Efficacy and Safety of High Dose Baclofen for Alcohol Dependence
Study Details
Study Description
Brief 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. 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Participants will take placebo for 16 weeks, 3 times per day. Placebo will be given in blister packs. |
Drug: Placebo
Pill containing no pharmacologically active substance.
Other Names:
|
| Active Comparator: 30 Mg Baclofen 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. |
Drug: Baclofen
Baclofen is a GABA-B agonist
Other Names:
|
| Active Comparator: 90 mg Baclofen 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. |
Drug: Baclofen
Baclofen is a GABA-B agonist
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Mean Percentage of Heavy Drinking Days [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 [Every 1-2 weeks up to 16 weeks of active trial]
Percent of abstinent days over the course of the trial.
Secondary Outcome Measures
- Mean Spielberger State-Trait Anxiety Inventory Score [State] [Every 1-2 weeks up to 16 weeks of active trial]
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.
- Mean Penn Alcohol Craving Scale Score [Every 1-2 weeks up to 16 weeks of active trial]
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.
- Carbohydrate-deficient Transferrin [End of trial, generally 16 weeks]
Lab test assessing history of heavy drinking with greater specificity than GGT. Higher levels are indicative of greater levels of drinking.
Other Outcome Measures
- Self-reported Sedation on at Least One Occasion by a Participant [Every 1-2 weeks up to 16 weeks of active trial]
Any reporting of feeling sedated/sleepy/drowsy
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
Exclusion Criteria:
-
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.
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
Sponsors and Collaborators
- University of North Carolina, Chapel Hill
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
- Principal Investigator: James C Garbutt, MD, University of North Carolina
Study Documents (Full-Text)
More Information
Publications
None provided.- 12-1743
- 4R01AA020824-04
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | 30 Mg Baclofen | 90 mg Baclofen |
|---|---|---|---|
| Arm/Group Description | Participants will take placebo for 16 weeks, 3 times per day. Placebo will be given in blister packs. Placebo: Pill containing no pharmacologically active substance. | 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. Baclofen: Baclofen is a gamma-aminobutyric acid (GABA)-B receptor agonist | 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. Baclofen: Baclofen is a GABA-B agonist |
| Period Title: Overall Study | |||
| STARTED | 40 | 43 | 37 |
| COMPLETED | 23 | 26 | 24 |
| NOT COMPLETED | 17 | 17 | 13 |
Baseline Characteristics
| Arm/Group Title | Placebo | 30 Mg Baclofen | 90 mg Baclofen | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants will take placebo for 16 weeks, 3 times per day. Placebo will be given in blister packs. Placebo: Pill containing no pharmacologically active substance. | 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. Baclofen: Baclofen is a GABA-B agonist | 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. Baclofen: Baclofen is a GABA-B agonist | Total of all reporting groups |
| Overall Participants | 40 | 43 | 37 | 120 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
47.1
(9.6)
|
46.1
(10.4)
|
44.8
(10.3)
|
46.0
(10.1)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
20
50%
|
21
48.8%
|
17
45.9%
|
58
48.3%
|
| Male |
20
50%
|
22
51.2%
|
20
54.1%
|
62
51.7%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
1
2.5%
|
0
0%
|
0
0%
|
1
0.8%
|
| Asian |
0
0%
|
1
2.3%
|
1
2.7%
|
2
1.7%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
3
7.5%
|
5
11.6%
|
6
16.2%
|
14
11.7%
|
| White |
36
90%
|
36
83.7%
|
30
81.1%
|
102
85%
|
| More than one race |
0
0%
|
1
2.3%
|
0
0%
|
1
0.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | ||||
| United States |
40
100%
|
43
100%
|
37
100%
|
120
100%
|
| Baseline Percentage of Heavy Drinking Days (percentage of heavy drinking days) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [percentage of heavy drinking days] |
79
(21)
|
73
(23)
|
70
(26)
|
74
(23)
|
| Baseline Percentage of Abstinent Days (Percentage of Abstinent Days) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Percentage of Abstinent Days] |
13
(17)
|
17
(19)
|
18
(20)
|
16
(19)
|
| Baseline Drinks/drinking day (drinks per drinking day) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [drinks per drinking day] |
9.3
(3.9)
|
10.7
(7.7)
|
10.0
(4.2)
|
10.0
(5.6)
|
| Goal of Abstinence (Count of Participants) | ||||
| Count of Participants [Participants] |
16
40%
|
24
55.8%
|
12
32.4%
|
52
43.3%
|
| Craving for Alcohol (units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [units on a scale] |
14.5
(6.8)
|
15.5
(7.2)
|
15.3
(6.1)
|
15.1
(6.7)
|
| Carbohydrate Deficient Transferrin (CDT) (% CDT) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [% CDT] |
2.31
(1.95)
|
1.72
(0.63)
|
2.22
(1.46)
|
2.07
(1.46)
|
