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| ID | Type | Description | Link |
|---|---|---|---|
| W81XWH-05-1-0215 | Other Grant/Funding Number | US Dept. of the Army |
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| Name | Class |
|---|---|
| United States Department of Defense | FED |
| University of California | OTHER |
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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.
The investigators propose a 42-day, double-blind, placebo-controlled crossover study in light to moderate and heavy alcohol users who are social drinkers.
The specific aims are to:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Oakland Research Institute- CRC | Berkeley | California | 94705 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12634506 | Background | 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. | |
| 12877934 | 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. |
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Enrolled participants were excluded prior to medication dosing if blood testing revealed elevated liver enzymes or if urine testing indicated a pregnancy.
Recruitment was conducted online (Craigslist) and from publicly posted flyers.
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| ID | Title | Description |
|---|---|---|
| FG000 | Group A: Crossover Between Low Dose Keppra and Placebo | 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) or will receive a double dose of placebo x 7 days. Participants on active drug for the first 14 days then crossed over to placebo after a 10-14 day washout period. Similarly, participants on placebo for the first 14 days then crossed over to active drug after a 10-14 day washout period. |
| FG001 | Group B: Crossover Between High Dose Keppra and Placebo | 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 or will receive a double dose of placebo x 7 days. Participants on active drug for the first 14 days then crossed over to placebo after a 10-14 day washout period. Similarly, participants on placebo for the first 14 days then crossed over to active drug after a 10-14 day washout period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Group A: Crossover Between Low Dose Keppra and Placebo | Group A: Twenty moderate to heavy social alcohol users (women 7-20 drinks/week --moderate 7-14 and heavy 15-20 and men 15-25 drinks/week --moderate 7-14 and heavy 15-25 drinks/week) 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) or will receive a double dose of placebo x 7 days. Participants on active drug for the first 14 days then crossed over to placebo after a 10-14 day washout period. Similarly, participants on placebo for the first 14 days then crossed over to active drug after a 10-14 day washout period. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | All study participants were used for data analysis. If there were no significant differences between the two doses of levetiracetam, data would be collapsed for analysis. | Posted | Mean | Standard Error | number of drinks per treatment period | During each 14 day treatment period |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Subjects (n = 46) Placebo | 23 moderate social drinkers. 23 heavy social drinkers. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jennifer Mitchell, Clinical Project Director | Ernest Gallo Clinic and Research Center, UCSF | 510-985-3100 | jmitchell@gallo.ucsf.edu |
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| D019966 | Substance-Related Disorders |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000077287 | Levetiracetam |
| ID | Term |
|---|---|
| D000081 | Acetamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000085 | Acetates |
| D000144 |
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|
|
| Placebo | Drug |
|
| 15961984 | 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. |
| 15644427 | 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. |
| 16543415 | 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. |
| 16302890 | 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. |
| 11520183 | 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. |
| 16702910 | 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. |
| 1593488 | 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. |
| 290377 | 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. |
| 7377914 | 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. |
| 11879381 | 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. |
| 15210974 | 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. |
| 12941379 | 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. |
| 15525770 | 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. |
| 15230693 | 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. |
| 12086975 | 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. |
| 14504347 | 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. |
| 15597082 | 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. |
| 11350923 | 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. |
| 11496122 | Result | 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. |
| 22367657 | Derived | 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. |
| BG001 | Group B: Crossover Between High Dose Keppra and Placebo | Group B: Twenty moderate to heavy social alcohol users (women 7-20 drinks/week --moderate 7-14 and heavy 15-20 and men 15-25 drinks/week --moderate 7-14 and heavy 15-25 drinks/week) 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 or will receive a double dose of placebo x 7 days. Participants on active drug for the first 14 days then crossed over to placebo after a 10-14 day washout period. Similarly, participants on placebo for the first 14 days then crossed over to active drug after a 10-14 day washout period. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
23 moderate social drinkers. 23 heavy social drinkers.
|
|
| 0 |
| 46 |
| 0 |
| 46 |
| EG001 | All Subjects (n = 46) Levetiracetam | 23 moderate social drinkers. 23 heavy social drinkers. | 0 | 46 | 0 | 46 |
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| Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D011760 | Pyrrolidinones |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |