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Baclofen for Treating Anxiety and Alcoholism

Sponsor
National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
Overall Status
Completed
CT.gov ID
NCT01751386
Collaborator
(none)
39
Enrollment
1
Location
2
Arms
44.5
Duration (Months)
0.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:
  • Baclofen is a drug used to control muscle stiffness in people with neurological diseases. Some studies suggest that baclofen may reduce alcohol craving and use. It helps to reduce anxiety in alcoholics, which in turn can help to reduce cravings. Researchers want to see if baclofen can be a safe and effective treatment for alcoholics who have high anxiety levels.
Objectives:
  • To see if baclofen is safe and helpful for people who have alcoholism and high anxiety levels.
Eligibility:

  • Individuals between 21 and 65 years of age who have been diagnosed with alcoholism and anxiety issues.

  • Participants must not be taking anti-anxiety medication.

Design:

  • Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Tests of alcohol dependency and anxiety levels will also be given.

  • Participants will be divided into two groups. One group will take baclofen. The other group will have a placebo.

  • About 1 week after the screening visit, participants will have a study visit. They will answer questions about their behavior and mood. They will then start to take either baclofen or a placebo. Participants will take the study drug three times a day, every day.

  • After 1 week on the study drug, participants will have an overnight stay at the National Institutes of Health. They will have blood tests and answer questions about mood and behavior. They will also have tests that involve choosing to drink alcohol and answering more questions about cravings.

  • Participants will stop taking their study drug over a 3-day period.

  • A final follow-up visit will be required 1 week after the overnight study visit. Participants will receive information about other alcohol abuse treatment programs.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Objective:

The selective GABAB receptor agonist baclofen has been identified as a possible medication able to reduce alcohol craving and intake in alcohol dependent individuals. In keeping with several preclinical studies, most of the clinical studies have demonstrated baclofen s effects in reducing alcohol craving and intake and promoting alcohol abstinence. However, one trial with alcoholics with a low severity of dependence found a robust treatment effect, but no differences between baclofen and placebo. The inconsistency of baclofen s effects on alcohol drinking among previous treatment trials suggests that different AD individuals may respond differently to baclofen. Baclofen has been demonstrated to consistently reduce anxiety in alcoholic patients, and analyses of positive vs. null findings with baclofen suggest that alcoholic patients with higher levels of anxiety at baseline may represent a sub-population particularly responsive to baclofen treatment. Therefore, this study will systematically test, for the first time, the specific role of baclofen on alcohol-related outcomes in alcoholic individuals with high anxiety levels. Furthermore, the biobehavioral mechanisms by which baclofen reduces drinking are not well characterized. A human laboratory pilot study conducted at Brown University with non-treatment seeking alcohol-dependent individuals suggests that baclofen reduces alcohol consumption both in the naturalistic environment as well as in a well-controlled lab setting (using an alcohol self-administration [ASA] paradigm) and that this could be mediated by baclofen s ability to alter alcohol-related biphasic effects. An exploratory analysis also revealed that specific genetic polymorphisms might moderate baclofen s effects, i.e. DRD4 and 5HTTLPR polymorphisms, although the sample of that pilot study was very small to allow one to draft definitive conclusions. The present project proposes investigating baclofen using a design similar to that used in the previous pilot study (thus, an already validated paradigm), thus representing not only the first study testing baclofen in alcoholic individuals with high anxiety levels, but also the first study investigating baclofen s biobehavioral mechanisms in such a population for which baclofen may hypothetically show a very robust effect.

Study population:

Non-treatment seeking alcohol-dependent males and females with high anxiety levels.

Design:

The experimental design is a between-subject randomized double-blind controlled study. The medication conditions baclofen t.i.d. or placebo represent the between subjects factor. Each participant will be randomly assigned to one of the two medication conditions and will receive eight days of the medication, followed by an alcohol laboratory session on Day 8. The alcohol laboratory session will be conducted in a bar-like room in the NIAAA Outpatient Clinic of the NIH CRC. The study will be conducted in consecutive phases which will appear contiguous to volunteers: (1) a one-week screening period; (2) an 8-day period (+ 1-5 days if needed to permit some participants flexibility in scheduling the laboratory session) during which participants will take the study medication; (3) an alcohol laboratory session, including a cue reactivity (CR) test and an alcohol self-administration (ASA) procedure on Day 8 (last day at the target dose); (4) a 3-day period during which participants will undergo a dose reduction of the study medication; (5) a 1-week follow-up (including the tapering phase).

Outcome measures:

Alcohol drinking during the ASA will be measured as the primary outcome. Secondary objectives include baclofen s effects on alcohol cue-induced responses (urge to drink, attention to cues, blood pressure, heart rate, saliva), on the subjective effects of alcohol and on anxiety levels. We will also explore the role of possible moderators of baclofen s effects, namely family history of alcoholism, early vs. later onset of alcoholism, pre-treatment anxiety levels and genetic moderators (DRD4, 5-HTTPRL). This study does not offer direct benefit to participants but is likely to yield generalizable knowledge about the possible role of baclofen in treating alcoholic individuals with high anxiety levels. This will markedly facilitate the identification of a novel pharmacotherapy, thus facilitating the development of novel alcoholism treatments.

