Clinical trial NCT00021697: Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
Official title: A Double-Blind Controlled, Multicenter Phase II/III Study to Assess the Safety and Efficacy of AVP-923 (Dextromethorphan/Quinidine) in the Treatment of Pseudobulbar Affect in Patients With Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis
Keywords: AVP-923
Dextromethorphan
Quinidine
Pseudobulbar Affect
Lead sponsor: Avanir Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2001-08-03
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare and evaluate the safety of AVP-923 (dextromethorphan/quinidine) for the treatment of emotional lability in ALS patients.


Eligibility criteria: Inclusion:

* 18 to 80 years of age, inclusive
* Confirmed diagnosis of ALS or probable ALS
* Clinical history of pseudobulbar affect
* If female, must not be pregnant, breast-feeding, or planning a pregnancy during the course of the study, and must have a negative urine pregnancy test prior to start of study
* If female, must have been practicing an established method of birth control for at least the prior month (oral contraceptive tablets, hormonal implant device, intrauterine device, diaphragm and contraceptive cream or foam, condom with spermicide, tubal ligation, or abstinence) or be surgically sterile or post-menopausal
* Must be willing to not take any prohibited medications during participation in the study

Exclusion:

* Known sensitivity to quinidine or opiate drugs (codeine, etc.)
* On any anti-depressive medication
* Recently (within two months) diagnosed with ALS
* Currently participating in, or who within the past 30 days have participated in, the study of another investigational new drug
* Previously received treatment with co-administration of dextromethorphan and quinidine
* History of substance abuse within the past two years
* Women who are pregnant or likely to become pregnant during the course of the study

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Loma Linda University Dept. of Neurology
state: California
city: Los Angeles
country: United States
facility: UCLA School of Medicine Dept. of Neurology
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: University of Colorado Health Sciences
state: Colorado
city: Miami
country: United States
facility: University of Miami Dept. of Neurology
state: Florida
city: Chicago
country: United States
facility: Northwestern Medical School
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Columbia-Presbyterian Center Neurological Institute
state: New York
city: Syracuse
country: United States
facility: State University of New York
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center Carolinas Neuromuscular/ALS-MDA Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: MCP-Hahnemann University Dept. of Neurology
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Neurological Institute
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Health Science Center @ San Antonio
state: Texas
city: Madison
country: United States
facility: University of Wisconsin ALS Clinical Research Center
state: Wisconsin
Study officials:
References:
citation: Dark FL, McGrath JJ, Ron MA. Pathological laughing and crying. Aust N Z J Psychiatry. 1996 Aug;30(4):472-9. doi: 10.3109/00048679609065020.
citation: Smith RA, Moore SR, Gresham LS, Manley PE, Licht JM: The treatment of affective lability with dextromethorphan. Neurology 54: 604P, 1995
citation: Gallagher JP. Pathologic laughter and crying in ALS: a search for their origin. Acta Neurol Scand. 1989 Aug;80(2):114-7. doi: 10.1111/j.1600-0404.1989.tb03851.x.
citation: Wolf JK, Santana HB, Thorpy M. Treatment of "emotional incontinence" with levodopa. Neurology. 1979 Oct;29(10):1435-6. doi: 10.1212/wnl.29.10.1435-b. No abstract available.
citation: Muller U, Murai T, Bauer-Wittmund T, von Cramon DY. Paroxetine versus citalopram treatment of pathological crying after brain injury. Brain Inj. 1999 Oct;13(10):805-11. doi: 10.1080/026990599121197.
citation: Moore SR, Gresham LS, Bromberg MB, Kasarkis EJ, Smith RA. A self report measure of affective lability. J Neurol Neurosurg Psychiatry. 1997 Jul;63(1):89-93. doi: 10.1136/jnnp.63.1.89.
citation: Schadel M, Wu D, Otton SV, Kalow W, Sellers EM. Pharmacokinetics of dextromethorphan and metabolites in humans: influence of the CYP2D6 phenotype and quinidine inhibition. J Clin Psychopharmacol. 1995 Aug;15(4):263-9. doi: 10.1097/00004714-199508000-00005.
citation: Brooks BR, Crumpacker D, Fellus J, Kantor D, Kaye RE. PRISM: a novel research tool to assess the prevalence of pseudobulbar affect symptoms across neurological conditions. PLoS One. 2013 Aug 21;8(8):e72232. doi: 10.1371/journal.pone.0072232. eCollection 2013.
citation: Brooks BR, Thisted RA, Appel SH, Bradley WG, Olney RK, Berg JE, Pope LE, Smith RA; AVP-923 ALS Study Group. Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology. 2004 Oct 26;63(8):1364-70. doi: 10.1212/01.wnl.0000142042.50528.2f.