AlcoholismPhase 2NCT01980706
Efficacy and Safety of High Dose Baclofen for Alcohol Dependence
A Phase 2 study testing Baclofen in people with Alcoholism, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
The proposed study will carefully test the hypothesis that a robust dose of baclofen (90 mg/day) has efficacy and is safe in individuals with alcohol dependence. Furthermore, the proposal will test whether an indicator of physical dependence, i.e. drinks/drinking day, predicts response to baclofen. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Alcoholism
- What is being tested?
- Baclofen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Dec 2013to 26 Oct 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women between the ages of 18 and 65 meeting Diagnostic and Statistical Manual (DSM)-IV criteria for current alcohol dependence.
- More than 14 drinks (women) or 21 drinks (men) per week including at least 2 heavy drinking days (men > 5 drinks/day; women > 4 drinks/day) per week in the 30-day period prior to screening. In addition we will recruit 50% of individuals who have a mean of ≥14 drinks/drinking day (men) or ≥10 drinks/drinking day (women) in the 30 days prior to screening.
- Ability to understand and sign written informed consent.
- Must have a 0.0 gms/dL breathalyzer reading on the day of screening and 0.0 gms/dL on the day of randomization.
- Express a desire to achieve abstinence or to greatly reduce alcohol consumption
- Must have a stable residence and be able to identify an individual who could contact participant if needed.
Who cannot join
- Clinically significant medical disease that might interfere with the evaluation of the study medication or present a safety concern (e.g., renal insufficiency, cirrhosis, unstable hypertension, diabetes mellitus, seizure disorder). Clinically significant psychiatric illness including any psychotic disorder, bipolar disorder, severe depression, or suicidal ideation.
- Other substance abuse or dependence disorder other than nicotine or alcohol or cannabis abuse.
- Occasional use of cocaine is acceptable.
- Concurrent use of any psychotropic medication including antidepressants, mood stabilizers, antipsychotics, anxiolytics, stimulants, or hypnotics with the exception of stable doses of antidepressants for one month. Concurrent use of anticonvulsants, insulin, or oral hypoglycemics.
- Prior history of adverse reaction to baclofen.
- Creatinine level > Upper Limit of Normal (ULN) or Estimated Glomerular Filtration Rate < age norm.
Show all 13Show fewer
- aspartate aminotransferase (AST), or alanine transaminase (ALT) > 5 times ULN or bilirubin > 1.5 X ULN.
- Positive urine toxicology screen with the exception of cannabis. Individuals with positive cannabis screens will be excluded only if they have a history of cannabis dependence.
- Pregnant women and women of childbearing potential who do not practice a medically acceptable form of birth control (oral or depot contraceptive, or barrier methods such as diaphragm or condom with spermicidal).
- Women who are breastfeeding.
- Individuals requiring inpatient treatment or more intense outpatient treatment for their alcohol dependence.
- Participation in any clinical trial within the past 60 days.
- Court-mandated participation in alcohol treatment or pending incarceration.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
About this study
The proposed study will carefully test the hypothesis that a robust dose of baclofen (90 mg/day) has efficacy and is safe in individuals with alcohol dependence. Furthermore, the proposal will test whether an indicator of physical dependence, i.e. drinks/drinking day, predicts response to baclofen. Additionally, the proposal will examine the anti-anxiety effects of baclofen within an alcohol dependent population and ascertain whether baseline levels of anxiety predict response to baclofen.
