Trial Outcomes & Findings for Treatment of Alcohol Dependence and Comorbid Bipolar Disorder (NCT NCT01015586)

Results Overview

Percentage of days in trial without consumption of alcoholic beverages per participant self-report; minimum = 0, maximum = 100; higher numbers indicate better outcome. Percent days abstinent was calculated as: (number of days abstinent per self-report / total number of days in trial)\*100.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

43 participants

Primary outcome timeframe

12 weeks

Results posted on

2019-01-09

Participant Flow

Participant milestones

Participant milestones
Measure	Lamotrigine Add-on lamotrigine plus pre-existing mood stabilizing medication regimen. Active fixed-dose drug titration from 25-200 mg/day over first six weeks, 200 mg/day fixed-dose maintenance for second six weeks Lamotrigine: Six week titration from 25 mg/day to 200 mg/day, then 200 mg/day maintenance for additional six weeks	Placebo Add-on placebo plus pre-existing mood stabilization regimen for 12 weeks Placebo: Placebo once daily for 12 weeks
Overall Study STARTED	21	22
Overall Study COMPLETED	14	11
Overall Study NOT COMPLETED	7	11

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Treatment of Alcohol Dependence and Comorbid Bipolar Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lamotrigine n=21 Participants Add-on lamotrigine plus pre-existing mood stabilizing medication regimen. Active fixed-dose drug titration from 25-200 mg/day over first six weeks, 200 mg/day fixed-dose maintenance for second six weeks Lamotrigine: Six week titration from 25 mg/day to 200 mg/day, then 200 mg/day maintenance for additional six weeks	Placebo n=22 Participants Add-on placebo plus pre-existing mood stabilization regimen for 12 weeks Placebo: Placebo once daily for 12 weeks	Total n=43 Participants Total of all reporting groups
Age, Continuous	44.48 years STANDARD_DEVIATION 11.46 • n=99 Participants	44.14 years STANDARD_DEVIATION 10.13 • n=107 Participants	44.30 years STANDARD_DEVIATION 10.67 • n=206 Participants
Sex: Female, Male Female	6 Participants n=99 Participants	7 Participants n=107 Participants	13 Participants n=206 Participants
Sex: Female, Male Male	15 Participants n=99 Participants	15 Participants n=107 Participants	30 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	5 Participants n=99 Participants	2 Participants n=107 Participants	7 Participants n=206 Participants
Race (NIH/OMB) White	16 Participants n=99 Participants	20 Participants n=107 Participants	36 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	21 participants n=99 Participants	22 participants n=107 Participants	43 participants n=206 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Analysis is of modified intention to treat (ITT) sample comprised of all randomized subjects who returned for at least one study visit after randomization.

Percentage of days in trial without consumption of alcoholic beverages per participant self-report; minimum = 0, maximum = 100; higher numbers indicate better outcome. Percent days abstinent was calculated as: (number of days abstinent per self-report / total number of days in trial)\*100.

Outcome measures

Outcome measures
Measure	Lamotrigine n=20 Participants Add-on lamotrigine plus pre-existing mood stabilizing medication regimen. Active fixed-dose drug titration from 25-200 mg/day over first six weeks, 200 mg/day fixed-dose maintenance for second six weeks Lamotrigine: Six week titration from 25 mg/day to 200 mg/day, then 200 mg/day maintenance for additional six weeks	Placebo n=17 Participants Add-on placebo plus pre-existing mood stabilization regimen for 12 weeks Placebo: Placebo once daily for 12 weeks
Percent Days Abstinent From Alcohol	78.7 Percentage of days abstinent Standard Deviation 30.0	80.1 Percentage of days abstinent Standard Deviation 28.4

SECONDARY outcome

Timeframe: 12 weeks

Population: Analysis is of modified intention to treat (mITT) sample comprised of all randomized subjects who returned for at least one study visit after randomization (total mITT sample n=37).

Percentage of days in trial that were heavy drinking days (5 or more drinks/day for men, 4 or more drinks/day for women); minimum = 0, maximum = 100; lower numbers indicate better outcome. Percent heavy drinking days was calculated as: (number of days of heavy drinking per self-report / total number of days in trial)\*100.

