Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03271528
Other study ID # H-36766
Secondary ID 1R21AA026389-01
Status Completed
Phase Phase 1
First received
Last updated
Start date April 15, 2018
Est. completion date August 31, 2020

Study information

Verified date May 2021
Source Boston Medical Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a double-blind, randomized, placebo-controlled, crossover design trial tested the effect of lacosamide on alcohol self-administration and craving following a priming dose of alcohol. The specific objective of this study was to determine whether lacosamide, a novel anticonvulsant that is FDA-approved for treating partial seizures, has effects on alcohol craving and consumption.


Description:

The present proposal was intended to answer the call for accelerating drug development by exploring the potential of a novel anticonvulsant, lacosamide, as a candidate medication for the treatment of alcohol use disorder (AUD). This drug, which is approved for the treatment of seizure disorders, has unique pharmacological actions that include enhancement of slow sodium channel inactivation and inhibition of collapsin response mediator protein-2 (CRMP-2). Alcohol consumption in mice that had knockdown of CRMP-2 within the nucleus accumbens was decreased from levels seen in control animals. In rodent studies, lacosamide administration has produced reductions in 'excessive' drinking and has experimentally-induced decreased expression of the CRMP-2 protein. These findings implicate CRMP-2 as playing a role in the regulation of alcohol consumption. None of the FDA-approved AUD medications or medications commonly used off-label to treat AUD target this CRMP-2 pathway, making lacosamide a promising compound for AUD drug development. The aims of this study were to: 1) test the effects of lacosamide on alcohol self-administration and craving, 2) test the effects of 7 days of lacosamide administration on cognitive function, and 3) test the effects of lacosamide on alcohol consumption and craving during a 7-day period of exposure. The effects of 7 days of lacosamide (300mg) or placebo were evaluated in a human laboratory using an alcohol self-administration methodology. In this within-subjects crossover design, heavy drinkers (N=27) were randomized to the order of exposure (lacosamide or placebo) prior to completing two alcohol self-administration trials. Subjects received a priming drink of alcohol and had access to 8 alcoholic drinks over a 2-hour period. The investigators anticipated that subjects would consume less alcohol during an alcohol self-administration trial when receiving lacosamide compared to when they are receiving placebo. Significant lacosamide-induced reductions in the quantity of alcohol self-administered are considered to be an indication that this drug may have value as an AUD medication. This study may provide a rationale for phase II clinical studies testing lacosamide with a treatment-seeking AUD population. These results should also help to spur further pre-clinical investigation into the role play by CRMP-2 in regulating both alcohol consumption and alcohol seeking behaviors.


Recruitment information / eligibility

Status Completed
Enrollment 66
Est. completion date August 31, 2020
Est. primary completion date August 31, 2020
Accepts healthy volunteers No
Gender All
Age group 21 Years to 55 Years
Eligibility Subject Inclusion Criteria 1. 21-55 years of age 2. Can provide proof of age with state-issued or federal picture ID 3. Exceeds safe weekly drinking limits (=14 drinks for women or =21 drinks for men per week) 4. Reports at least an average of one episode per week of binge drinking (>3 for women, >4 for men) in the four weeks prior to baseline screening 5. Meets DSM-5 criteria for mild alcohol use disorder or greater severity. 6. Has a smartphone to complete some of the study assessments. Subject Exclusion Criteria 1. Currently seeking treatment for alcohol problems 2. Clinical Institute Withdrawal Assessment at >10 3. DSM-5 diagnosis of current major depression, bipolar disorder, schizophrenia, bulimia/anorexia, dementia, or a substance use disorder other than alcohol, nicotine, marijuana or caffeine 4. If female, pregnant, nursing, or have plans to become pregnant 5. If female, does not agree to use an accepted form of birth control 6. Is currently using medications for which alcohol is a contraindication 7. Has a medical or mental health condition for which further alcohol exposure at the planned dose range would be contraindicated. 8. Current risk of suicidality (MINI suicidality score greater than 8 (low risk) or Yes to the ideation question #4 of the C-SSRS) 9. Has a history of myocardial infarction, congestive heart failure, has a risk for the development of heart block, or are taking medications that can decrease conduction through the atrial ventricular node. 10. Has previous exposure to lacosamide 11. Has received any form of counseling, self-help, pharmacotherapy, or other intervention to treat AUD in the past 90 days. 12. Is unwilling to suspend use of multivitamins that contain riboflavin during study participation 13. Has urine toxicology results positive for cocaine, opioids, amphetamines, buprenorphine, methadone, or methamphetamines 14. Liver function values AST or ALT are twice the normal limit 15. GFR <80 mL/min 16. Unable to comfortably abstain from nicotine for a period of 8 hours.