Read the detailed description
Alcohol dependence (AD) is a common problem with significant health consequences. Treatment of AD is evolving to include both counseling methods and medications. Several medications have been discovered, that show efficacy in AD, e.g. naltrexone, acamprosate. However, the overall effect of existing medications is modest leaving a clear need for the development of new pharmacotherapies. The gamma-aminobutyric acid (GABA)-B receptor agonist baclofen has attracted attention as a potential new medication for AD based on preclinical data and early clinical trials. Baclofen is an FDA approved medication with an excellent safety profile even for patients with liver cirrhosis-a not uncommon consequence of AD. Questions have arisen with regards to the efficacy of baclofen and whether higher doses of baclofen are safe and more effective than the prior tested dose of 30 mg/ day. There is emerging evidence that severity of dependence is positively associated with baclofen response. The main goal of the present proposal is to test the efficacy and safety of 30 mg/d and 90 mg/d of baclofen compared to placebo controlling for severity of dependence as assessed by drinks/drinking day. A primary secondary goal will examine for an anxiolytic effect of baclofen. The study proposes to enroll 120 men and women with AD in a randomized, placebo-controlled trial to include at least 60 individuals with more severe AD (≥14 drinks/drinking day for men; ≥10 drinks/drinking day for women) with randomization to baclofen or placebo balanced for this variable. Baclofen will be titrated to 10 mg t.i.d over 3 days and to 30 mg t.i.d over 12 days and maintained at that level for 12 weeks and then downtitrated for a total study time of 16 weeks. Medical Management will be provided to encourage progress towards drinking goals and to enhance retention and compliance. Drinking patterns, anxiety levels, sleep patterns, craving for alcohol, gamma-glutamyl transferase (GGT) and carbohydrate deficient transferring (CDT) will be assessed. Trough blood levels of R \& S-baclofen will be assessed in all individuals at week 4.
In summary, the present proposal is innovative and of clinical significance as it will test and compare standard and high-dose baclofen for efficacy and safety in individuals with AD. The proposal is adequately powered to test the primary hypothesis and provides good power to assess whether drinks/drinking day is predictive of baclofen response. Adequate power is also present to examine the anxiolytic effect of baclofen. Ascertaining the effects of standard and high-dose baclofen, the predictive value of heavy drinking on baclofen response and the anxiolytic effect of baclofen are important goals towards determining whether baclofen has true value for the clinical management of the patient with alcohol dependence.
- Conditions
- Alcoholism
- Being tested
- Baclofen, Placebo
- Keywords
- Baclofen, Alcohol Dependence
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BaclofenDrug
Also called Lioresal
Baclofen is a GABA-B agonist
PlaceboDrug
Also called Sugar pill
Pill containing no pharmacologically active substance.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants will take placebo for 16 weeks, 3 times per day. Placebo will be given in blister packs. Receives: Drug: Placebo |
| 30 Mg Baclofen | Active comparator | Participants will take baclofen/placebo for 16 weeks, 3 times per day. Baclofen will be given in blister packs. The 30 mg/d arm will reach 30 mg/d at day 3 and titrate down starting at day 101. Receives: Drug: Baclofen |
| 90 mg Baclofen | Active comparator | Participants will take baclofen/placebo for 16 weeks, 3 times per day. Baclofen will be given in blister packs. The 90 mg/d arm will reach 90 mg/d at day 12 and titrate down starting at day 95. Receives: Drug: Baclofen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Percentage of Heavy Drinking Days
The frequency of heavy drinking days (5 or more drinks for a man and 4 or more drinks for a woman) as percentage during the treatment phase.
Measured: Every 1-2 weeks up to 16 weeks of active trial
Mean Percentage of Abstinent Drinking Days
Percent of abstinent days over the course of the trial.
Measured: Every 1-2 weeks up to 16 weeks of active trial
Secondary outcomes (3)
Mean Spielberger State-Trait Anxiety Inventory Score [State]
The Spielberger State and Trait Anxiety Inventory (STAI) is a validated self-reporting instrument used to assess anxiety in adults.The inventory consists of state anxiety, which evaluates how the subject feels currently (transient anxiety). The State scale consists of 20 questions, each question rated 1-4, and a higher score indicates greater anxiety. Total score ranges from 20 (no anxiety) to 80 (maximum anxiety). The scores are averaged over the trial.
