Role of Proinflammatory Signaling in Alcohol Craving
Condition: Alcohol Dependence; Alcohol Drinking; Stress; Alcohol-Related Disorders
MeSH terms: Alcoholism; Alcohol-Related Disorders; Alcohol Drinking
Intervention: Pioglitazone; Placebo
Intervention description: Pioglitazone is a thiazolidinedione antidiabetic. It works by lowering blood sugar by making the cells of the body more sensitive to the action of insulin.; Placebo is an inactive tablet design to look exactly like pioglitazone
Intervention MeSH terms: Pioglitazone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 16.0
Sex: All
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Alcohol; Alcohol Dependence; Alcohol Use; Nicotine Dependence; Nicotine

Summary:

      Background:

      - Drinking too much alcohol can injure cells in the body. Inflammation is the body s reaction
      to injured cells. Studies show that inflammation can cause cravings for alcohol. Researchers
      want to see if pioglitazone, a drug that decreases inflammation, can reduce alcohol craving.
      If so, it might help develop new ways to help alcoholics with craving.

      Objectives:

      - To see if pioglitazone can reduce alcohol craving.

      Eligibility:

      - Adults between 21 and 65 years of age who are alcoholic and have been drinking within the
      past month.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood samples
           will also be collected.

        -  All participants will have inpatient treatment at the National Institutes of Health
           Clinical Center for the 5 weeks of the study. They will have standard treatment for
           alcoholism during their inpatient stay.

        -  Half of the people in this study will have pioglitazone. The other half will have a
           placebo.

        -  Participants will have different studies during their stay. These studies will include
           the following:

        -  Personalized audio recordings of stressful, alcohol-related, and neutral events to
           monitor mood

        -  Imaging studies to test alcohol cravings

        -  Questionnaires about mood and alcohol cravings

        -  Lumbar puncture to collect spinal fluid

        -  Inflammation test to see if the study drug can block alcohol cravings

        -  After the end of the 5-week study, all participants will be offered follow-up outpatient
           care through the Clinical Center, or referral to outside treatment.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Diagnostic and Statistical Manual (DSM)-IV diagnosis of alcohol dependence on
                  Structured Clinical Interview for DSM Diagnosis (SCID) alcohol problems as
                  primary complaint among substance use disorders, and alcohol use within the last
                  month.

               2. Age 21 65

               3. Right handed

               4. For women:

                    1. post-menopausal or surgically sterile (tubal ligation or hysterectomy); or

                    2. if sexually active with a male partner and able to get pregnant, documented
                       agreement to use an effective form of birth control. Acceptable forms of
                       contraception for this study include: hormonal contraceptives (birth-control
                       pills, injectable hormones, vaginal-ring hormones); intrauterine device
                       (IUD); diaphragm with spermicide; condom with spermicide.

        EXCLUSION CRITERIA:

          1. Any medical illness that in the view of the investigators would compromise
             participation in research, as determined by medical history, physical examination,
             laboratory tests (see details under Screening measures below), including, but not
             limited to:

               1. Diabetes mellitus Type I or Type II

               2. Past or current diagnosis of congestive heart failure

               3. Signs and symptoms suggestive of congestive heart failure

               4. Cardiovascular disease (e.g., history of congenital heart defect, heart disease,
                  symptomatic coronary-artery disease, heart attack, clinically significant
                  arrhythmia, etc.)

               5. Cerebrovascular disease

               6. Infection, autoimmune disease, or fever of unknown origin

               7. Unexplained history of syncope

               8. History of seizures, except for febrile seizures during childhood

               9. History of head injury with loss of consciousness of more than 30 minutes or with
                  postconcussive sequelae lasting more than two days, regardless of loss of
                  consciousness

              10. Chronic renal failure as estimated by glomerular filtration rate (GFR) <60
                  milliliters per minute 1.73 per Square

              11. HIV infection

              12. Active bladder cancer, history of bladder cancer, or persistent hematuria

              13. Allergy, hypersensitivity, or intolerance to pioglitazone, other
                  thiazolidinediones, or the metabolites of any of those drugs (determined by
                  medical history)

              14. Pregnancy or breastfeeding (urine pregnancy test; self-report)

              15. Diabetes medications (e.g., sulfonylureas, metformin, insulin, etc.)

              16. Contraindicated or strongly interacting medications: Gemfibrozil (inhibitor of
                  CYP2C8) and rifampin (inducer of CYP2C8), atorvastatin, ketoconazole, nifedipine

              17. Any ongoing, or regular use of central nervous system (CNS) active medications
                  within the last week (fluoxetine: last 4 weeks), with the exception of withdrawal
                  medication, obtained according to the NIAAA clinical guidelines if needed

              18. Use of docosahexaenoic acid (DHA) dietary supplements, or consumption of oily
                  fish >3 times per week (because of effects of DHA on inflammatory parameters)

              19. History of Rhabdomyolysis

          2. Psychiatric history:

               1. Cognitive impairment severe enough to preclude informed consent or valid
                  responses on questionnaires, as established by clinical exam, in questionable
                  cases aided by a Mini Mental State Examination (with a score of <21, indicating
                  more than mild cognitive impairment, being exclusionary)

               2. Current diagnosis of schizophrenia or any other DSM-IV psychotic disorder,
                  bipolar disorder, or major depressive disorder, in each case as established by
                  clinical evaluation and SCID.

          3. Substance use disorders:

               1. Current alcohol intoxication on breathalyzer test or positive urine drug screen
                  on enrollment

               2. Current dependence on drugs other than alcohol or nicotine, as established by
                  SCID interview

          4. Inability or unwillingness to participate in an fMRI scan, including

               1. Presence of ferromagnetic objects in the body that are contraindicated for MRI of
                  the head (pacemakers or other implanted electrical devices, brain stimulators,
                  some types of dental implants, aneurysm clips, metallic prostheses, permanent
                  eyeliner, implanted delivery pump, or shrapnel fragments) or fear of enclosed
                  spaces. Eligibility will be determined by a MRI Safety Screening Questionnaire
                  and verified, if necessary, by a physician.

               2. Subjects that cannot lie comfortably flat on their back for up to 2 hours in the
                  MRI scanner.