Study Design

Study Type:
Interventional
Actual Enrollment :
39 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Other
Official Title:
A Double-Blind, Placebo-Controlled, Randomized Human Laboratory Pilot Study of Baclofen in Anxious Alcoholics
Study Start Date :
Dec 3, 2012
Actual Primary Completion Date :
Aug 17, 2016
Actual Study Completion Date :
Aug 17, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Baclofen

Baclofen 10 mg t.i.d.

Drug: Baclofen
Placebo Comparator: Placebo

Placebo t.i.d.

Other: Placebo

Outcome Measures

Primary Outcome Measures

  1. Total Amount of Alcohol Consumed During the Alcohol Self Administration (ASA) Session [2 hours]

    Amount of alcohol was measured as the number of mini-drinks each participant decided to drink (0-8 mini-drinks). The alcohol content of each mini-drink was calculated based on the participants' total body water, and was designed to raise the blood alcohol concentration by 0.015 g/dL.

Eligibility Criteria

Criteria

Ages Eligible for Study:
21 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes

  • INCLUSION CRITERIA:

  • Must be male or female between 21 and 65 years old (inclusive).

  • Participants must meet criteria for current DSM-IV-TR diagnosis of alcohol dependence, supported by the Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID).

  • Participants must have a Trait STAI > 39.

  • Participants must be in good health as confirmed by medical history, physical examination, ECG, blood/urine lab tests.

  • Females must be postmenopausal for at least one year, surgically sterile, or practicing an effective method of birth control before entry and throughout the study; have a negative urine pregnancy test at each visit. Reliable methods of birth control include oral contraceptives or Norplant ; barrier methods such as diaphragms with contraceptive jelly, cervical caps with contraceptive jelly, condoms with contraceptive foam, or intrauterine devices; a partner with a vasectomy; or abstinence from intercourse.

EXCLUSION CRITERIA:

  • Individuals expressing interest in treatment for alcoholism and/or anxiety.

  • Pregnancy or breast feeding women or not using an adequate form of birth control

  • Unable to provide a negative urine drug screen.

  • Individuals diagnosed with a current substance dependence diagnosis, other than alcohol or nicotine.

  • Meet DSM-IV Axis I criteria for a lifetime diagnosis of schizophrenia, bipolar disorder, or other psychoses.

  • An active illness within the past 6 months of Visit 1 that meet the DSM-IV criteria for a diagnosis of Major Depressive Disorder (MDD). Subjects with a history of attempted suicide will be excluded.

  • Clinically significant medical abnormalities (i.e., unstable hypertension, clinically significant ECG abnormalities, Creatinine greater than or equal to 2 mg/dL). Although baclofen has demonstrated a safe profile when administered to alcoholic individuals with liver cirrhosis, including those with Hepatitis C, this study employs the oral administration of alcohol. Therefore, individuals with clinically significant liver problems will be excluded, i.e. liver cirrhosis, AST or ALT > 5 times the upper normal limit (UNL), and individuals with Hepatitis B and C.

  • Current use of psychotropic medications that cannot be discontinued and that may have an effect on alcohol consumption (thus confounding the results of the study) or that may interact with baclofen. Specifically, contraindicated medications will include: naltrexone, acamprosate, alcohol dehydrogenase inhibitors, topiramate, gabapentin, ondansetron, benzodiazepines, beta-blockers, H2-blockers, and alpha-1 blockers.

  • Medical contraindications for use of baclofen.

  • A history of adverse reaction or hypersensitivity to baclofen.

  • Participants who have significant alcohol withdrawal symptoms, defined as a CIWA-Ar >

  • History of epilepsy or alcohol-related seizures.

Contacts and Locations

Locations

Site City State Country Postal Code
1 National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda Maryland United States 20892

Sponsors and Collaborators

  • National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

  • Principal Investigator: Lorenzo Leggio, M.D., National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
ClinicalTrials.gov Identifier:
NCT01751386
Other Study ID Numbers:
  • 130040
  • 13-AA-0040
First Posted:
Dec 18, 2012
Last Update Posted:
Sep 18, 2017
Last Verified:
Jul 17, 2017
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Keywords provided by National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Addiction
Cue-Induced Craving
Craving
Anxiety
Alcohol Consumption
Additional relevant MeSH terms:
Alcoholism
Anxiety Disorders
Alcohol Drinking
Baclofen

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Baclofen Placebo
Arm/Group Description Baclofen capsules: 15 mg/day (5 mg t.i.d.; titration phase) for 3 days, followed by 30 mg/day (10 mg t.i.d.; target dose) until the alcohol laboratory session; then, 15 mg/day (5 mg t.i.d.; taper down) for three additional days. Placebo capsules, similar to baclofen in appearance, texture, taste, and odor
Period Title: Overall Study
STARTED 20 19
COMPLETED 18 16
NOT COMPLETED 2 3

