Back to resultsGabapentin for Alcohol Withdrawal Syndrome
Primary Purpose
Alcohol Withdrawal Syndrome
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Gabapentin
Benzodiazepines
Divalproex Sodium
Sponsored by
About this trial
This is an interventional treatment trial for Alcohol Withdrawal Syndrome focused on measuring gabapentin, Alcohol Withdrawal Syndrome, benzodiazepine, symptom-triggered
Eligibility Criteria
Inclusion criteria
- Prediction of Alcohol Withdrawal Severity Scale (PAWSS) score >4.
- Adults age 18 or older.
- Sufficient understanding of English.
- Hospitalized on Hospital Internal Medicine or Generose.
Exclusion criteria
- Severe renal impairment (estimated CrCl < 30).
- Intensive Care Unit (ICU) level of care.
- Not responsive due to alcohol intoxication or withdrawal.
- Already taking gabapentin more than 300 mg three times a day.
- Prescribed pregabalin.
- Primary seizure disorder.
- Acute benzodiazepine withdrawal.
- Concurrent substance use disorders (such as opioid use disorder, stimulant use disorder) if the disorder is assessed to be clinically significant. Cannabis use disorder will be allowed.
- Concurrent anticonvulsant medications for psychiatric indications (e.g. bipolar disorder) will be allowed.
- Pregnancy.
- Involuntary legal status (e.g., on court commitment).
- Patients admitted greater than 12 hours prior to potential enrollment.
- Patients receiving therapeutic dose of gabapentin (rather than continuation of home dose) prior to enrollment.
Sites / Locations
- Mayo Clinic in Rochester
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Gabapentin
Benzodiazepine
Arm Description
Patients will receive gabapentin taper over 9 days with the option to add divalproex for patients who have a history of seizures or severe withdrawal. Will still undergo CIWA-Ar scoring but will not be administered a benzodiazepine.
Patients will receive a benzodiazepine if scoring greater than 9 on the CIWA-Ar scale.
Outcomes
Primary Outcome Measures
Mean Length of Hospital Stay
The length of hospital stay for Alcohol withdrawal syndrome. The time interval between admission and either discharge or the time at which Clinical Institute Withdrawal Assessment - Alcohol revised (CIWA-Ar) scores are <10 for 36 hours (up to 240 hours). Measured in hours. CIWA-Ar measures severity of 10 observed or measured alcohol withdrawal signs or symptoms. Zero to 7 points are assigned to each item, except for the last item, which is assigned 0-4 points, with a total possible score of 67. Total score ranges from 0 (best possible outcome)-67 (worst possible outcome). Lower scores (0-8) represent fewer withdrawal symptoms and less severity, scores > 8 represent more withdrawal symptoms and greater severity
Secondary Outcome Measures
Number of Participants With Delirium Tremens (DT)
The number of participants experiencing delirium tremens during their hospitalization (between admission and discharge).
Maximun Alcohol Withdrawal Severity Per CIWA-Ar Scale
CIWA-Ar measures severity of 10 observed or measured alcohol withdrawal signs or symptoms. Zero to 7 points are assigned to each item, except for the last item, which is assigned 0-4 points, with a total possible score of 67. Total score ranges from 0 (best possible outcome)-67 (worst possible outcome). Lower scores (0-8) represent fewer withdrawal symptoms and less severity, scores > 8 represent more withdrawal symptoms and greater severity
Change in Sleepiness as Assessed by the Epworth Sleepiness Scale
The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most people engage in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their daytime sleepiness.
Mean Total Benzodiazepine Use
The total amount of benzodiazepines administered. Measured by lorazepam equivalent, mg.
Number of Participants Experiencing Seizure
The number of subjects who developed seizure during their hospitalization.
