatient Health Questionnaire-9 (PHQ-9) score greater than or equal to 10 during screening visit or any follow-up study visits\nGeneralized Anxiety Disorder-7 (GAD-7) score greater than or equal to 10 during screening visit or any follow-up visits\nHistory of liver or renal diseases\nHistory of gastrointestinal or endocrine disorders\nHistory of glucocorticoid use (over one month) or other immunosuppressive agents (any)\nAny condition or non-removable device contraindicated for MRI (pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments, or history of working as a welders or metal worker)\nAny medical history that, in the opinion of the investigator(s), will make participation of the subject in the study unsafe",
          "HealthyVolunteers":"Accepts Healthy Volunteers",
          "Gender":"Male",
          "MinimumAge":"21 Years",
          "MaximumAge":"55 Years",
          "StdAgeList":{
            "StdAge":[
              "Adult"
            ]
          }
        },
        "ContactsLocationsModule":{
          "OverallOfficialList":{
            "OverallOfficial":[
              {
                "OverallOfficialName":"Josephine M Egan, M.D.",
                "OverallOfficialAffiliation":"National Institute on Aging (NIA)",
                "OverallOfficialRole":"Principal Investigator"
              }
            ]
          },
          "LocationList":{
            "Location":[
              {
                "LocationFacility":"National Institute of Aging, Clinical Research Unit",
                "LocationCity":"Baltimore",
                "LocationState":"Maryland",
                "LocationZip":"21224",
                "LocationCountry":"United States"
              }
            ]
          }
        },
        "ReferencesModule":{
          "ReferenceList":{
            "Reference":[
              {
                "ReferencePMID":"11484070",
                "ReferenceType":"background",
                "ReferenceCitation":"Pratley RE, Weyer C. The role of impaired early insulin secretion in the pathogenesis of Type II diabetes mellitus. Diabetologia. 2001 Aug;44(8):929-45. Review."
              },{
                "ReferencePMID":"15308461",
                "ReferenceType":"background",
                "ReferenceCitation":"Straub SG, Sharp GW. Hypothesis: one rate-limiting step controls the magnitude of both phases of glucose-stimulated insulin secretion. Am J Physiol Cell Physiol. 2004 Sep;287(3):C565-71. Review."
              },{
                "ReferencePMID":"8224037",
                "ReferenceType":"background",
                "ReferenceCitation":"Elahi D, Muller DC, McAloon-Dyke M, Tobin JD, Andres R. The effect of age on insulin response and glucose utilization during four hyperglycemic plateaus. Exp Gerontol. 1993 Jul-Oct;28(4-5):393-409."
              }
            ]
          }
        }
      },
      "DerivedSection":{
        "MiscInfoModule":{
          "VersionHolder":"April 22, 2020"
        },
        "InterventionBrowseModule":{
          "InterventionMeshList":{
            "InterventionMesh":[
              {
                "InterventionMeshId":"D000007004",
                "InterventionMeshTerm":"Hypoglycemic Agents"
              }
            ]
          },
          "InterventionAncestorList":{
            "InterventionAncestor":[
              {
                "InterventionAncestorId":"D000045505",
                "InterventionAncestorTerm":"Physiological Effects of Drugs"
              }
            ]
          },
          "InterventionBrowseLeafList":{
            "InterventionBrowseLeaf":[
              {
                "InterventionBrowseLeafId":"M8637",
                "InterventionBrowseLeafName":"Hypoglycemic Agents",
                "InterventionBrowseLeafAsFound":"Hypoglycemic",
                "InterventionBrowseLeafRelevance":"high"
              }
            ]
          },
          "InterventionBrowseBranchList":{
            "InterventionBrowseBranch":[
              {
                "InterventionBrowseBranchAbbrev":"All",
                "InterventionBrowseBranchName":"All Drugs and Chemicals"
              }
            ]
          }
        }
      }
    }
  }
}