Baseline Characteristics

Arm/Group Title Baclofen Placebo Total
Arm/Group Description Baclofen capsules: 15 mg/day (5 mg t.i.d.; titration phase) for 3 days, followed by 30 mg/day (10 mg t.i.d.; target dose) until the alcohol laboratory session; then, 15 mg/day (5 mg t.i.d.; taper down) for three additional days. Placebo capsules, similar to baclofen in appearance, texture, taste, and odor Total of all reporting groups
Overall Participants 20 19 39
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
20
100%
19
100%
39
100%
>=65 years
0
0%
0
0%
0
0%
Sex: Female, Male (Count of Participants)
Female
4
20%
3
15.8%
7
17.9%
Male
16
80%
16
84.2%
32
82.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
0
0%
0
0%
Not Hispanic or Latino
20
100%
19
100%
39
100%
Unknown or Not Reported
0
0%
0
0%
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
0
0%
1
5.3%
1
2.6%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
13
65%
13
68.4%
26
66.7%
White
6
30%
4
21.1%
10
25.6%
More than one race
1
5%
1
5.3%
2
5.1%
Unknown or Not Reported
0
0%
0
0%
0
0%

Outcome Measures

1. Primary Outcome
Title Total Amount of Alcohol Consumed During the Alcohol Self Administration (ASA) Session
Description Amount of alcohol was measured as the number of mini-drinks each participant decided to drink (0-8 mini-drinks). The alcohol content of each mini-drink was calculated based on the participants' total body water, and was designed to raise the blood alcohol concentration by 0.015 g/dL.
Time Frame 2 hours

Outcome Measure Data

Analysis Population Description
The analysis included all subjects who took the medication (either baclofen or placebo) and finished the alcohol laboratory session
Arm/Group Title Baclofen Placebo
Arm/Group Description Baclofen capsules: 15 mg/day (5 mg t.i.d.; titration phase) for 3 days, followed by 30 mg/day (10 mg t.i.d.; target dose) until the alcohol laboratory session; then, 15 mg/day (5 mg t.i.d.; taper down) for three additional days. Placebo capsules, similar to baclofen in appearance, texture, taste, and odor
Measure Participants 18 16
Mean (Standard Error) [mini-drinks]
4.11
(0.66)
4.5
(0.72)

Adverse Events

Time Frame 15 days
Adverse Event Reporting Description
Arm/Group Title Baclofen Placebo
Arm/Group Description Baclofen capsules: 15 mg/day (5 mg t.i.d.; titration phase) for 3 days, followed by 30 mg/day (10 mg t.i.d.; target dose) until the alcohol laboratory session; then, 15 mg/day (5 mg t.i.d.; taper down) for three additional days. Placebo capsules, similar to baclofen in appearance, texture, taste, and odor
All Cause Mortality
Baclofen Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/20 (0%) 0/19 (0%)
Serious Adverse Events
Baclofen Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/20 (0%) 0/19 (0%)
Other (Not Including Serious) Adverse Events
Baclofen Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 9/20 (45%) 7/19 (36.8%)
Gastrointestinal disorders
Abdominal distension 0/20 (0%) 2/19 (10.5%)
Constipation 1/20 (5%) 1/19 (5.3%)
General disorders
Decreased appetite 0/20 (0%) 2/19 (10.5%)
Fatigue 0/20 (0%) 2/19 (10.5%)
Metabolism and nutrition disorders
Increased appetite 1/20 (5%) 0/19 (0%)
Musculoskeletal and connective tissue disorders
Back pain 1/20 (5%) 1/19 (5.3%)
Muscular weakness 0/20 (0%) 1/19 (5.3%)
Nervous system disorders
Dizziness 1/20 (5%) 1/19 (5.3%)
Headache 2/20 (10%) 3/19 (15.8%)
Insomnia 3/20 (15%) 2/19 (10.5%)
Memory impairment 0/20 (0%) 1/19 (5.3%)
Somnolence 4/20 (20%) 5/19 (26.3%)
Psychiatric disorders
Depression 1/20 (5%) 0/19 (0%)
Respiratory, thoracic and mediastinal disorders
Cough 0/20 (0%) 1/19 (5.3%)
Nasal congestion 0/20 (0%) 2/19 (10.5%)
Skin and subcutaneous tissue disorders
Rash 1/20 (5%) 1/19 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Lorenzo Leggio
Organization National Institute on Alcohol Abuse and Alcoholism
Phone +1 301 435 9398
Email lorenzo.leggio@mail.nih.gov
Responsible Party:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
ClinicalTrials.gov Identifier:
NCT01751386
Other Study ID Numbers:
  • 130040
  • 13-AA-0040
First Posted:
Dec 18, 2012
Last Update Posted:
Sep 18, 2017
Last Verified:
Jul 17, 2017