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Gabapentin for Alcohol Withdrawal Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03012815
Recruitment Status : Completed
First Posted : January 6, 2017
Results First Posted : March 24, 2022
Last Update Posted : March 24, 2022
Sponsor:
Information provided by (Responsible Party):
Ruth E Bates, Mayo Clinic

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.

Condition or disease Intervention/treatment Phase
Alcohol Withdrawal Syndrome Drug: Gabapentin Drug: Benzodiazepines Drug: Divalproex Sodium Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective Randomized Controlled Open Label Trial of Symptom-triggered Benzodiazepine Versus Fixed-dose Gabapentin for Alcohol Withdrawal Syndrome
Actual Study Start Date : February 1, 2017
Actual Primary Completion Date : March 1, 2021
Actual Study Completion Date : March 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Gabapentin
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
Gabapentin administered as a taper
Other Name: Neurontin

Drug: Divalproex Sodium
Given in addition to gabapentin in high risk patients (i.e. seizures, TBI history, DT history)
Other Name: Depakote

Active Comparator: Benzodiazepine
Patients will receive a benzodiazepine if scoring greater than 9 on the CIWA-Ar scale.
Drug: Benzodiazepines
Benzodiazepines administered using a symptoms triggered protocol
Other Names:
  • lorazepam
  • chlordiazepoxide




Primary Outcome Measures :
  1. Mean Length of Hospital Stay [ Time Frame: Time to discharge or time to CIWA-Ar score < 10 for 36 hours (whichever came first) up to 240 hrs. ]
    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 :
  1. Number of Participants With Delirium Tremens (DT) [ Time Frame: During hospitalization (up to 240 hours) ]
    The number of participants experiencing delirium tremens during their hospitalization (between admission and discharge).

  2. Maximun Alcohol Withdrawal Severity Per CIWA-Ar Scale [ Time Frame: 4 days ]
    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

  3. Change in Sleepiness as Assessed by the Epworth Sleepiness Scale [ Time Frame: Baseline and 2 days ]
    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.

  4. Mean Total Benzodiazepine Use [ Time Frame: Time to discharge or time to CIWA-Ar score < 10 for 36 hours (whichever came first) up to 240 hrs. ]
    The total amount of benzodiazepines administered. Measured by lorazepam equivalent, mg.

  5. Number of Participants Experiencing Seizure [ Time Frame: During hospitalization (up to 240 hours). ]
    The number of subjects who developed seizure during their hospitalization.

  6. Change in Cravings as Assessed by the Penn Alcohol Craving (PACS) Scale [ Time Frame: Baseline and 2 days ]
    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)

  7. Change in Anxiety Symptoms as Measured by the Generalized Anxiety Disorder-7 (GAD-7) Scale [ Time Frame: Baseline and 2 days ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03012815


Locations
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United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
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Principal Investigator: Ruth E Bates, MD Mayo Clinic
  Study Documents (Full-Text)

Documents provided by Ruth E Bates, Mayo Clinic:
Additional Information:
Publications:
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Responsible Party: Ruth E Bates, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03012815    
Other Study ID Numbers: 16-008712
First Posted: January 6, 2017    Key Record Dates
Results First Posted: March 24, 2022
Last Update Posted: March 24, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ruth E Bates, Mayo Clinic:
gabapentin
Alcohol Withdrawal Syndrome
benzodiazepine
symptom-triggered
Additional relevant MeSH terms:
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Syndrome
Substance Withdrawal Syndrome
Disease
Pathologic Processes
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Chlordiazepoxide
Gabapentin
Lorazepam
Valproic Acid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anticonvulsants
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antimanic Agents
Antiemetics
Autonomic Agents
Gastrointestinal Agents
Hypnotics and Sedatives
GABA Modulators