Measured: Every 1-2 weeks up to 16 weeks of active trial
Mean Penn Alcohol Craving Scale Score
Penn Alcohol Craving Scale (PACS) is a five-item self administered instrument for assessing craving, frequency, intensity, and duration of thoughts about drinking as well as the ability to resist drinking. Scores range from a minimum of zero to a maximum of 30. Lower scores are associated with lower level of craving for alcohol. Scores are averaged over the trial.
Measured: Every 1-2 weeks up to 16 weeks of active trial
Carbohydrate-deficient Transferrin
Lab test assessing history of heavy drinking with greater specificity than GGT. Higher levels are indicative of greater levels of drinking.
Measured: End of trial, generally 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2013 (estimated)
- Study start12 Dec 2013
- Primary completion26 Oct 2017
- Study completion26 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AlcoholismStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor
- Investigators
- James C Garbutt, MD, Principal investigator, University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01980706
- Sponsor's protocol ID
- 12-1743
- Other IDs
- 4R01AA020824-04
- Status last verified
- Oct 2018
- First submitted
- 28 Oct 2013
- Last updated
- 12 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of High Dose Baclofen for Alcohol Dependence
- ClinicalTrials.gov ID
- NCT01980706
- Acronym / sponsor ID
- 12-1743
- Conditions
- Alcoholism
- Keywords
- Baclofen, Alcohol Dependence
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 12 Dec 2013 (actual)
- Primary completion
- 26 Oct 2017 (actual)
- Study completion
- 26 Oct 2017 (actual)
- First posted
- 11 Nov 2013 (estimated)
- Results
- Posted 8 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study will carefully test the hypothesis that a robust dose of baclofen (90 mg/day) has efficacy and is safe in individuals with alcohol dependence. Furthermore, the proposal will test whether an indicator of physical dependence, i.e. drinks/drinking day, predicts response to baclofen. Additionally, the proposal will examine the anti-anxiety effects of baclofen within an alcohol dependent population and ascertain whether baseline levels of anxiety predict response to baclofen.
Detailed description
Alcohol dependence (AD) is a common problem with significant health consequences. Treatment of AD is evolving to include both counseling methods and medications. Several medications have been discovered, that show efficacy in AD, e.g. naltrexone, acamprosate. However, the overall effect of existing medications is modest leaving a clear need for the development of new pharmacotherapies. The gamma-aminobutyric acid (GABA)-B receptor agonist baclofen has attracted attention as a potential new medication for AD based on preclinical data and early clinical trials. Baclofen is an FDA approved medication with an excellent safety profile even for patients with liver cirrhosis-a not uncommon consequence of AD. Questions have arisen with regards to the efficacy of baclofen and whether higher doses of baclofen are safe and more effective than the prior tested dose of 30 mg/ day. There is emerging evidence that severity of dependence is positively associated with baclofen response. The main goal of the present proposal is to test the efficacy and safety of 30 mg/d and 90 mg/d of baclofen compared to placebo controlling for severity of dependence as assessed by drinks/drinking day. A primary secondary goal will examine for an anxiolytic effect of baclofen. The study proposes to enroll 120 men and women with AD in a randomized, placebo-controlled trial to include at least 60 individuals with more severe AD (≥14 drinks/drinking day for men; ≥10 drinks/drinking day for women) with randomization to baclofen or placebo balanced for this variable. Baclofen will be titrated to 10 mg t.i.d over 3 days and to 30 mg t.i.d over 12 days and maintained at that level for 12 weeks and then downtitrated for a total study time of 16 weeks. Medical Management will be provided to encourage progress towards drinking goals and to enhance retention and compliance. Drinking patterns, anxiety levels, sleep patterns, craving for alcohol, gamma-glutamyl transferase (GGT) and carbohydrate deficient transferring (CDT) will be assessed. Trough blood levels of R \& S-baclofen will be assessed in all individuals at week 4.
