Effects of Levetiracetam (Keppra) on Alcohol Consumption

NCT01168687 | Completed Results

• 2 other identifiers: H1815-29512-02W81XWH-05-1-0215
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The overall goals of this study are to (1) expand knowledge about interactions of levetiracetam with alcohol by assessing the effects of levetiracetam compared to placebo in moderate and heavy social alcohol users and (2) to test the AccuswayTM platform as a tool to measure postural control (which has been used as a marker of intoxication) and the effects of levetiracetam on postural control.

Conditions

Alcohol Abuse; Drug Abuse

Keywords

keppra; levetiracetam; alcoholism; genetics; subjective report

Outcome Measures

Primary Outcomes (1)

• Standard Alcoholic Drinks Per Treatment Period

  The primary outcome of this study is to determine the effect of levetiracetam on alcohol consumption as measured by change in # of drinks during each treatment period.

  During each 14 day treatment period

Study Arms (2)

Group A

EXPERIMENTAL

Twenty moderate to heavy social alcohol users will receive 250 mg of levetiracetam BID (500 mg/day) or placebo x 7 days and will be titrated to a maximum dose of 500 mg of levetiracetam BID (1,000 mg/day) x 7 days.

Drug: Levetiracetam (Keppra); Drug: Placebo

Group B

EXPERIMENTAL

Twenty moderate to heavy social alcohol users will receive 500 mg levetiracetam BID (1000 mg/day) or placebo x 7 days and will be titrated to a maximum dose of 1000 mg levetiracetam BID (2,000 mg per day) x 7 days.

Drug: Levetiracetam (Keppra); Drug: Placebo

Interventions

Levetiracetam (Keppra) DRUG

Group A: Twenty moderate to heavy social alcohol users will receive 250 mg of levetiracetam BID (500 mg/day) or placebo x 7 days and will be titrated to a maximum dose of 500 mg of levetiracetam BID (1,000 mg/day) x 7 days. Group B: Twenty moderate to heavy social alcohol users will receive 500 mg levetiracetam BID (1000 mg/day) or placebo x 7 days and will be titrated to a maximum dose of 1000 mg levetiracetam BID (2,000 mg per day) x 7 days.

Also known as: Keppra

Group A; Group B

Placebo DRUG

Group A; Group B

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults who are social drinkers 21 and 50 years of age.
• Moderate to heavy social drinkers (women=7-21 drinks/week, men=7-25 drinks/week).
• Body Mass Index (BMI)\>18 and \<30.
• If female, must be non-lactating, not pregnant, and using a reliable contraception method (i.e. abstinence, intrauterine device \[IUD\], hormonal birth control, or double barrier method \[male condom, female condom, or diaphragm plus a spermicidal agent such as contraceptive foam, jelly or cream\]).
• Able and willing to provide written informed consent.
• Able to understand and follow the instructions of the investigator, and understand all rating scales.
• Have a negative urine drug screen at all visits, with the exception of cannabinoids.

You may not qualify if:

• Positive urine drug screen, except cannabinoids. Occasional cannabinoid use is allowed, however daily use, dependence, or if considered more than a casual user by study physician, subject will be excluded.
• Use of cocaine, amphetamines or other stimulants, hallucinogens, ecstasy or other psychoactive drugs, greater than 10 times in the last 24 months or at anytime in the past 60 days.
• Lifetime use of PCP or ketamine greater than 10 times, or at any time in the last 24 months.
• History of abusing inhalants (such as glue, toluene or other volatile substances).
• Current or past dependence on, or addiction to any psychoactive drug (except nicotine or caffeine) including alcohol, as determined by the study physician's assessment.
• Current or prior enrollment in an alcohol or other drug treatment program, or current legal problems relating to alcohol or other drug use, including awaiting trial or supervision by a parole or probation officer.
• Binge drinking more than three times per week (binge defined as \>5 standard drinks in one session).
• Alcohol consumption \>21 drinks/week for women and \>25 drinks/week for men.
• Currently trying to quit alcohol and/or recreational drug use.
• Positive for lifetime abnormal opioid use or prescription drug abuse.
• Clinically significant medical or psychiatric illness (including anxiety or panic disorders) as determined by screening blood tests, medical history, and physical exam performed or reviewed by the study physician.
• Bilirubin more than 2 times the normal upper limit.
• AST (SGOT), ALT (SGPT), or alkaline phosphatase more than 2 times the normal upper limit.
• Body Mass Index \>30 or \<18
• Pregnancy or a woman of child bearing potential not currently using an adequate means of contraception.

