Efficacy and Safety of Levetiracetam in the Inpatient Treatment of Alcohol Withdrawal Syndrome

Efficacy and Safety of Levetiracetam in the Inpatient Treatment of Alcohol Withdrawal Syndrome [Sicherheit Und Wirksamkeit Von Levetiracetam (Keppra) für Die Behandlung Des stationären Alkoholentzugsyndroms]

The purpose of this study is to evaluate the efficacy and safety of levetiracetam for treating alcohol withdrawal syndrome (AWS) in inpatients (vs. placebo). The primary come-out parameter is the reduction of the total needed amount of diazepam for add-on treatment of acute alcohol withdrawal symptoms. The secondary come-out parameter are - safety criteria (AE) - reduction of alcohol withdrawal score over the days.

Study Overview

• Status: Completed
• Conditions: Alcohol Withdrawal Syndrome
• Intervention / Treatment: Drug: Levetiracetam; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Klinik für Psychiatrie und Psychotherapie
  • Berlin, Germany, 10559
    • Psychiatrische Klinik der Charité im St.-Hedwig Krankenhaus
  • Essen, Germany, 45136
    • Klinik für Psychiatrie und Suchtmedizin, Kliniken Essen Mitte
  • Rhede, Germany, 46414
    • Zentrum für Seelische Gesundheit
  • Sachen/Anhalt
    • Halle, Sachen/Anhalt, Germany, 06097
      • MLU Halle-Wittenberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ages eligible for study: 18-65 years.
• Meets criteria for alcohol dependence according to DSM-IV/ICD-10
• Known withdrawal symptoms in the past in case of discontinuation of alcohol consumption
• Hospital admission for alcohol detoxification
• Able to provide a written informed consent.
• Able to follow verbal and written instructions (incl. a sufficient knowledge of German language).
• Must be medically acceptable for study treatment. No past or present physical disorder that is likely to deteriorate during participation. No ECG abnormality which would likely worsen during participation and no clinical laboratory abnormality that would also suggest deterioration during treatment.
• Have a negative urine drug screen for benzodiazepines or heroine or methadone

Exclusion Criteria:

• Current diagnosis of any other substance dependence syndrome other than alcohol dependence (excluding nicotine and caffeine dependence).
• History of idiopathic epilepsy.
• Patient with any current clinically significant psychiatric disorder (acute suiciality) or developmental disorder (including organic mental disorder), like psychotic disorders.
• Patients with the following complications of alcoholism (lifetime): acute delirium tremens, hallucinatory alcoholic state, Korsakoff's syndrome, Wernicke encephalopathy, decomposed liver cirrhosis (Child B, C), suspected cirrhosis with the following clinical symptoms detected at clinical exam: signs of portal hypertension and signs of hepato-cellular failure, thrombocytopenia.
• Subjects with known sensitivity of previous adverse reaction to levetiracetam
• Contra-indication (hypersensitivity to levetiracetam or pyrrolidone derivatives) or known non-response to levetiracetam.
• History of severe GI disease which might render absorption of the medication difficult or produce medical instability of the patient which would include active peptic ulcer disease, ulcerative colitis, regional colitis, or evidence by history or physical exam of GI bleeding.
• Patients with any clinically significant acute or chronic progressive neurological, gastrointestinal, cardiovascular, hepatic, renal, haematological, endocrine, dermatological or respiratory disease, such as diabetes, severe infection, acute alcoholic hepatitis, or any other medical condition with significant worsening of the clinical situation of the patient that might interfere with the evaluation of study medication.
• Female patients pregnant, breast-feeding or of child bearing age and not protected by effective contraceptive such as implants, injectables, combined oral contraceptives, some IUDS, sexual abstinence, sterilization or vasectomized partner.
• Actually continuous use of pharmacological agents that are known to lower the seizure threshold or augment or decrease the alcohol withdrawal syndrome.
• Subjects with known sensitivity of previous adverse reaction to diazepam or clonidine
• Contra-indication or known non-response to diazepam or clonidine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 2	Drug: Levetiracetam; 1500-2000 mg daily add-on or Placebo Diazepam as needed; Other Names: KEPPRA
Placebo Comparator: 1: Diazepam plus Placebo	Drug: Placebo; 1500-2000 mg daily add-on or Placebo Diazepam as needed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the efficacy and safety of levetiracetam for treating alcohol withdrawal syndrome in inpatients. The primary come-out parameter is the reduction of the amount of diazepam for add-on treatment of acute alcohol withdrawal	during trial

Secondary Outcome Measures

Outcome Measure	Time Frame
Secondary come-out parameters are - safety criteria (AE) - reduction of alcohol withdrawal score over the days	during trial

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Investigators: Principal Investigator: Martin Schaefer, MD, Charité Campus Mitte, Klinik für Psychiatrie und Psychotherapie

Publications and helpful links

General Publications

• Krebs M, Leopold K, Richter C, Kienast T, Hinzpeter A, Heinz A, Schaefer M. Levetiracetam for the treatment of alcohol withdrawal syndrome: an open-label pilot trial. J Clin Psychopharmacol. 2006 Jun;26(3):347-9. doi: 10.1097/01.jcp.0000219926.49799.89. No abstract available.
• Richter C, Hinzpeter A, Schmidt F, Kienast T, Preuss UW, Plenge T, Heinz A, Schaefer M. Levetiracetam for the treatment of alcohol withdrawal syndrome: a multicenter, prospective, randomized, placebo-controlled trial. J Clin Psychopharmacol. 2010 Dec;30(6):720-5. doi: 10.1097/jcp.0b013e3181faf53e.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: September 6, 2005
• First Submitted That Met QC Criteria: September 6, 2005
• First Posted (Estimate): September 7, 2005

Study Record Updates

• Last Update Posted (Estimate): December 30, 2009
• Last Update Submitted That Met QC Criteria: December 29, 2009
• Last Verified: September 1, 2008

More Information

Terms related to this study

• Keywords: alcohol withdrawal; detoxification; Inpatients; alcohol dependence according to DSM-IV/ICD-10; withdrawal symptoms
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease; Syndrome; Substance Withdrawal Syndrome; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: Kep-F10.3.01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No