Study Design


Intervention

Drug:
Lacosamide
Lacosamide titration was done to a target dose of 300mg. Participants took 100 mg of lacosamide once on day 1, 100 mg twice per day from day 2 through day 6 (200 mg daily total), on day 7 the lacosamide dose was increased to 150 mg twice daily (300 mg daily total), and on day 8 the participant took one dose of 150 mg.
Placebo oral capsule
Participants took a placebo oral capsule once on day 1, twice per day from day 2 to day 7, and once on day 8.

Locations

Country Name City State
United States Boston University Psychiatry Research Center, Clinical Studies Unit Boston Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
Boston Medical Center National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Alcohol Consumption in Alcohol Self-Administration Trials Alcohol consumption will be measured by using a graduated cylinder to determine the amount of alcohol given to the subject that was consumed. This outcome will be measured as standard drink units. A standard drink contains approximately 0.6 fluid ounces of pure alcohol. 2 hours
Secondary Verbal Fluency: Controlled Word Association (COWAT) The Controlled Word Association (COWAT) is a verbal fluency test that measures the spontaneous production of words beginning with some designated letter. The participant is asked to name words beginning with a given letter, excluding proper nouns, for one minute and this procedure is repeated three times with a different letter each time. A different set of letters was used in each of the two alcohol self-administration trials: C-F-L and P-R-W. The examiner writes down the words provided by the participant on a piece of paper. This test is scored by counting the number of words generated by the subject for each letter, then adding the scores for each of the three letters to calculate a total test score. The lowest possible score is 0 and there is no upper limit to the score range. A higher score is indicative of better outcomes (I.e. better verbal fluency). 3 minutes
Secondary Cognitive Function: Spatial Span Forward The Wechsler Memory Scale (WMS-III) Spatial Span test will be used to assess subjects' working memory. Subjects will be shown a sequence of block tapping and asked to repeat back an increasing number of tapped blocks in the same order. Each of the 16 items on this test is scored 0 (incorrect answer) or 1 (correct answer). The total score is calculated by adding the scores for each of the 16 items. The total score range is 0-16. Higher scores are indicative of higher levels of working memory (better outcome) and lower scores are indicative of lesser working memory function (worse outcome). 10 minutes
Secondary Cognitive Function: Spatial Span Backward The Wechsler Memory Scale (WMS-III) Spatial Span test will be used to assess subjects' working memory. Subjects will be shown a sequence of block tapping and asked to repeat back an increasing number of tapped blocks in the opposite order. Each of the 16 items on this test is scored 0 (incorrect answer) or 1 (correct answer). The total score is calculated by adding the scores for each of the 16 items. The total score range is 0-16. Higher scores are indicative of higher levels of working memory (better outcome) and lower scores are indicative of lesser working memory function (worse outcome). 10 minutes
Secondary Cognitive Function: Digit Span Forward The Wechsler Adult Intelligence Scale (WAIS-IV) Digit Span test will be used to assess subjects' working memory. Subjects will be read and asked to repeat back an increasing number of digits in the same order. Each of the 16 items on this test is scored 0 (incorrect answer) or 1 (correct answer). The total score is calculated by adding the scores for each of the 16 items. The total score range is 0-16. Higher scores are indicative of higher levels of working memory (better outcome) and lower scores are indicative of lesser working memory function (worse outcome). 10 minutes