Sponsors & Collaborators

• University of California, San Francisco: lead
• United States Department of Defense: collaborator
• University of California: collaborator

Study Sites (1)

Children's Hospital Oakland Research Institute- CRC

Berkeley, California, 94705, United States

Location

Related Publications (22)

• Angehagen M, Margineanu DG, Ben-Menachem E, Ronnback L, Hansson E, Klitgaard H. Levetiracetam reduces caffeine-induced Ca2+ transients and epileptiform potentials in hippocampal neurons. Neuroreport. 2003 Mar 3;14(3):471-5. doi: 10.1097/00001756-200303030-00035.

  PMID: 12634506 BACKGROUND

• Ardid D, Lamberty Y, Alloui A, Coudore-Civiale MA, Klitgaard H, Eschalier A. Antihyperalgesic effect of levetiracetam in neuropathic pain models in rats. Eur J Pharmacol. 2003 Jul 18;473(1):27-33. doi: 10.1016/s0014-2999(03)01933-2.

  PMID: 12877934 BACKGROUND

• Brockmoller J, Thomsen T, Wittstock M, Coupez R, Lochs H, Roots I. Pharmacokinetics of levetiracetam in patients with moderate to severe liver cirrhosis (Child-Pugh classes A, B, and C): characterization by dynamic liver function tests. Clin Pharmacol Ther. 2005 Jun;77(6):529-41. doi: 10.1016/j.clpt.2005.02.003.

  PMID: 15961984 BACKGROUND

• Cataldi M, Lariccia V, Secondo A, di Renzo G, Annunziato L. The antiepileptic drug levetiracetam decreases the inositol 1,4,5-trisphosphate-dependent [Ca2+]I increase induced by ATP and bradykinin in PC12 cells. J Pharmacol Exp Ther. 2005 May;313(2):720-30. doi: 10.1124/jpet.104.079327. Epub 2005 Jan 11.

  PMID: 15644427 BACKGROUND

• Dong M, Yeh F, Tepp WH, Dean C, Johnson EA, Janz R, Chapman ER. SV2 is the protein receptor for botulinum neurotoxin A. Science. 2006 Apr 28;312(5773):592-6. doi: 10.1126/science.1123654. Epub 2006 Mar 16.

  PMID: 16543415 BACKGROUND

• Grunewald R. Levetiracetam in the treatment of idiopathic generalized epilepsies. Epilepsia. 2005;46 Suppl 9:154-60. doi: 10.1111/j.1528-1167.2005.00329.x.

  PMID: 16302890 BACKGROUND

• Kim C, Jun K, Lee T, Kim SS, McEnery MW, Chin H, Kim HL, Park JM, Kim DK, Jung SJ, Kim J, Shin HS. Altered nociceptive response in mice deficient in the alpha(1B) subunit of the voltage-dependent calcium channel. Mol Cell Neurosci. 2001 Aug;18(2):235-45. doi: 10.1006/mcne.2001.1013.

  PMID: 11520183 BACKGROUND

• 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.

  PMID: 16702910 BACKGROUND

• LaMotte RH, Lundberg LE, Torebjork HE. Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal injection of capsaicin. J Physiol. 1992 Mar;448:749-64. doi: 10.1113/jphysiol.1992.sp019068.

  PMID: 1593488 BACKGROUND

• Lipscomb TR, Carpenter JA, Nathan PE. Static ataxia: a predictor of alcoholism? Br J Addict Alcohol Other Drugs. 1979 Sep;74(3):289-94. doi: 10.1111/j.1360-0443.1979.tb01350.x. No abstract available.

  PMID: 290377 BACKGROUND

• Lipscomb TR, Nathan PE. Blood alcohol level discrimination. The effects of family history of alcoholism, drinking pattern, and tolerance. Arch Gen Psychiatry. 1980 May;37(5):571-6. doi: 10.1001/archpsyc.1980.01780180085010.

  PMID: 7377914 BACKGROUND

• Lukyanetz EA, Shkryl VM, Kostyuk PG. Selective blockade of N-type calcium channels by levetiracetam. Epilepsia. 2002 Jan;43(1):9-18. doi: 10.1046/j.1528-1157.2002.24501.x.

  PMID: 11879381 BACKGROUND

• Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, Fuks B. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9861-6. doi: 10.1073/pnas.0308208101. Epub 2004 Jun 21.