| Speilberger State Anxiety (units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [units on a scale] |
35.0
(10.5)
|
36.3
(12.4)
|
35.7
(9.7)
|
35.7
(10.9)
|
Outcome Measures
| Title | Mean Percentage of Heavy Drinking Days |
|---|---|
| Description | 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. |
| Time Frame | Every 1-2 weeks up to 16 weeks of active trial |
Outcome Measure Data
| Analysis Population Description |
|---|
| Post-randomization data were unavailable for 2 participants. |
| Arm/Group Title | Placebo | 30 Mg Baclofen | 90 mg Baclofen |
|---|---|---|---|
| Arm/Group Description | Participants will take placebo for 16 weeks, 3 times per day. Placebo will be given in blister packs. Placebo: Pill containing no pharmacologically active substance. | 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. Baclofen: Baclofen is a GABA-B agonist | 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. Baclofen: Baclofen is a GABA-B agonist |
| Measure Participants | 40 | 42 | 36 |
| Least Squares Mean (Standard Error) [percentage of heavy drinking days] |
39
(4)
|
42
(4)
|
28
(4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 Mg Baclofen, 90 mg Baclofen |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.018 |
| Comments | Threshold for significance is <.05 | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 4.16 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Overall, treatment effect F value testing under the null hypothesis the equality of the average outcome over the three groups. | |
| Title | Mean Percentage of Abstinent Drinking Days |
|---|---|
| Description | Percent of abstinent days over the course of the trial. |
| Time Frame | Every 1-2 weeks up to 16 weeks of active trial |
Outcome Measure Data
| Analysis Population Description |
|---|
| Post-randomization data were unavailable for 2 participants. |
| Arm/Group Title | Placebo | 30 Mg Baclofen | 90 mg Baclofen |
|---|---|---|---|
| Arm/Group Description | Participants will take placebo for 16 weeks, 3 times per day. Placebo will be given in blister packs. Placebo: Pill containing no pharmacologically active substance. | 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. Baclofen: Baclofen is a GABA-B agonist | 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. Baclofen: Baclofen is a GABA-B agonist |
| Measure Participants | 40 | 42 | 36 |
| Least Squares Mean (Standard Error) [percentage of days] |
47
(4)
|
48
(4)
|
59
(4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 Mg Baclofen, 90 mg Baclofen |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.028 |
| Comments | Threshold for significance is <.05 | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 3.68 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Overall, treatment effect F value testing under the null hypothesis the equality of the average outcome over the three groups. | |
| Title | Mean Spielberger State-Trait Anxiety Inventory Score [State] |
|---|---|
| Description | 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. |
| Time Frame | Every 1-2 weeks up to 16 weeks of active trial |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | 30 Mg Baclofen | 90 mg Baclofen |
|---|---|---|---|
| Arm/Group Description | Participants will take placebo for 16 weeks, 3 times per day. Placebo will be given in blister packs. Placebo: Pill containing no pharmacologically active substance. | 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. Baclofen: Baclofen is a GABA-B agonist | 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. Baclofen: Baclofen is a GABA-B agonist |
| Measure Participants | 40 | 43 | 37 |
| Least Squares Mean (Standard Error) [units on a scale] |
35.2
(1.16)
|
33.8
(1.12)
|
33.6
(1.18)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 Mg Baclofen, 90 mg Baclofen |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.52 |
| Comments | Threshold for significance is <.05 | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.65 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Overall, treatment effect F value testing under the null hypothesis the equality of the average outcome over the three groups. | |
| Title | Mean Penn Alcohol Craving Scale Score |
|---|---|
| Description | 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. |
| Time Frame | Every 1-2 weeks up to 16 weeks of active trial |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | 30 Mg Baclofen | 90 mg Baclofen |
|---|---|---|---|
| Arm/Group Description | Participants will take placebo for 16 weeks, 3 times per day. Placebo will be given in blister packs. Placebo: Pill containing no pharmacologically active substance. | 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. Baclofen: Baclofen is a GABA-B agonist | 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. Baclofen: Baclofen is a GABA-B agonist |
| Measure Participants | 40 | 43 | 37 |
| Least Squares Mean (Standard Error) [units on a scale] |
10.1
(0.91)
|
10.8
(0.88)
|
9.4
(0.92)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 Mg Baclofen, 90 mg Baclofen |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.43 |