In summary, the present proposal is innovative and of clinical significance as it will test and compare standard and high-dose baclofen for efficacy and safety in individuals with AD. The proposal is adequately powered to test the primary hypothesis and provides good power to assess whether drinks/drinking day is predictive of baclofen response. Adequate power is also present to examine the anxiolytic effect of baclofen. Ascertaining the effects of standard and high-dose baclofen, the predictive value of heavy drinking on baclofen response and the anxiolytic effect of baclofen are important goals towards determining whether baclofen has true value for the clinical management of the patient with alcohol dependence.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants will take placebo for 16 weeks, 3 times per day. Placebo will be given in blister packs. |
| 30 Mg Baclofen | Active comparator | Drug: BaclofenParticipants will take baclofen/placebo for 16 weeks, 3 times per day. Baclofen will be given in blister packs. The 30 mg/d arm will reach 30 mg/d at day 3 and titrate down starting at day 101. |
| 90 mg Baclofen | Active comparator | Drug: BaclofenParticipants will take baclofen/placebo for 16 weeks, 3 times per day. Baclofen will be given in blister packs. The 90 mg/d arm will reach 90 mg/d at day 12 and titrate down starting at day 95. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women between the ages of 18 and 65 meeting Diagnostic and Statistical Manual (DSM)-IV criteria for current alcohol dependence.
- More than 14 drinks (women) or 21 drinks (men) per week including at least 2 heavy drinking days (men > 5 drinks/day; women > 4 drinks/day) per week in the 30-day period prior to screening. In addition we will recruit 50% of individuals who have a mean of ≥14 drinks/drinking day (men) or ≥10 drinks/drinking day (women) in the 30 days prior to screening.
- Ability to understand and sign written informed consent.
- Must have a 0.0 gms/dL breathalyzer reading on the day of screening and 0.0 gms/dL on the day of randomization.
- Express a desire to achieve abstinence or to greatly reduce alcohol consumption
Key exclusion criteria (13 listed)
- Clinically significant medical disease that might interfere with the evaluation of the study medication or present a safety concern (e.g., renal insufficiency, cirrhosis, unstable hypertension, diabetes mellitus, seizure disorder). Clinically significant psychiatric illness including any psychotic disorder, bipolar disorder, severe depression, or suicidal ideation.
- Other substance abuse or dependence disorder other than nicotine or alcohol or cannabis abuse.
- Occasional use of cocaine is acceptable.
- Concurrent use of any psychotropic medication including antidepressants, mood stabilizers, antipsychotics, anxiolytics, stimulants, or hypnotics with the exception of stable doses of antidepressants for one month. Concurrent use of anticonvulsants, insulin, or oral hypoglycemics.
- Prior history of adverse reaction to baclofen.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BaclofenAlso: LioresalBaclofen is a GABA-B agonist | Drug | 30 Mg Baclofen, 90 mg Baclofen |
| PlaceboAlso: Sugar pillPill containing no pharmacologically active substance. | Drug | Placebo |
Primary outcome
Mean Percentage of Heavy Drinking Days
Time frame: Every 1-2 weeks up to 16 weeks of active trial
The frequency of heavy drinking days (5 or more drinks for a man and 4 or more drinks for a woman) as percentage during the treatment phase.
Mean Percentage of Abstinent Drinking Days
Time frame: Every 1-2 weeks up to 16 weeks of active trial
Percent of abstinent days over the course of the trial.
3 secondary outcomes
Mean Spielberger State-Trait Anxiety Inventory Score [State]
Time frame: Every 1-2 weeks up to 16 weeks of active trial
Mean Penn Alcohol Craving Scale Score
Time frame: Every 1-2 weeks up to 16 weeks of active trial
Carbohydrate-deficient Transferrin
Time frame: End of trial, generally 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James C Garbutt, MD principal investigator
University of North Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Baclofen in people with Alcoholism, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Percentage of Heavy Drinking Days (time frame: Every 1-2 weeks up to 16 weeks of active trial). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2019.