Secondary Cognitive Function: Digit Span Backward The Wechsler Adult Intelligence Scale (WAIS-IV) Digit Span test will be used to assess subjects' working memory. Subjects will be read and asked to repeat back an increasing number of digits in the opposite order. Each of the 16 items on this test is scored 0 (incorrect answer) or 1 (correct answer). The total score is calculated by adding the scores for each of the 16 items. The total score range is 0-16. Higher scores are indicative of higher levels of working memory (better outcome) and lower scores are indicative of lesser working memory function (worse outcome). 10 minutes
Secondary Cognitive Function: Digit Span Sequencing The Wechsler Adult Intelligence Scale (WAIS-IV) Digit Span test will be used to assess subjects' working memory. Subjects will be read and asked to repeat back an increasing number of digits in ascending order. Each of the 16 items on this test is scored 0 (incorrect answer) or 1 (correct answer). The total score is calculated by adding the scores for each of the 16 items. The total score range is 0-16. Higher scores are indicative of higher levels of working memory (better outcome) and lower scores are indicative of lesser working memory function (worse outcome). 10 minutes
Secondary Alcohol Craving: Obsessive-Compulsive Drinking Scale (OCDS) Pretrial The Obsessive-Compulsive Drinking Scale (OCDS) is a quick and reliable 14-item self-rating instrument that provides a total score that measures some cognitive aspects of alcohol craving (obsessive and compulsive drinking). Each of the 14 items is scored from 0 to 4. The total score is calculated by adding the scores for each of the 14 items. The total score range is 0-56. Higher scores are indicative of more obsessive or compulsive drinking and lower scores are indicative of less obsessive or compulsive drinking. 5 minutes
Secondary Alcohol Craving: Visual Analog Scale (VAS) Pretrial Alcohol craving was measured by self report with the Visual Analog Scale (VAS). The VAS is a straight horizontal line with one end indicating no alcohol craving and the other end indicating intense alcohol craving. The participant marks a point on the line that matches their present amount of alcohol craving. Location of the point on the line is measured for a score range of 0-100. A lower score indicates less craving for alcohol and a higher score indicated more craving for alcohol. 1 minute
Secondary Alcohol Craving: Visual Analog Scale (VAS) Observation Period, Minute 10 Alcohol craving was measured by self report with the Visual Analog Scale (VAS). The VAS is a straight horizontal line with one end indicating no alcohol craving and the other end indicating intense alcohol craving. The participant marks a point on the line that matches their present amount of alcohol craving. Location of the point on the line is measured for a score range of 0-100. A lower score indicates less craving for alcohol and a higher score indicated more craving for alcohol. 1 minute
Secondary Alcohol Craving: Visual Analog Scale (VAS) Observation Period, Minute 20 Alcohol craving was measured by self report with the Visual Analog Scale (VAS). The VAS is a straight horizontal line with one end indicating no alcohol craving and the other end indicating intense alcohol craving. The participant marks a point on the line that matches their present amount of alcohol craving. Location of the point on the line is measured for a score range of 0-100. A lower score indicates less craving for alcohol and a higher score indicated more craving for alcohol. 1 minute
Secondary Alcohol Craving: Visual Analog Scale (VAS) Observation Period, Minute 30 Alcohol craving was measured by self report with the Visual Analog Scale (VAS). The VAS is a straight horizontal line with one end indicating no alcohol craving and the other end indicating intense alcohol craving. The participant marks a point on the line that matches their present amount of alcohol craving. Location of the point on the line is measured for a score range of 0-100. A lower score indicates less craving for alcohol and a higher score indicated more craving for alcohol. 1 minute