Outcome measures

Outcome measures
Measure	Lamotrigine n=20 Participants Add-on lamotrigine plus pre-existing mood stabilizing medication regimen. Active fixed-dose drug titration from 25-200 mg/day over first six weeks, 200 mg/day fixed-dose maintenance for second six weeks Lamotrigine: Six week titration from 25 mg/day to 200 mg/day, then 200 mg/day maintenance for additional six weeks	Placebo n=17 Participants Add-on placebo plus pre-existing mood stabilization regimen for 12 weeks Placebo: Placebo once daily for 12 weeks
Percent Heavy Drinking Days	8.1 Percentage of heavy drinking days Standard Deviation 12.8	11.6 Percentage of heavy drinking days Standard Deviation 21.1

SECONDARY outcome

Timeframe: 12 weeks after randomization

Population: The sample analyzed is limited to study completers (total n=25) due to this measure being obtained at study endpoint.

Serum levels of biomarkers of alcohol use: carbohydrate-deficient transferrin (CDT) at study endpoint in study completers

Outcome measures

Outcome measures
Measure	Lamotrigine n=13 Participants Add-on lamotrigine plus pre-existing mood stabilizing medication regimen. Active fixed-dose drug titration from 25-200 mg/day over first six weeks, 200 mg/day fixed-dose maintenance for second six weeks Lamotrigine: Six week titration from 25 mg/day to 200 mg/day, then 200 mg/day maintenance for additional six weeks	Placebo n=12 Participants Add-on placebo plus pre-existing mood stabilization regimen for 12 weeks Placebo: Placebo once daily for 12 weeks
Biomarkers of Alcohol Use: Carbohydrate-deficient Transferrin (CDT)	1.41 "percent CDT" Standard Deviation .48	1.26 "percent CDT" Standard Deviation .18

SECONDARY outcome

Timeframe: 12 weeks after randomization

Population: Sample in this analysis is limited to study completers only (total n=25) because this measure was obtained at study endpoint.

Serum levels of biomarkers of alcohol use: Gamma-glutamyltransferase (GGT) at study endpoint in study completers

Outcome measures

Outcome measures
Measure	Lamotrigine n=13 Participants Add-on lamotrigine plus pre-existing mood stabilizing medication regimen. Active fixed-dose drug titration from 25-200 mg/day over first six weeks, 200 mg/day fixed-dose maintenance for second six weeks Lamotrigine: Six week titration from 25 mg/day to 200 mg/day, then 200 mg/day maintenance for additional six weeks	Placebo n=12 Participants Add-on placebo plus pre-existing mood stabilization regimen for 12 weeks Placebo: Placebo once daily for 12 weeks
Biomarkers of Alcohol Use: Gamma-glutamyltransferase (GGT)	62.5 Units per liter (U/L) Standard Deviation 139.4	22.9 Units per liter (U/L) Standard Deviation 10.7

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: All randomized subjects (total n=43) included in analysis at baseline. Study completers only (total n=25) included in analysis at study endpoint.

Scores on the Montgomery-Asberg Depression Rating Scale (MADRS) at baseline (all randomized subjects) and at study endpoint (study completers). Scores represent total summed score of ten (10) subscale items; minimum = 0, maximum = 60, higher scores indicate worse outcomes.

Outcome measures

Outcome measures
Measure	Lamotrigine n=21 Participants Add-on lamotrigine plus pre-existing mood stabilizing medication regimen. Active fixed-dose drug titration from 25-200 mg/day over first six weeks, 200 mg/day fixed-dose maintenance for second six weeks Lamotrigine: Six week titration from 25 mg/day to 200 mg/day, then 200 mg/day maintenance for additional six weeks	Placebo n=22 Participants Add-on placebo plus pre-existing mood stabilization regimen for 12 weeks Placebo: Placebo once daily for 12 weeks
Montgomery-Asberg Depression Rating Scale (MADRS) Score Baseline MADRS score	9.86 units on a scale Standard Deviation 5.34	12.05 units on a scale Standard Deviation 6.21
Montgomery-Asberg Depression Rating Scale (MADRS) Score MADRS score at study endpoint	6.93 units on a scale Standard Deviation 5.36	9.18 units on a scale Standard Deviation 5.67

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Baseline YMRS scores include all randomized subjects (total n=43). Study endpoint YMRS scores include study completers only (total n=25).

Mania/hypomania symptoms at study endpoint as assessed by the Young Mania Rating Scale (YMRS) at baseline (all randomized subjects) and at study endpoint (study completers). Scores represent total summed score of eleven (11) subscale items; minimum = 0, maximum = 60, higher scores indicate worse outcomes.

