Clinical trial NCT03012815: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alcohol Withdrawal Syndrome
Keywords: gabapentin
Alcohol Withdrawal Syndrome
benzodiazepine
symptom-triggered
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2017-01-06
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria

1. Prediction of Alcohol Withdrawal Severity Scale (PAWSS) score \>4.
2. Adults age 18 or older.
3. Sufficient understanding of English.
4. Hospitalized on Hospital Internal Medicine or Generose.

Exclusion criteria

1. Severe renal impairment (estimated CrCl \< 30).
2. Intensive Care Unit (ICU) level of care.
3. Not responsive due to alcohol intoxication or withdrawal.
4. Already taking gabapentin more than 300 mg three times a day.
5. Prescribed pregabalin.
6. Primary seizure disorder.
7. Acute benzodiazepine withdrawal.
8. 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.
9. Concurrent anticonvulsant medications for psychiatric indications (e.g. bipolar disorder) will be allowed.
10. Pregnancy.
11. Involuntary legal status (e.g., on court commitment).
12. Patients admitted greater than 12 hours prior to potential enrollment.
13. Patients receiving therapeutic dose of gabapentin (rather than continuation of home dose) prior to enrollment.

Primary outcomes:
measure: Mean Length of Hospital Stay
timeFrame: Time to discharge or time to CIWA-Ar score < 10 for 36 hours (whichever came first) up to 240 hrs.
Secondary outcomes:
measure: Number of Participants With Delirium Tremens (DT)
timeFrame: During hospitalization (up to 240 hours)
measure: Maximun Alcohol Withdrawal Severity Per CIWA-Ar Scale
timeFrame: 4 days
measure: Change in Sleepiness as Assessed by the Epworth Sleepiness Scale
timeFrame: Baseline and 2 days
measure: Mean Total Benzodiazepine Use
timeFrame: Time to discharge or time to CIWA-Ar score < 10 for 36 hours (whichever came first) up to 240 hrs.
measure: Number of Participants Experiencing Seizure
timeFrame: During hospitalization (up to 240 hours).
measure: Change in Cravings as Assessed by the Penn Alcohol Craving (PACS) Scale
timeFrame: Baseline and 2 days
measure: Change in Anxiety Symptoms as Measured by the Generalized Anxiety Disorder-7 (GAD-7) Scale
timeFrame: Baseline and 2 days
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Ruth E Bates, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.