Secondary Alcohol Craving: Visual Analog Scale (VAS) Observation Period, Minute 40 Alcohol craving was measured by self report with the Visual Analog Scale (VAS). The VAS is a straight horizontal line with one end indicating no alcohol craving and the other end indicating intense alcohol craving. The participant marks a point on the line that matches their present amount of alcohol craving. Location of the point on the line is measured for a score range of 0-100. A lower score indicates less craving for alcohol and a higher score indicated more craving for alcohol. 1 minute
Secondary Alcohol Craving: Visual Analog Scale (VAS) Self-Administration Blocks 1 and 2, Minute 30 Alcohol craving was measured by self report with the Visual Analog Scale (VAS). The VAS is a straight horizontal line with one end indicating no alcohol craving and the other end indicating intense alcohol craving. The participant marks a point on the line that matches their present amount of alcohol craving. Location of the point on the line is measured for a score range of 0-100. A lower score indicates less craving for alcohol and a higher score indicated more craving for alcohol. 1 minute
Secondary Alcohol Craving: Visual Analog Scale (VAS) Self-Administration Blocks 1 and 2, Minute 60 Alcohol craving was measured by self report with the Visual Analog Scale (VAS). The VAS is a straight horizontal line with one end indicating no alcohol craving and the other end indicating intense alcohol craving. The participant marks a point on the line that matches their present amount of alcohol craving. Location of the point on the line is measured for a score range of 0-100. A lower score indicates less craving for alcohol and a higher score indicated more craving for alcohol. 1 minute
Secondary Alcohol Craving: Visual Analog Scale (VAS) Self-Administration Blocks 1 and 2, Minute 90 Alcohol craving was measured by self report with the Visual Analog Scale (VAS). The VAS is a straight horizontal line with one end indicating no alcohol craving and the other end indicating intense alcohol craving. The participant marks a point on the line that matches their present amount of alcohol craving. Location of the point on the line is measured for a score range of 0-100. A lower score indicates less craving for alcohol and a higher score indicated more craving for alcohol. 1 minute
Secondary Alcohol Craving: Visual Analog Scale (VAS) Self-Administration Blocks 1 and 2, Minute 120 Alcohol craving was measured by self report with the Visual Analog Scale (VAS). The VAS is a straight horizontal line with one end indicating no alcohol craving and the other end indicating intense alcohol craving. The participant marks a point on the line that matches their present amount of alcohol craving. Location of the point on the line is measured for a score range of 0-100. A lower score indicates less craving for alcohol and a higher score indicated more craving for alcohol. 1 minute
Secondary Alcohol Craving: Alcohol Urge Questionnaire (AUQ) Self-Administration Blocks 1 and 2, Minute 30 The Alcohol Urge Questionnaire (AUQ) is an 8-item self report that measures the participant's urge for an alcoholic drink at the time the questionnaire is completed. Questions are in the form of a 7-point Likert scale (from strongly disagree to strongly agree) and the participant selects the extent to which they disagree or agree with the 8 statements relating to desire to drink, expectation of a desired outcome from drinking, and inability to avoid drinking if alcohol was available. Each of the 8 items is scored 1-7. The total score is calculated by adding the scores for each of the items. The total score range is 8-56. Lower scores indicate less urge for alcohol and higher scores indicate more urge for alcohol. 1 minute
Secondary Alcohol Craving: Alcohol Urge Questionnaire (AUQ) Self-Administration Blocks 1 and 2, Minute 60 The Alcohol Urge Questionnaire (AUQ) is an 8-item self report that measures the participant's urge for an alcoholic drink at the time the questionnaire is completed. Questions are in the form of a 7-point Likert scale (from strongly disagree to strongly agree) and the participant selects the extent to which they disagree or agree with the 8 statements relating to desire to drink, expectation of a desired outcome from drinking, and inability to avoid drinking if alcohol was available. Each of the 8 items is scored 1-7. The total score is calculated by adding the scores for each of the items. The total score range is 8-56. Lower scores indicate less urge for alcohol and higher scores indicate more urge for alcohol. 1 minute