| Comments | Threshold for significance is <.05 | |
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.84 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Overall, treatment effect F value testing under the null hypothesis the equality of the average outcome over the three groups. | |
| Title | Carbohydrate-deficient Transferrin |
|---|---|
| Description | Lab test assessing history of heavy drinking with greater specificity than GGT. Higher levels are indicative of greater levels of drinking. |
| Time Frame | End of trial, generally 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Post-randomization CDT was not collected for all participants. |
| Arm/Group Title | Placebo | 30 Mg Baclofen | 90 mg Baclofen |
|---|---|---|---|
| Arm/Group Description | Participants will take placebo for 16 weeks, 3 times per day. Placebo will be given in blister packs. Placebo: Pill containing no pharmacologically active substance. | 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. Baclofen: Baclofen is a GABA-B agonist | 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. Baclofen: Baclofen is a GABA-B agonist |
| Measure Participants | 18 | 20 | 17 |
| Least Squares Mean (Standard Error) [% CDT] |
1.81
(.26)
|
2.19
(.26)
|
1.96
(.28)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 Mg Baclofen, 90 mg Baclofen |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.60 |
| Comments | Threshold for significance is <.05 | |
| Method | ANCOVA | |
| Comments | Adjusted for baseline | |
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.52 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Estimated parameter is the overall treatment main effect F statistic from the fitted ANCOVA model assessing the null hypothesis of equal values across the three groups | |
| Title | Self-reported Sedation on at Least One Occasion by a Participant |
|---|---|
| Description | Any reporting of feeling sedated/sleepy/drowsy |
| Time Frame | Every 1-2 weeks up to 16 weeks of active trial |
Outcome Measure Data
| Analysis Population Description |
|---|
| Post-randomization data were unavailable for 2 participants. |
| Arm/Group Title | Placebo | 30 Mg Baclofen | 90 mg Baclofen |
|---|---|---|---|
| Arm/Group Description | Participants will take placebo for 16 weeks, 3 times per day. Placebo will be given in blister packs. Placebo: Pill containing no pharmacologically active substance. | 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. Baclofen: Baclofen is a GABA-B agonist | 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. Baclofen: Baclofen is a GABA-B agonist |
| Measure Participants | 40 | 42 | 36 |
| Count of Participants [Participants] |
14
35%
|
25
58.1%
|
20
54.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 30 Mg Baclofen, 90 mg Baclofen |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.07 |
| Comments | Threshold for significance is <.05 | |
| Method | Fisher Exact | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Table probability for Fisher's Exact |
| Estimated Value | .002 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Throughout treatment and for 4 weeks after treatment ended. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Placebo | 30 Mg Baclofen | 90 mg Baclofen | |||
| Arm/Group Description | Participants will take placebo for 16 weeks, 3 times per day. Placebo will be given in blister packs. Placebo: Pill containing no pharmacologically active substance. | 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. Baclofen: Baclofen is a GABA-B agonist | 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. Baclofen: Baclofen is a GABA-B agonist | |||
All Cause Mortality |
||||||
| Placebo | 30 Mg Baclofen | 90 mg Baclofen | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/40 (0%) | 0/43 (0%) | 0/37 (0%) | |||
Serious Adverse Events |
||||||
| Placebo | 30 Mg Baclofen | 90 mg Baclofen | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/40 (0%) | 0/43 (0%) | 1/37 (2.7%) | |||
| Nervous system disorders | ||||||
| Drowsiness | 0/40 (0%) | 0 | 0/43 (0%) | 0 | 1/37 (2.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Placebo | 30 Mg Baclofen | 90 mg Baclofen | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/40 (40%) | 28/43 (65.1%) | 21/37 (56.8%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 4/40 (10%) | 5/43 (11.6%) | 4/37 (10.8%) | |||
| Constipation | 3/40 (7.5%) | 4/43 (9.3%) | 2/37 (5.4%) | |||
| General disorders | ||||||
| Fatigue/low energy | 2/40 (5%) | 5/43 (11.6%) | 2/37 (5.4%) | |||
| Headache | 3/40 (7.5%) | 5/43 (11.6%) | 4/37 (10.8%) | |||
| Nervous system disorders | ||||||
| Sedation | 14/40 (35%) | 25/43 (58.1%) | 20/37 (54.1%) | |||
| Dizziness | 5/40 (12.5%) | 12/43 (27.9%) | 8/37 (21.6%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Itchiness/rash | 4/40 (10%) | 8/43 (18.6%) | 0/37 (0%) | |||
Limitations/Caveats
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 | James C Garbutt, MD |
|---|---|
| Organization | University of North Carolina at Chapel Hill |
| Phone | 984-974-2201 |
| jc_garbutt@med.unc.edu |
- 12-1743
- 4R01AA020824-04