NCT01631630

Brief 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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started May 2012

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2012

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

June 27, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 29, 2012

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2015

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

December 15, 2016

Completed
Last Updated

March 9, 2017

Status Verified

January 1, 2017

Enrollment Period

3.3 years

First QC Date

June 27, 2012

Results QC Date

October 21, 2016

Last Update Submit

January 27, 2017

Conditions

Alcohol DependenceAlcohol DrinkingStressAlcohol-Related Disorders

Keywords

AlcoholAlcohol DependenceAlcohol UseNicotine DependenceNicotine

Outcome Measures

Primary Outcomes (23)

  • Alcohol Craving in Response to the Alcohol Cue Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    15 minutes prior to the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Alcohol Cue Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    5 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Alcohol Cue Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    15 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Alcohol Cue Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    30 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Alcohol Cue Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    45 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Alcohol Cue Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    60 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Alcohol Cue Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    75 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Alcohol Cue Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    90 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Lipopolysaccharide Challenge

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    15 minutes prior to the subject receiving an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period

  • Alcohol Craving in Response to the Lipopolysaccharide Challenge

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    1 hour after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period

  • Alcohol Craving in Response to the Lipopolysaccharide Challenge

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    2 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period

  • Alcohol Craving in Response to the Lipopolysaccharide Challenge

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    3 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period

  • Alcohol Craving in Response to the Lipopolysaccharide Challenge

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    4 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period

  • Alcohol Craving in Response to the Lipopolysaccharide Challenge

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    5 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period

  • Alcohol Craving in Response to the Lipopolysaccharide Challenge

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    6 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period

  • Alcohol Craving in Response to the Stress Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    15 minutes prior to the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Stress Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    15 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Stress Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    5 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Stress Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    30 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Stress Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    45 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Stress Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    60 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Stress Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    75 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

  • Alcohol Craving in Response to the Stress Script

    Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

    90 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

Secondary Outcomes (30)

  • Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period

    Day 1 of the treatment period

  • Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period

    Day 3 of the treatment period

  • Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period

    Day 7 of the treatment period

  • Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period

    Day 10 of the treatment period

  • Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period

    Day 14 of the treatment period

  • +25 more secondary outcomes

Study Arms (2)

Pioglitazone

EXPERIMENTAL

Subjects received pioglitazone, 15mg/day for 3 days; 30mg day for 3 days; 45mg/day thereafter, for a minimum total of 13 days

Drug: Pioglitazone

Placebo

PLACEBO COMPARATOR

Subjects received placebo on a similar dosing schedule, for a minimum total of 13 days

Drug: Placebo

Interventions

PioglitazoneDRUG

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.

Also known as: Actos
Pioglitazone
PlaceboDRUG

Placebo is an inactive tablet design to look exactly like pioglitazone

Also known as: Sugar Pill
Placebo

Eligibility Criteria

Age21 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • Age 21 65
  • Right handed
  • For women:
  • post-menopausal or surgically sterile (tubal ligation or hysterectomy); or
  • 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.

You may not qualify if:

  • 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:
  • Diabetes mellitus Type I or Type II
  • Past or current diagnosis of congestive heart failure
  • Signs and symptoms suggestive of congestive heart failure
  • Cardiovascular disease (e.g., history of congenital heart defect, heart disease, symptomatic coronary-artery disease, heart attack, clinically significant arrhythmia, etc.)
  • Cerebrovascular disease
  • Infection, autoimmune disease, or fever of unknown origin
  • Unexplained history of syncope
  • History of seizures, except for febrile seizures during childhood
  • 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
  • Chronic renal failure as estimated by glomerular filtration rate (GFR) \<60 milliliters per minute 1.73 per Square
  • HIV infection
  • Active bladder cancer, history of bladder cancer, or persistent hematuria
  • Allergy, hypersensitivity, or intolerance to pioglitazone, other thiazolidinediones, or the metabolites of any of those drugs (determined by medical history)
  • Pregnancy or breastfeeding (urine pregnancy test; self-report)
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

  • Capuron L, Miller AH. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther. 2011 May;130(2):226-38. doi: 10.1016/j.pharmthera.2011.01.014. Epub 2011 Feb 17.

    PMID: 21334376BACKGROUND

  • Crews FT, Zou J, Qin L. Induction of innate immune genes in brain create the neurobiology of addiction. Brain Behav Immun. 2011 Jun;25 Suppl 1(Suppl 1):S4-S12. doi: 10.1016/j.bbi.2011.03.003. Epub 2011 Mar 21.

    PMID: 21402143BACKGROUND

  • Dantzer R, Kelley KW. Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun. 2007 Feb;21(2):153-60. doi: 10.1016/j.bbi.2006.09.006. Epub 2006 Nov 7.

    PMID: 17088043BACKGROUND

  • Schwandt ML, Diazgranados N, Umhau JC, Kwako LE, George DT, Heilig M. PPARgamma activation by pioglitazone does not suppress cravings for alcohol, and is associated with a risk of myopathy in treatment seeking alcohol dependent patients: a randomized controlled proof of principle study. Psychopharmacology (Berl). 2020 Aug;237(8):2367-2380. doi: 10.1007/s00213-020-05540-w. Epub 2020 May 22.

    PMID: 32445052DERIVED

Related Links

MeSH Terms

Conditions

AlcoholismAlcohol DrinkingAlcohol-Related DisordersTobacco Use Disorder

Interventions

PioglitazoneSugars

Condition Hierarchy (Ancestors)

Substance-Related DisordersChemically-Induced DisordersMental DisordersDrinking BehaviorBehavior

Intervention Hierarchy (Ancestors)

ThiazolidinedionesThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsCarbohydrates

Limitations and Caveats

This study was terminated early, so the number of subjects analyzed is small.

Results Point of Contact

Title
Diazgranados, Nancy
Organization
National Institute on Alcohol Abuse and Alcoholism
nancy.diazgranados@nih.gov
+1 301 435 9386

Study Officials

  • Nancy Diazgranados, M.D.

    National Institute on Alcohol Abuse and Alcoholism (NIAAA)

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 27, 2012

First Posted

June 29, 2012

Study Start

May 1, 2012

Primary Completion

September 1, 2015

Study Completion

September 1, 2015

Last Updated

March 9, 2017

Results First Posted

December 15, 2016

Record last verified: 2017-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)