Change in Cravings as Assessed by the Penn Alcohol Craving (PACS) Scale
PACS is a 5 item self-rated scale of alcohol craving (0 = none to 6 = strong urge). Total scores range from 0 (little craving for alcohol) to 30 (irresistible urge to drink alcohol)
Change in Anxiety Symptoms as Measured by the Generalized Anxiety Disorder-7 (GAD-7) Scale
GAD-7 is GAD-7 is a 7-item self-administered scale of Generalized Anxiety Disorder symptoms (0 = not at all to 3 = nearly every day). Total scores range from 0 to 21. Total scores of 0-4 = minimal anxiety, Total scores of 5-9 = mild anxiety, total scores of 10-14 = moderate anxiety and total scores of 15-21 = severe anxiety.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03012815
Brief Title
Gabapentin for Alcohol Withdrawal Syndrome
Official Title
A Prospective Randomized Controlled Open Label Trial of Symptom-triggered Benzodiazepine Versus Fixed-dose Gabapentin for Alcohol Withdrawal Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
February 1, 2017 (Actual)
Primary Completion Date
March 1, 2021 (Actual)
Study Completion Date
March 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The current "gold-standard" for the management of alcohol withdrawal syndrome (AWS) is symptom-triggered administration of benzodiazepines. This method of treatment has several drawbacks that have been described in the literature. Thus benzodiazepine sparing agents have been evaluated for use in AWS. One of these agents that has not only shown benefit for AWS but also benefits on complete abstinence, reducing a return to heavy drinking, and cravings is gabapentin. In clinical practice at Mayo Clinic gabapentin is used for this purpose. Due to the limited reports of the safety and efficacy of a protocol involving gabapentin for AWS, a study to compare gabapentin to symptom-triggered lorazepam will be completed.
Detailed Description
The current "gold-standard" for the management of alcohol withdrawal syndrome is symptom-triggered administration of benzodiazepines. Benzodiazepines and use of a symptom-triggered approach has several drawbacks such as over administration of medication due to many subjective patient reported symptoms. Benzodiazepines may contribute to a drug-induced delirium or high dosage may necessitate transfer to an ICU setting. Abrupt withdrawal of benzodiazepines also contribute to cravings, rebound insomnia, and anxiety that have been shown to increase the risk of a return drinking.
Clinical use of gabapentin for alcohol withdrawal has been presented by Maldonado at Stanford University Hospitals. (Academy of Psychosomatic Medicine Annual Meeting, 2013-2015) At Mayo Clinic, the Psychiatry Consultation-Liaison hospital service has been recommending the use of a modified gabapentin protocol since January 2015, which has been clinically accepted on medical, surgical, and psychiatric hospital services. The purpose of this research is to investigate the reactive benzodiazepine versus proactive gabapentin approaches to AWS in a prospective, randomized, open-label study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Withdrawal Syndrome
Keywords
gabapentin, Alcohol Withdrawal Syndrome, benzodiazepine, symptom-triggered
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
88 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Gabapentin
Arm Type
Experimental
Arm Description
Patients will receive gabapentin taper over 9 days with the option to add divalproex for patients who have a history of seizures or severe withdrawal. Will still undergo CIWA-Ar scoring but will not be administered a benzodiazepine.
Arm Title
Benzodiazepine
Arm Type
Active Comparator
Arm Description
Patients will receive a benzodiazepine if scoring greater than 9 on the CIWA-Ar scale.
Intervention Type
Drug
Intervention Name(s)
Gabapentin
Other Intervention Name(s)
Neurontin
Intervention Description
Gabapentin administered as a taper
Intervention Type
Drug
Intervention Name(s)
Benzodiazepines
Other Intervention Name(s)
lorazepam, chlordiazepoxide
Intervention Description
Benzodiazepines administered using a symptoms triggered protocol
Intervention Type
Drug
Intervention Name(s)
Divalproex Sodium
Other Intervention Name(s)
Depakote
Intervention Description
Given in addition to gabapentin in high risk patients (i.e. seizures, TBI history, DT history)
Primary Outcome Measure Information:
Title
Mean Length of Hospital Stay
Description
The length of hospital stay for Alcohol withdrawal syndrome. The time interval between admission and either discharge or the time at which Clinical Institute Withdrawal Assessment - Alcohol revised (CIWA-Ar) scores are <10 for 36 hours (up to 240 hours). Measured in hours. CIWA-Ar measures severity of 10 observed or measured alcohol withdrawal signs or symptoms. Zero to 7 points are assigned to each item, except for the last item, which is assigned 0-4 points, with a total possible score of 67. Total score ranges from 0 (best possible outcome)-67 (worst possible outcome). Lower scores (0-8) represent fewer withdrawal symptoms and less severity, scores > 8 represent more withdrawal symptoms and greater severity
Time Frame
Time to discharge or time to CIWA-Ar score < 10 for 36 hours (whichever came first) up to 240 hrs.
Secondary Outcome Measure Information:
Title
Number of Participants With Delirium Tremens (DT)
Description
The number of participants experiencing delirium tremens during their hospitalization (between admission and discharge).