  PMID: 15210974 BACKGROUND

• Madeja M, Margineanu DG, Gorji A, Siep E, Boerrigter P, Klitgaard H, Speckmann EJ. Reduction of voltage-operated potassium currents by levetiracetam: a novel antiepileptic mechanism of action? Neuropharmacology. 2003 Oct;45(5):661-71. doi: 10.1016/s0028-3908(03)00248-x.

  PMID: 12941379 BACKGROUND

• Newton PM, Orr CJ, Wallace MJ, Kim C, Shin HS, Messing RO. Deletion of N-type calcium channels alters ethanol reward and reduces ethanol consumption in mice. J Neurosci. 2004 Nov 3;24(44):9862-9. doi: 10.1523/JNEUROSCI.3446-04.2004.

  PMID: 15525770 BACKGROUND

• Pisani A, Bonsi P, Martella G, De Persis C, Costa C, Pisani F, Bernardi G, Calabresi P. Intracellular calcium increase in epileptiform activity: modulation by levetiracetam and lamotrigine. Epilepsia. 2004 Jul;45(7):719-28. doi: 10.1111/j.0013-9580.2004.02204.x.

  PMID: 15230693 BACKGROUND

• Rigo JM, Hans G, Nguyen L, Rocher V, Belachew S, Malgrange B, Leprince P, Moonen G, Selak I, Matagne A, Klitgaard H. The anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA- and glycine-gated currents. Br J Pharmacol. 2002 Jul;136(5):659-72. doi: 10.1038/sj.bjp.0704766.

  PMID: 12086975 BACKGROUND

• Rowbotham MC, Manville NS, Ren J. Pilot tolerability and effectiveness study of levetiracetam for postherpetic neuralgia. Neurology. 2003 Sep 23;61(6):866-7. doi: 10.1212/01.wnl.0000079463.16377.07. No abstract available.

  PMID: 14504347 BACKGROUND

• Schuckit MA, Smith TL, Kalmijn J. Findings across subgroups regarding the level of response to alcohol as a risk factor for alcohol use disorders: a college population of women and Latinos. Alcohol Clin Exp Res. 2004 Oct;28(10):1499-508. doi: 10.1097/01.alc.0000141814.80716.32.

  PMID: 15597082 BACKGROUND

• Saegusa H, Kurihara T, Zong S, Kazuno A, Matsuda Y, Nonaka T, Han W, Toriyama H, Tanabe T. Suppression of inflammatory and neuropathic pain symptoms in mice lacking the N-type Ca2+ channel. EMBO J. 2001 May 15;20(10):2349-56. doi: 10.1093/emboj/20.10.2349.

  PMID: 11350923 BACKGROUND

• Hatakeyama S, Wakamori M, Ino M, Miyamoto N, Takahashi E, Yoshinaga T, Sawada K, Imoto K, Tanaka I, Yoshizawa T, Nishizawa Y, Mori Y, Niidome T, Shoji S. Differential nociceptive responses in mice lacking the alpha(1B) subunit of N-type Ca(2+) channels. Neuroreport. 2001 Aug 8;12(11):2423-7. doi: 10.1097/00001756-200108080-00027.

  PMID: 11496122 RESULT

• Mitchell JM, Grossman LE, Coker AR, Messing RO. The anticonvulsant levetiracetam potentiates alcohol consumption in non-treatment seeking alcohol abusers. J Clin Psychopharmacol. 2012 Apr;32(2):269-72. doi: 10.1097/JCP.0b013e318248ba69.

  PMID: 22367657 DERIVED

MeSH Terms

Conditions

Alcoholism; Substance-Related Disorders

Interventions

Levetiracetam

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Jennifer Mitchell, Clinical Project Director
• Organization: Ernest Gallo Clinic and Research Center, UCSF

jmitchell@gallo.ucsf.edu

510-985-3100

Study Officials

• Robert O. Messing, M.D.

  UCSF; Department of Neurology; Ernest Gallo Clinic and Research Center

  PRINCIPAL INVESTIGATOR

• Jennifer M. Mitchell, Ph.D.

  UCSF; Department of Neurology; Ernest Gallo Clinic and Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2008
• First Posted: July 23, 2010
• Study Start: November 1, 2008
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2010
• Last Updated: August 28, 2020
• Results First Posted: February 25, 2013

Record last verified: 2020-08

Locations

US (1)