Outcome measures

Outcome measures
Measure	Lamotrigine n=21 Participants Add-on lamotrigine plus pre-existing mood stabilizing medication regimen. Active fixed-dose drug titration from 25-200 mg/day over first six weeks, 200 mg/day fixed-dose maintenance for second six weeks Lamotrigine: Six week titration from 25 mg/day to 200 mg/day, then 200 mg/day maintenance for additional six weeks	Placebo n=22 Participants Add-on placebo plus pre-existing mood stabilization regimen for 12 weeks Placebo: Placebo once daily for 12 weeks
Young Mania Rating Scale (YMRS) Scores Baseline YMRS scores	7.30 score on a scale Standard Deviation 4.50	9.25 score on a scale Standard Deviation 5.58
Young Mania Rating Scale (YMRS) Scores Endpoint YMRS scores	5.50 score on a scale Standard Deviation 2.65	7.40 score on a scale Standard Deviation 4.03

SECONDARY outcome

Timeframe: Study endpoint 12 weeks after randomization

Population: Sample analyzed includes study completers only (total n=25) as this measure was obtained at study endpoint.

Adjusted scale scores (T scores) on the California Verbal Learning Test (CVLT) of verbal working memory at study endpoint. CVLT Trials 1-5 Free Recall Total measures the sum of all word list items correctly recalled on learning trials 1 through 5. This raw score is converted to a T-score (mean = 50; SD=10) with higher scores indicating better performance.

Outcome measures

Outcome measures
Measure	Lamotrigine n=13 Participants Add-on lamotrigine plus pre-existing mood stabilizing medication regimen. Active fixed-dose drug titration from 25-200 mg/day over first six weeks, 200 mg/day fixed-dose maintenance for second six weeks Lamotrigine: Six week titration from 25 mg/day to 200 mg/day, then 200 mg/day maintenance for additional six weeks	Placebo n=12 Participants Add-on placebo plus pre-existing mood stabilization regimen for 12 weeks Placebo: Placebo once daily for 12 weeks
Neurocognitive Performance (California Verbal Learning Test)	58.9 T scores Standard Deviation 14.6	52.1 T scores Standard Deviation 12.5

Adverse Events

Lamotrigine

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lamotrigine n=21 participants at risk Add-on lamotrigine plus pre-existing mood stabilizing medication regimen. Active fixed-dose drug titration from 25-200 mg/day over first six weeks, 200 mg/day fixed-dose maintenance for second six weeks Lamotrigine: Six week titration from 25 mg/day to 200 mg/day, then 200 mg/day maintenance for additional six weeks	Placebo n=22 participants at risk Add-on placebo plus pre-existing mood stabilization regimen for 12 weeks Placebo: Placebo once daily for 12 weeks
Psychiatric disorders Hospitalization	4.8% 1/21 • Number of events 1 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)	4.5% 1/22 • Number of events 1 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)
Surgical and medical procedures Hospitalization (medical) after assault	0.00% 0/21 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)	4.5% 1/22 • Number of events 1 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)

Other adverse events

Other adverse events
Measure	Lamotrigine n=21 participants at risk Add-on lamotrigine plus pre-existing mood stabilizing medication regimen. Active fixed-dose drug titration from 25-200 mg/day over first six weeks, 200 mg/day fixed-dose maintenance for second six weeks Lamotrigine: Six week titration from 25 mg/day to 200 mg/day, then 200 mg/day maintenance for additional six weeks	Placebo n=22 participants at risk Add-on placebo plus pre-existing mood stabilization regimen for 12 weeks Placebo: Placebo once daily for 12 weeks
General disorders Headache	14.3% 3/21 • Number of events 3 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)	4.5% 1/22 • Number of events 1 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)
Skin and subcutaneous tissue disorders Erythema / skin discoloration	9.5% 2/21 • Number of events 2 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)	9.1% 2/22 • Number of events 2 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)
Skin and subcutaneous tissue disorders Papular skin eruption	9.5% 2/21 • Number of events 2 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)	4.5% 1/22 • Number of events 1 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)
Skin and subcutaneous tissue disorders Pruritus	4.8% 1/21 • Number of events 1 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)	4.5% 1/22 • Number of events 1 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)
Gastrointestinal disorders Nausea	9.5% 2/21 • Number of events 2 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)	4.5% 1/22 • Number of events 1 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)
General disorders Flu-like symptoms	4.8% 1/21 • Number of events 1 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)	4.5% 1/22 • Number of events 1 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)
Nervous system disorders Tremor	0.00% 0/21 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)	9.1% 2/22 • Number of events 2 • 18 weeks (two-week baseline assessment phase, 12 week active medication phase, 4 week safety phase after medication discontinuation)

Additional Information

Bryan K. Tolliver, MD PhD

Medical University of South Carolina

Phone: 843-792-4869

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place