Time Frame
During hospitalization (up to 240 hours)
Title
Maximun Alcohol Withdrawal Severity Per CIWA-Ar Scale
Description
CIWA-Ar measures severity of 10 observed or measured alcohol withdrawal signs or symptoms. Zero to 7 points are assigned to each item, except for the last item, which is assigned 0-4 points, with a total possible score of 67. Total score ranges from 0 (best possible outcome)-67 (worst possible outcome). Lower scores (0-8) represent fewer withdrawal symptoms and less severity, scores > 8 represent more withdrawal symptoms and greater severity
Time Frame
4 days
Title
Change in Sleepiness as Assessed by the Epworth Sleepiness Scale
Description
The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most people engage in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their daytime sleepiness.
Time Frame
Baseline and 2 days
Title
Mean Total Benzodiazepine Use
Description
The total amount of benzodiazepines administered. Measured by lorazepam equivalent, mg.
Time Frame
Time to discharge or time to CIWA-Ar score < 10 for 36 hours (whichever came first) up to 240 hrs.
Title
Number of Participants Experiencing Seizure
Description
The number of subjects who developed seizure during their hospitalization.
Time Frame
During hospitalization (up to 240 hours).
Title
Change in Cravings as Assessed by the Penn Alcohol Craving (PACS) Scale
Description
PACS is a 5 item self-rated scale of alcohol craving (0 = none to 6 = strong urge). Total scores range from 0 (little craving for alcohol) to 30 (irresistible urge to drink alcohol)
Time Frame
Baseline and 2 days
Title
Change in Anxiety Symptoms as Measured by the Generalized Anxiety Disorder-7 (GAD-7) Scale
Description
GAD-7 is GAD-7 is a 7-item self-administered scale of Generalized Anxiety Disorder symptoms (0 = not at all to 3 = nearly every day). Total scores range from 0 to 21. Total scores of 0-4 = minimal anxiety, Total scores of 5-9 = mild anxiety, total scores of 10-14 = moderate anxiety and total scores of 15-21 = severe anxiety.
Time Frame
Baseline and 2 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria
Prediction of Alcohol Withdrawal Severity Scale (PAWSS) score >4.
Adults age 18 or older.
Sufficient understanding of English.
Hospitalized on Hospital Internal Medicine or Generose.
Exclusion criteria
Severe renal impairment (estimated CrCl < 30).
Intensive Care Unit (ICU) level of care.
Not responsive due to alcohol intoxication or withdrawal.
Already taking gabapentin more than 300 mg three times a day.
Prescribed pregabalin.
Primary seizure disorder.
Acute benzodiazepine withdrawal.
Concurrent substance use disorders (such as opioid use disorder, stimulant use disorder) if the disorder is assessed to be clinically significant. Cannabis use disorder will be allowed.
Concurrent anticonvulsant medications for psychiatric indications (e.g. bipolar disorder) will be allowed.
Pregnancy.
Involuntary legal status (e.g., on court commitment).
Patients admitted greater than 12 hours prior to potential enrollment.
Patients receiving therapeutic dose of gabapentin (rather than continuation of home dose) prior to enrollment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ruth E Bates, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
18052562
Citation
Furieri FA, Nakamura-Palacios EM. Gabapentin reduces alcohol consumption and craving: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2007 Nov;68(11):1691-700. doi: 10.4088/jcp.v68n1108.
Results Reference
background
PubMed Identifier
25969570
Citation
Leung JG, Hall-Flavin D, Nelson S, Schmidt KA, Schak KM. The role of gabapentin in the management of alcohol withdrawal and dependence. Ann Pharmacother. 2015 Aug;49(8):897-906. doi: 10.1177/1060028015585849. Epub 2015 May 12.
Results Reference
background
PubMed Identifier
25999438
Citation
Maldonado JR, Sher Y, Das S, Hills-Evans K, Frenklach A, Lolak S, Talley R, Neri E. Prospective Validation Study of the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) in Medically Ill Inpatients: A New Scale for the Prediction of Complicated Alcohol Withdrawal Syndrome. Alcohol Alcohol. 2015 Sep;50(5):509-18. doi: 10.1093/alcalc/agv043. Epub 2015 May 21.
Results Reference
background
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
Learn more about this trial
Gabapentin for Alcohol Withdrawal Syndrome
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