Please select the eligibility criteria that correspond to the clinical trial below.
Title: Vigabatrin for Treatment of Cocaine Dependence: A Phase II Study
Brief Summary: The objective of this study is to demonstrate that a larger proportion of vigabatrin-treated subjects than placebo-treated subjects will be cocaine-free in the last 2 weeks of treatment.


Options:
A: Inclusion Criteria:

* To be included in this study, patients will be required to be either acutely hypomanic or manic as defined by the Diagnostic and Statistical Manual -IV (DSM-IV) and meet criteria for current substance abuse and/or dependence disorder within the last six months.
* Must have 4 or more episodes in the immediate 12 months prior to study entry.
* Males or females 16 - 65 years of age.
* A score of 60 or less on the Global Assessment Scale.
* Have no medical illness precluding the use of lithium or divalproex.

Exclusion Criteria:

* Patients who have had intolerable side effects to lithium levels 0.8 meq/L or divalproex levels of 50 ug/ml. Patients who have been completely non-responsive to lithium in the past will be excluded, whereas patients who have had partial responses to lithium will be permitted into the study.
* Patients with a prior history of seizure disorder, cerebral vascular disease, structural brain damage from trauma, clinically significant focal neurological abnormalities, EEG abnormalities with frank paroxysmal activity or a previous CT/MRI scan of the brain with gross structural abnormalities.
* Patients who require anticoagulant drug therapy.
* Patients who have uncontrolled gastrointestinal, renal, hepatic, endocrine, cardiovascular, pulmonary, immunological or hematological disease. Patients with alcohol-related liver disease as reflected by diffuse elevations in liver functions tests exceeding the upper limits of the normal range by 50% will be excluded.
* Patients who are pregnant or plan to become pregnant during the study.
* Patients who have received haloperidol decanoate or fluphenazine decanoate within the last 10 weeks.
* Patients who have a central nervous system (CNS) neoplasm, uncontrolled metabolic, demyelinating or progressive disorder; active CNS infection; or any progressive neurological disorder.
* Patients who are taking exogenous steroids.
* Patients who do not meet criteria for substance abuse or dependence.
B: Inclusion Criteria:

* Current DSM-IV diagnosis of cocaine dependence
* Good physical health as determined by a complete physical examination, an EKG within normal limits, and laboratory screening tests within acceptable parameters
* Seeking treatment for cocaine dependence
* At least one positive urine drug screen for cocaine at screen or baseline prior to randomization
* If female, a negative pregnancy test prior to study entry
* Agrees to use an effective method of contraception for the duration of the study
* Reads and writes English
* Willing to participate in behavioral treatment for cocaine dependence

Exclusion Criteria:

* Current DSM-IV diagnosis of dependence on any psychoactive substance other than cocaine, alcohol, nicotine, caffeine, or marijuana
* Physiological dependence on alcohol and requires medical detoxification
* Neurological or psychiatric disorders
* Any Axis 1 disorder that warrants treatment or would preclude safe participation
* Organic brain disease
* Dementia
* Bulimia and/or anorexia nervosa
* Seizure disorders or epilepsy
* Any disorder which would require ongoing treatment or which would make study agent compliance difficult
* History of suicide attempts and/or current suicidal ideation, as determined by the SCID, within the 30 days prior to screening
* Serious medical illnesses
* Mandated by the court to obtain treatment for cocaine dependence
* Expected to relocate from the study area
* AIDS diagnosis
* HIV with a CD4 positive T cell count less than 500 mm
* Any subjects on any pharmacotherapy for the treatment of AIDS or HIV will be excluded
* Active syphilis that has not been treated, or refused treatment for syphilis
* Severe or life-threatening adverse reactions to medications (including topiramate) in the past or during this clinical trial
* Currently receiving active treatment with topiramate
* Use of a drug with known potential for toxicity to a major organ system (e.g., isoniazid, methotrexate), within 30 days prior to study entry
* Pregnant or breastfeeding
* Concurrent regular use of psychotropics, including but not limited to antidepressants, anxiolytics, antipsychotics, anticonvulsants, and psychomotor stimulant-type medications, St. John's Wort, yohimbine, ginko biloba, horehound, or any other central nervous system active herbal preparations
* Use of any opiate substitutes (e.g., methadone, levo-alpha acetyl methadol, buprenorphine), within the month prior to screening
* Clinically significant test results that, in the investigator's opinion, require immediate or urgent treatment
* Fever of unknown origin or neuroleptic malignant syndrome
* Serious medical co-morbidity requiring medical intervention or close supervision
* Received inpatient or outpatient treatment for cocaine dependence within the 4 weeks prior to study entry
* Past participation in a clinical trial utilizing topiramate
* Treatment with electroconvulsive therapy within the 3 months prior to study entry
* Member of the same household of an individual enrolled in the present study
C: Inclusion Criteria:

In order to participate in the study, subjects must

* Be at least 18 years of age and no older than 55 years of age.
* Weigh more than 100 pounds.
* Have a DSM-IV diagnosis of cocaine dependence.
* Be seeking treatment for cocaine dependence.
* Have a urine sample positive for qualitative cocaine toxicology at initial screening.
* Have the ability to understand, and having understood, provide written informed consent to comply with the treatment protocol.
* Have a history and brief physical examination that demonstrate no clinically significant contraindication for participating in the study, in the judgment of the admitting physician and the Principal Investigator.
* Have normal, or, if necessary, corrected visual acuity, visual fields, and normal fundoscopy findings

Exclusion Criteria:

* In order to participate in the study, subjects must not:

  * Meet DSM-IV criteria for current dependence on any psychoactive substance other than cocaine, alcohol, nicotine, or marijuana or physiological dependence on alcohol requiring medical detoxification.
  * Have neurological or psychiatric disorders such as: psychosis, bipolar illness, major depression, organic brain disease, dementia, any disorder which would require ongoing treatment or which would make study agent compliance difficult, history of suicide attempts assessed and/or current suicidal ideation/plan.
  * Have serious medical illnesses or other potentially life threatening or progressive medical illness other than addiction that may compromise subject safety or study conduct.
  * Have a history of traumatic head injury.
  * Be mandated by a court to obtain treatment for cocaine dependence.
  * Have been treated for cocaine addiction, or abstained from cocaine use for a significant period, within the 6 months preceding screening.
  * Be unable to complete the study protocol because of probable incarceration or relocation from the clinical area.
  * Have AIDS (although AIDS is an exclusion criterion, a positive antibody titer to HIV is not).
  * Have active syphilis that has not been treated or refuse treatment for syphilis
  * Have a history of neuroleptic malignant syndrome.
  * Have known or suspected hypersensitivity to vigabatrin or any other GABAergic drug.
  * Have received a drug with known potential for toxicity to a major organ system within 30 days prior to study entry (e.g., isoniazid, methotrexate).
  * Have participated in any experimental study within 4 weeks, or participated in any clinical trial utilizing vigabatrin.
  * Be pregnant or lactating.
  * Have any clinically significant abnormal laboratory value.
  * Have had electroconvulsive therapy with the 3 months preceding screening.
  * Have had any opiate-substitutes (methadone, LAAM, buprenorphine) within 2 months preceding screening.
  * Have a history of i.v. cocaine (or other psychoactive drug) use within 2 months preceding screening.
  * Have a current or past history of seizure disorder, including alcohol- or stimulant related seizure, febrile seizure, or significant family history of idiopathic seizure disorder.
  * Have a visual field defect, or factor predisposing to visual field defects, including glaucoma, severe myopia, retinal disorder, cataracts, diabetes or uncontrolled hypertension.
  * Have my illness, condition, and use of medications, in the opinion of the Principal Investigator and the admitting physician, which would preclude safe or successful completion of the study.
  * Be using vigabatrin or any medication that could interact adversely with vigabatrin administration, based on the longest time interval of A or B below:

    * A) Five half-lives of other medication or active metabolite(s), whichever is longer;
    * B) Two weeks.
  * Be lactose intolerant.
D: Inclusion Criteria:

* Able to understand the study and provide written informed consent.
* Male or female at least 18 years of age.
* Meets DSM-IV (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition) criteria for cocaine dependence as primary diagnosis, as determined by the Substance Abuse module of SCID (Structured Clinical Interview for DSM-IV).
* Provide at least one urine sample that is positive for cocaine according to a rapid screening test.
* Seeking treatment for cocaine dependence.
* Have normal visual fields.
* Be in generally good health based on history, physical examination, electrocardiogram and laboratory findings.
* If female of childbearing potential, use acceptable contraceptive methods. (oral contraceptives (the pill), IUDs, contraceptive implants under the skin, contraceptive rings or patches or injections, diaphragms with spermicide, and condoms with spermicide). Surgical sterilization by tubal ligation or hysterectomy is acceptable

Exclusion Criteria:

* Has current dependence, as determined by the SCID, on any psychoactive substance other than cocaine, alcohol, nicotine, or marijuana or physiologic dependence on alcohol requiring medical detoxification.
* Has any serious medical or psychiatric illness and/or clinically significant abnormal laboratory value, which in the judgment of the Principal Investigator or his/her designee would make study participation unsafe, or would make treatment compliance difficult or put the study staff at undue risk.
* Be under court mandate to obtain treatment.
* Be enrolled in an opiate substitution treatment program within 2 months of randomization.
* Has ever taken vigabatrin in the past.
* Is pregnant or lactating.
* Has clinically significant ophthalmologic disease, which would preclude safety monitoring or is undergoing treatment for ocular disease.
* Has received a drug with known major organ toxicity, including retinotoxicity within 30 days of randomization.
* Is currently participating in, or has been enrolled in another clinical trial within the last 30 days.
* Be anyone who, in the judgment of the investigator, would not be expected to attend regular study visits or to complete the study protocol, due to imminent relocation from the clinic area, legal difficulties, work-related problems, transportation, etc.

Answer: D