Secondary Alcohol Craving: Alcohol Urge Questionnaire (AUQ) Self-Administration Blocks 1 and 2, Minute 90 The Alcohol Urge Questionnaire (AUQ) is an 8-item self report that measures the participant's urge for an alcoholic drink at the time the questionnaire is completed. Questions are in the form of a 7-point Likert scale (from strongly disagree to strongly agree) and the participant selects the extent to which they disagree or agree with the 8 statements relating to desire to drink, expectation of a desired outcome from drinking, and inability to avoid drinking if alcohol was available. Each of the 8 items is scored 1-7. The total score is calculated by adding the scores for each of the items. The total score range is 8-56. Lower scores indicate less urge for alcohol and higher scores indicate more urge for alcohol. 1 minute
Secondary Alcohol Craving: Alcohol Urge Questionnaire (AUQ) Self-Administration Blocks 1 and 2, Minute 120 The Alcohol Urge Questionnaire (AUQ) is an 8-item self report that measures the participant's urge for an alcoholic drink at the time the questionnaire is completed. Questions are in the form of a 7-point Likert scale (from strongly disagree to strongly agree) and the participant selects the extent to which they disagree or agree with the 8 statements relating to desire to drink, expectation of a desired outcome from drinking, and inability to avoid drinking if alcohol was available. Each of the 8 items is scored 1-7. The total score is calculated by adding the scores for each of the items. The total score range is 8-56. Lower scores indicate less urge for alcohol and higher scores indicate more urge for alcohol. 1 minute
See also
  Status Clinical Trial Phase
Recruiting NCT04788004 - Long-term Recovery: Longitudinal Study of Neuro-behavioral Markers of Recovery and Precipitants of Relapse
Recruiting NCT05684094 - Mechanisms of Risky Alcohol Use in Young Adults: Linking Sleep to Reward- and Stress-Related Brain Function N/A
Completed NCT03406039 - Testing the Efficacy of an Online Integrated Treatment for Comorbid Alcohol Misuse and Emotional Problems N/A
Completed NCT03573167 - Mobile Phone-Based Motivational Interviewing in Kenya N/A
Completed NCT04817410 - ED Initiated Oral Naltrexone for AUD Phase 1
Active, not recruiting NCT04267692 - Harm Reduction Talking Circles for American Indians and Alaska Natives With Alcohol Use Disorders N/A
Completed NCT03872128 - The Role of Neuroactive Steroids in Stress, Alcohol Craving and Alcohol Use in Alcohol Use Disorders Phase 1
Completed NCT02989662 - INIA Stress and Chronic Alcohol Interactions: Glucocorticoid Antagonists in Heavy Drinkers Phase 1/Phase 2
Recruiting NCT06030154 - Amplification of Positivity for Alcohol Use N/A
Active, not recruiting NCT05419128 - Family-focused vs. Drinker-focused Smartphone Interventions to Reduce Drinking-related Consequences of COVID-19 N/A
Completed NCT04564807 - Testing an Online Insomnia Intervention N/A
Completed NCT04284813 - Families With Substance Use and Psychosis: A Pilot Study N/A
Completed NCT04203966 - Mental Health and Well-being of People Who Seek Help From Their Member of Parliament
Recruiting NCT05861843 - Craving Assessment in Patients With Alcohol Use Disorder Using Virtual Reality Exposure
Terminated NCT04404712 - FAAH Availability in Psychiatric Disorders: A PET Study Early Phase 1
Enrolling by invitation NCT04128761 - Decreasing the Temporal Window in Individuals With Alcohol Use Disorder N/A
Not yet recruiting NCT06337721 - Preventing Alcohol Use Disorders and Alcohol-Related Harms in Pacific Islander Young Adults N/A
Not yet recruiting NCT06163651 - Evaluating a One-Year Version of the Parent-Child Assistance Program N/A
Not yet recruiting NCT06444243 - Psilocybin-assisted Therapy for Alcohol Use Disorder Phase 2
Enrolling by invitation NCT02544581 - Preliminary Analysis of the Soberlink Alcohol Breath Analyzer System's (SABA) Clinical Utility During Aftercare N/A