Gabapentin for Alcohol Withdrawal Syndrome

NCT03012815 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 16-008712
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

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.

Conditions

Alcohol Withdrawal Syndrome

Keywords

gabapentin; Alcohol Withdrawal Syndrome; benzodiazepine; symptom-triggered

Outcome Measures

Primary Outcomes (1)

• 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

  Time to discharge or time to CIWA-Ar score < 10 for 36 hours (whichever came first) up to 240 hrs.

Secondary Outcomes (7)

• Number of Participants With Delirium Tremens (DT)

  During hospitalization (up to 240 hours)

• Maximun Alcohol Withdrawal Severity Per CIWA-Ar Scale

  4 days

• Change in Sleepiness as Assessed by the Epworth Sleepiness Scale

  Baseline and 2 days

• Mean Total Benzodiazepine Use

  Time to discharge or time to CIWA-Ar score < 10 for 36 hours (whichever came first) up to 240 hrs.

• Number of Participants Experiencing Seizure

  During hospitalization (up to 240 hours).

Study Arms (2)

Gabapentin

EXPERIMENTAL

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.

Drug: Gabapentin; Drug: Divalproex Sodium

Benzodiazepine

ACTIVE COMPARATOR

Patients will receive a benzodiazepine if scoring greater than 9 on the CIWA-Ar scale.

Drug: Benzodiazepines

Interventions

Gabapentin DRUG

Gabapentin administered as a taper

Also known as: Neurontin

Gabapentin

Benzodiazepines DRUG

Benzodiazepines administered using a symptoms triggered protocol

Also known as: lorazepam, chlordiazepoxide

Benzodiazepine

Divalproex Sodium DRUG

Given in addition to gabapentin in high risk patients (i.e. seizures, TBI history, DT history)

Also known as: Depakote

Gabapentin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (4)

• 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.

  PMID: 18052562 BACKGROUND

• 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.

  PMID: 25969570 BACKGROUND

• 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.

  PMID: 25999438 BACKGROUND

• DeFoster RE, Morgan RJ 3rd, Leung JG, Schenzel H, Vijapura P, Kashiwagi DT, Fischer KM, Philbrick KL, Kung S. Use of Gabapentin for Alcohol Withdrawal Syndrome in the Hospital Setting: A Randomized Open-Label Controlled Trial. Subst Use Misuse. 2023;58(13):1643-1650. doi: 10.1080/10826084.2023.2236223. Epub 2023 Jul 19.

  PMID: 37469099 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Interventions

Gabapentin; Benzodiazepines; Lorazepam; Chlordiazepoxide; Valproic Acid

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzodiazepinones; Pentanoic Acids; Valerates; Fatty Acids, Volatile; Fatty Acids; Lipids

Results Point of Contact

• Title: Ruth Bates
• Organization: Mayo Clinic

Bates.Ruth@mayo.edu

507-255-8716

Study Officials

• Ruth E Bates, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 27, 2016
• First Posted: January 6, 2017
• Study Start: February 1, 2017
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: March 24, 2022
• Results First Posted: March 24, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)